Alice B. Gottlieb

Psoriasis is a common, chronic, inflammatory, multisystem disease with predominantly skin and joint manifestations affecting approximately 2% of the population. In this first of 5 sections of the guidelines of care for psoriasis, we discuss the classification of psoriasis; associated comorbidities including autoimmune diseases, cardiovascular risk, psychiatric/psychologic issues, and cancer risk; along with assessment tools for skin disease and quality-of-life issues. Finally, we will discuss the safety and efficacy of the biologic treatments used to treat patients with psoriasis. Psoriasis is a common, chronic, inflammatory, multisystem disease with predominantly skin and joint manifestations affecting approximately 2% of the population. In this first of 5 sections of the guidelines of care for psoriasis, we discuss the classification of psoriasis; associated comorbidities including autoimmune diseases, cardiovascular risk, psychiatric/psychologic issues, and cancer risk; along with assessment tools for skin disease and quality-of-life issues. Finally, we will discuss the safety and efficacy of the biologic treatments used to treat patients with psoriasis. Adherence to these guidelines will not ensure successful treatment in every situation. Furthermore, these guidelines do not purport to establish a legal standard of care and should not be deemed inclusive of all proper methods of care nor exclusive of other methods of care reasonably directed to obtaining the same results. The ultimate judgment regarding the propriety of any specific therapy must be made by the physician and the patient in light of all the circumstances presented by the individual patient. These guidelines address the treatment of both adult and childhood psoriasis and psoriatic arthritis. This document will include the various treatments of psoriasis including topical modalities, ultraviolet (UV) light therapies, systemic agents, and the biologic therapies. In addition, quality of life (QOL) parameters, the type of psoriasis, and the presence of comorbidities such as obesity and other associations of the metabolic syndrome will be reviewed. This guideline will be subdivided into 5 separate documents given the large breadth of material. The first section will give an overview of classification, comorbidities, and assessment tools and cover the biologic treatments for psoriasis. The second section will cover treatments for psoriatic arthritis with an emphasis on the biologics; the third section will cover topical therapies; the fourth section will cover UV light therapy and systemic nonbiologic therapies; and the fifth section will be an overall approach to the treatment of patients with psoriasis with an emphasis on decision-making criteria. It is important, however, for dermatologists to address psoriasis in its entire scope of manifestations. This guideline will not cover the effectiveness of treatments for the less common subtypes of psoriasis, such as guttate, pustular, inverse, and erythrodermic. A work group of recognized psoriasis experts was convened to determine the audience and scope of the guideline, and identify clinical questions to structure the primary issues in diagnosis and management (Table I). Work group members completed a disclosure of commercial support.Table IEight clinical questions used to structure the primary issues in diagnosis and treatment of patients with psoriasisGuideline sectionClinical questionsSection 1• How is psoriasis classified?• What are the potential comorbidities of psoriasis?• What tools are used to measure quality of life in psoriasis and how are these tools used in the treatment of patients?• What are the safety and efficacy of biologic therapies used to treat psoriasis?Section 2• Discuss the classification, prognosis, assessment tools, and systemic therapies used in the treatment of patients with psoriatic arthritis.Section 3• What are the safety and efficacy of topical therapies used to treat psoriasis?Section 4• What are the safety and efficacy of systemic therapies and phototherapies used to treat psoriasis?Section 5• Describe an overall approach to the treatment of patients with psoriasis with an emphasis on decision-making criteria that enable the clinician to individualize therapy based on disease type, extent, response to previous treatments, quality-of-life issues, and comorbidities. Open table in a new tab An evidence-based model was used and evidence was obtained using a search of the MEDLINE database spanning the years 1990 through 2007. Only English-language publications were reviewed. The available evidence was evaluated using a unified system called the Strength of Recommendation Taxonomy developed by editors of the US family medicine and primary care journals (ie, American Family Physician, Family Medicine, Journal of Family Practice, and BMJ USA). This strategy was supported by a decision of the Clinical Guidelines Task Force in 2005 with some minor modifications for a consistent approach to rating the strength of the evidence of scientific studies.1Ebell M.H. Siwek J. Weiss B.D. Woolf S.H. Susman J.L. Ewigman B. et al.Simplifying the language of evidence to improve patient care: strength of recommendation taxonomy (SORT); a patient-centered approach to grading evidence in medical literature.J Fam Pract. 2004; 53: 111-120PubMed Google Scholar Evidence was graded using a 3-point scale based on the quality of methodology as follows:I.Good-quality patient-oriented evidence.II.Limited-quality patient-oriented evidence.III.Other evidence including consensus guidelines, opinion, or case studies. Clinical recommendations were developed on the best available evidence tabled in the guideline. These are ranked as follows:A.Recommendation based on consistent and good-quality patient-oriented evidence.B.Recommendation based on inconsistent or limited-quality patient-oriented evidence.C.Recommendation based on consensus, opinion, or case studies. Prior guidelines on psoriasis were also evaluated.2Committee on Guidelines of Care: Task Force on Psoriasis. Guidelines of care for psoriasis.J Am Acad Dermatol. 1993; 28: 632-637Abstract Full Text PDF PubMed Google Scholar, 3Smith C.H. Anstey A.V. Barker J.N. Burden A.D. Chalmers R.J. Chandler D. et al.British Association of Dermatologists guidelines for use of biological interventions in psoriasis 2005.Br J Dermatol. 2005; 153: 486-497Crossref PubMed Scopus (206) Google Scholar This guideline has been developed in accordance with the American Academy of Dermatology (AAD)/AAD Association “Administrative Regulations for Evidence-based Clinical Practice Guidelines,” which include the opportunity for review and comment by the entire AAD membership and final review and approval by the AAD Board of Directors. Psoriasis vulgaris is a genetic, systemic, inflammatory, chronic disorder, which can be altered by environmental factors. It may be associated with other inflammatory disorders such as psoriatic arthritis, inflammatory bowel disease, and coronary artery disease. It is characterized by scaly, erythematous patches, papules, and plaques that are often pruritic.

Inflammatory cytokines such as tumor necrosis factor (TNF) have been implicated in the pathogenesis of psoriasis. We evaluated the safety and efficacy of etanercept, a TNF antagonist, for the treatment of plaque psoriasis.

Background Psoriasis has substantial psychological and emotional effects. We assessed the effect of etanercept, an effective treatment for the clinical symptoms of psoriasis, on fatigue and symptoms of depression associated with the condition. Methods 618 patients with moderate to severe psoriasis received double-blind treatment with placebo or 50 mg twice-weekly etanercept. The primary efficacy endpoint was a 75% or greater improvement from baseline in psoriasis area and severity index score (PASI 75) at week 12. Secondary and other endpoints included the functional assessment of chronic illness therapy fatigue (FACIT-F) scale, the Hamilton rating scale for depression (Ham-D), the Beck depression inventory (BDI), and adverse events. Efficacy analyses were based on the allocated treatment. Analyses and summaries of safety data were based on the actual treatment received. This study is registered with ClinicalTrials.gov with the identifier NCT00111449. Findings 47% (147 of 311) of patients achieved PASI 75 at week 12, compared with 5% (15 of 306) of those receiving placebo (p<0·0001; difference 42%, 95% CI 36–48). Greater proportions of patients receiving etanercept had at least a 50% improvement in Ham-D or BDI at week 12 compared with the placebo group; patients treated with etanercept also had significant and clinically meaningful improvements in fatigue (mean FACIT-F improvement 5·0 vs 1·9; p<0·0001, difference 3·0, 95% CI 1·6–4·5). Improvements in fatigue were correlated with decreasing joint pain, whereas improvements in symptoms of depression were less correlated with objective measures of skin clearance or joint pain. Interpretation Etanercept treatment might relieve fatigue and symptoms of depression associated with this chronic disease.

Interleukin 17A is a proinflammatory cytokine that is implicated in the pathogenesis of psoriatic arthritis. We assessed the efficacy and safety of subcutaneous secukinumab, a human anti-interleukin-17A monoclonal antibody, in patients with psoriatic arthritis.In this phase 3, double-blind, placebo-controlled study undertaken at 76 centres in Asia, Australia, Canada, Europe, and the USA, adults (aged ≥18 years old) with active psoriatic arthritis were randomly allocated in a 1:1:1:1 ratio with computer-generated blocks to receive subcutaneous placebo or secukinumab 300 mg, 150 mg, or 75 mg once a week from baseline and then every 4 weeks from week 4. Patients and investigators were masked to treatment assignment. The primary endpoint was the proportion of patients achieving at least 20% improvement in the American College of Rheumatology response criteria (ACR20) at week 24. Analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT01752634.Between April 14, and Nov 25, 2013, 397 patients were randomly assigned to receive secukinumab 300 mg (n=100), 150 mg (n=100), 75 mg (n=99), or placebo (n=98). A significantly higher proportion of patients achieved an ACR20 at week 24 with secukinumab 300 mg (54 [54%] patients; odds ratio versus placebo 6·81, 95% CI 3·42-13·56; p<0·0001), 150 mg (51 [51%] patients; 6·52, 3·25-13·08; p<0·0001), and 75 mg (29 [29%] patients; 2·32, 1·14-4·73; p=0·0399) versus placebo (15 [15%] patients). Up to week 16, the most common adverse events were upper respiratory tract infections (four [4%], eight [8%], ten [10%], and seven [7%] with secukinumab 300 mg, 150 mg, 75 mg, and placebo, respectively) and nasopharyngitis (six [6%], four [4%], six [6%], and eight [8%], respectively). Serious adverse events were reported by five (5%), one (1%), and four (4%) patients in the secukinumab 300 mg, 150 mg, and 75 mg groups, respectively, compared with two (2%) in the placebo group. No deaths were reported.Subcutaneous secukinumab 300 mg and 150 mg improved the signs and symptoms of psoriatic arthritis, suggesting that secukinumab is a potential future treatment option for patients with this disorder.Novartis.

Objective To update the 2009 Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) treatment recommendations for the spectrum of manifestations affecting patients with psoriatic arthritis (PsA). Methods GRAPPA rheumatologists, dermatologists, and PsA patients drafted overarching principles for the management of PsA, based on consensus achieved at face‐to‐face meetings and via online surveys. We conducted literature reviews regarding treatment for the key domains of PsA (arthritis, spondylitis, enthesitis, dactylitis, skin disease, and nail disease) and convened a new group to identify pertinent comorbidities and their effect on treatment. Finally, we drafted treatment recommendations for each of the clinical manifestations and assessed the level of agreement for the overarching principles and treatment recommendations among GRAPPA members, using an online questionnaire. Results Six overarching principles had ≥80% agreement among both health care professionals (n = 135) and patient research partners (n = 10). We developed treatment recommendations and a schema incorporating these principles for arthritis, spondylitis, enthesitis, dactylitis, skin disease, nail disease, and comorbidities in the setting of PsA, using the Grading of Recommendations, Assessment, Development and Evaluation process. Agreement of &gt;80% was reached for approval of the individual recommendations and the overall schema. Conclusion We present overarching principles and updated treatment recommendations for the key manifestations of PsA, including related comorbidities, based on a literature review and consensus of GRAPPA members (rheumatologists, dermatologists, other health care providers, and patient research partners). Further updates are anticipated as the therapeutic landscape in PsA evolves.

Background Many patients with psoriasis develop psoriatic arthritis, a chronic inflammatory disease that afflicts peripheral synovial, axial, and entheseal structures. The fully human monoclonal antibody ustekinumab is an efficacious treatment for moderate-to-severe plaque psoriasis. We did a randomised, placebo-controlled, phase 3 trial to assess the safety and efficacy of ustekinumab in patients with active psoriatic arthritis. Methods In this phase 3, multicentre, double-blind, placebo-controlled trial at 104 sites in Europe, North America, and Asia-Pacific, adults with active psoriatic arthritis (≥5 tender and ≥5 swollen joints, C-reactive protein ≥3·0 mg/L) were randomly assigned (1:1:1, by dynamic central randomisation based on an algorithm implemented by an interactive voice–web response system) to 45 mg ustekinumab, 90 mg ustekinumab, or placebo at week 0, week 4, and every 12 weeks thereafter. At week 16, patients with less than 5% improvement in both tender and swollen joint counts entered masked early-escape and were given 45 mg ustekinumab (if in the placebo group) or 90 mg ustekinumab (if in the 45 mg group). At week 24, all remaining patients in the placebo group received ustekinumab 45 mg, which they continued at week 28 and every 12 weeks thereafter. Our primary endpoint was 20% or greater improvement in American College of Rheumatology (ACR20) criteria at week 24. This trial is registered with ClinicalTrials.gov (NCT01009086) and EudraCT (2009-012264-14). Findings Between Nov 30, 2009, and March 30, 2011, 615 patients were randomly assigned—206 to placebo, 205 to 45 mg ustekinumab, and 204 to 90 mg ustekinumab. More ustekinumab-treated (87 of 205 [42·4%] in the 45 mg group and 101 of 204 [49·5%] in the 90 mg group) than placebo-treated (47 of 206 [22·8%]) patients achieved ACR20 at week 24 (p<0·0001 for both comparisons); responses were maintained at week 52. At week 16, proportions of patients with adverse events were similar in the ustekinumab and placebo groups (171 of 409 [41·8%] vs 86 of 205 [42·0%]). Interpretation Ustekinumab significantly improved active psoriatic arthritis compared with placebo, and might offer an alternative therapeutic mechanism of action to approved biological treatments. Funding Janssen Research & Development.

Psoriasis is a chronic, immune-mediated disorder with cutaneous and systemic manifestations and substantial negative effects on patient quality of life. Psoriasis has a strong, albeit polygenic, genetic basis. Whereas approximately half of the accountable genetic effect of psoriasis maps to the major histocompatibility complex, >70 other loci have been identified, many of which implicate nuclear factor-κB, interferon signalling and the IL-23–IL-23 receptor axis. Psoriasis pathophysiology is characterized by abnormal keratinocyte proliferation and immune cell infiltration in the dermis and epidermis involving the innate and adaptive immune systems, with important roles for dendritic cells and T cells, among other cells. Frequent comorbidities are rheumatological and cardiovascular in nature, in particular, psoriatic arthritis. Current treatments for psoriasis include topical agents, photo-based therapies, traditional systemic drugs and biologic agents. Treatments can be used in combination or as monotherapy. Biologic therapies that target specific disease mediators have become a mainstay in the treatment of moderate-to-severe disease, whereas advances in the treatment of mild-to-moderate disease have been limited. Psoriasis is a chronic, immune-mediated disease that can severely affect patient quality of life. Various kinds of skin manifestations are possible; psoriatic arthritis is a common but underdiagnosed comorbidity. Treatments for psoriasis include topical agents, phototherapy and systemic and biologic agents.

<h3>Objective</h3> Assess ustekinumab efficacy (week 24/week 52) and safety (week 16/week 24/week 60) in patients with active psoriatic arthritis (PsA) despite treatment with conventional and/or biological anti-tumour necrosis factor (TNF) agents. <h3>Methods</h3> In this phase 3, multicentre, placebo-controlled trial, 312 adults with active PsA were randomised (stratified by site, weight (≤100 kg/&gt;100 kg), methotrexate use) to ustekinumab 45 mg or 90 mg at week 0, week 4, q12 weeks or placebo at week 0, week 4, week 16 and crossover to ustekinumab 45 mg at week 24, week 28 and week 40. At week 16, patients with &lt;5% improvement in tender/swollen joint counts entered blinded early escape (placebo→45 mg, 45 mg→90 mg, 90 mg→90 mg). The primary endpoint was ≥20% improvement in American College of Rheumatology (ACR20) criteria at week 24. Secondary endpoints included week 24 Health Assessment Questionnaire-Disability Index (HAQ-DI) improvement, ACR50, ACR70 and ≥75% improvement in Psoriasis Area and Severity Index (PASI75). Efficacy was assessed in all patients, anti-TNF-naïve (n=132) patients and anti-TNF-experienced (n=180) patients. <h3>Results</h3> More ustekinumab-treated (43.8% combined) than placebo-treated (20.2%) patients achieved ACR20 at week 24 (p&lt;0.001). Significant treatment differences were observed for week 24 HAQ-DI improvement (p&lt;0.001), ACR50 (p≤0.05) and PASI75 (p&lt;0.001); all benefits were sustained through week 52. Among patients previously treated with ≥1 TNF inhibitor, sustained ustekinumab efficacy was also observed (week 24 combined vs placebo: ACR20 35.6% vs 14.5%, PASI75 47.1% vs 2.0%, median HAQ-DI change −0.13 vs 0.0; week 52 ustekinumab-treated: ACR20 38.9%, PASI75 43.4%, median HAQ-DI change −0.13). No unexpected adverse events were observed through week 60. <h3>Conclusions</h3> The interleukin-12/23 inhibitor ustekinumab (45/90 mg q12 weeks) yielded significant and sustained improvements in PsA signs/symptoms in a diverse population of patients with active PsA, including anti-TNF-experienced PsA patients.

Psoriasis is a chronic, inflammatory multisystem disease that affects up to 3.2% of the US population. This guideline addresses important clinical questions that arise in psoriasis management and care, providing recommendations based on the available evidence. The treatment of psoriasis with biologic agents will be reviewed, emphasizing treatment recommendations and the role of the dermatologist in monitoring and educating patients regarding benefits as well as associated risks. Psoriasis is a chronic, inflammatory multisystem disease that affects up to 3.2% of the US population. This guideline addresses important clinical questions that arise in psoriasis management and care, providing recommendations based on the available evidence. The treatment of psoriasis with biologic agents will be reviewed, emphasizing treatment recommendations and the role of the dermatologist in monitoring and educating patients regarding benefits as well as associated risks. The information presented here represents the authors disclosed relationship with industry during guideline development. Authors (listed alphabetically) with relevant conflicts with respect to this guideline are noted with an asterisk. In accordance with American Academy of Dermatology (AAD) policy, a minimum 51% of work group (WG) members did not have any relevant conflicts of interest. Participation in 1 or more of the activities listed here constitute a relevant conflict:•Service as a member of a speaker bureau, consultant, or advisory board, for pharmaceutical companies on psoriasis disease state or psoriasis drugs that are in development or US Food and Drug Administration (FDA)-approved.•Sponsored research funding or investigator-initiated studies (with partial or full funding from pharmaceutical companies) on psoriasis disease state or psoriasis drugs that are in development or FDA-approved. If a potential conflict was noted, the WG member recused himself or herself from discussion and drafting of recommendations pertinent to the topic area of interest. Complete group consensus was obtained for draft recommendations. Areas in which complete consensus was not achieved, are shown transparently in the guideline. April W. Armstrong, MD, MPH,* served as a consultant for AbbVie, Bristol-Myers Squibb, Celgene Corporation, Genzyme Corporation, GlaxoSmithKline, Janssen-Ortho Inc, Janssen Pharmaceuticals, Inc, Leo Pharma, Inc, Menlo Therapeutics, Modernizing Medicine, Ortho Dermatologics, Pfizer, Inc, Regeneron, Sanofi, and Science 37, Inc, receiving honoraria; as a speaker for AbbVie, Eli Lilly and Company, Janssen Pharmaceuticals, Inc, Regeneron Pharmaceuticals, Inc, and Sanofi receiving honoraria; as a speaker and/or faculty educator for AbbVie, Eli Lilly and Company, and Janssen Pharmaceuticals, Inc, receiving honoraria; as a principal investigator and/or investigator for Amgen, Celgene, Dermira, Eli Lilly and Company, Janssen-Ortho, Inc, Leo Pharma, Inc, National Institutes of Health, Novartis, Regeneron, and UCB receiving grants and/or research funding; as an investigator for Regeneron and Sanofi receiving no compensation; as an advisory board member for AbbVie, Amgen, Janssen-Ortho Inc, Merck & Co, Inc, Novartis, Pfizer, Inc, and UCB receiving honoraria; and as a data safety member for Boehringer Ingelheim receiving honoraria. Cody Connor, MD has no conflicts of interest to disclose. Kelly M. Cordoro, MD,* served as a consultant for Valeant receiving honoraria; as a consultant for Pfizer, Inc, receiving fees; as an advisory board member for Anacor Pharmaceuticals, Inc, receiving honoraria; and in another position as a member of the Scientific Steering Committee for Celgene receiving fees. Dawn M.R. Davis, MD, served as an investigator for Regeneron receiving no compensation. Boni E. Elewski, MD,* served as a consultant for Boehringer Ingelheim, Celgene Corporation, IntendisGmBH, Lilly ICOS LLC, Merz Pharmaceuticals LLC, Novan, Novartis Pharmaceuticals Corp, Pfizer, Inc, Sun Pharmaceutical Industries, Ltd, and Valeant Pharmaceuticals International receiving honoraria; as a principal investigator for AbbVie, Amgen, Boehringer Ingelheim, Celgene Corporation, Eli Lilly and Company, Incyte Corporation, Janssen-Ortho Inc, LEO Pharma, Merck & Co, Inc, Novan, Novartis Pharmaceuticals Corp, Pfizer, Inc, Sun Pharmaceuticals, Ltd, Valeant Pharmaceuticals International, and Vioment receiving grants and/or research funding; as an advisory board member for LEO Pharma receiving honoraria; and in another role for Hoffman-La Roche, Ltd, receiving fees. Craig A. Elmets, MD, served as a consultant for Ferndale Laboratories, Inc, receiving honoraria; as a consultant for Vaxin receiving stock and/or stock options; as a consultant/advisory board member for Vertex Pharmaceuticals receiving fees/honoraria; as a principal investigator for the California Association of Winegrape Growers, Kyowa Hakko USA, and Solgenix LLC receiving grants and/or research funding; as an investigator for Elorac, Inc, Idera Pharmaceuticals, Inc, Kyowa Hakko USA, and Solgenix LLC receiving grants and/or research funding; as a data safety monitoring board member for Astellas Pharma US, Inc, and LEO Laboratories, Ltd, receiving fees; as a stockholder for Medgenics, Inc, receiving no fees; and as a stockholder for Aevi Genomic Medicine (receiving stock) and Immunogen (paid to spouse). Joel M. Gelfand, MD, MSCE,* served as a consultant for AbbVie, Boehringer Ingelheim, Dermira, Dr Reddy, GlaxoSmithKline, Janssen Pharmaceuticals, Inc, Menlo Therapeutics, Novartis Pharmaceuticals Corp, Pfizer, Inc, Regeneron, Sanofi US Services, and Valeant Pharmaceuticals North America LLC receiving honoraria; as a consultant for BMS receiving fees; as a speaker for the American Academy of Dermatology receiving honoraria; as a speaker and/or faculty educator for CME supported by Eli Lilly and Company receiving fees; as a principal investigator for AbbVie, Celgene, Eli Lilly and Company, Janssen Pharmaceuticals, Inc, Novartis Pharmaceuticals Corp, Ortho Dermatologics, Pfizer, Inc, Regeneron, and Sanofi/Sanofi US Services receiving grants and/or research funding; as an investigator for Sanofi receiving grants and/or research funding; as an advisory board member for Sanofi US Services receiving honoraria; as a data safety monitoring board member for Coherus Biosciences and Merck & Co, Inc, receiving honoraria; in another role for the Society for Investigative Dermatology receiving honoraria; in another role for Elsevier, Inc, and SID receiving no compensation; and in another role for Eli Lilly and Company and UCB receiving fees. Kenneth B. Gordon, MD,* served as a consultant for AbbVie, Almirall, Amgen, Boehringer Ingelheim, Bristol-Myers Squibb, Demira, Dermavant Sciences, Kyowa Hakko Kirin Pharma, Inc, Leo Pharma, Ortho Dermatologics, Sun Pharmaceuticals, Ltd, and UCB receiving honoraria; as a consultant for Genzyme receiving fees; as a principal investigator for AbbVie, Amgen, Boehringer Ingelheim, Celgene Corporation, Eli Lilly and Company, Janssen Pharmaceuticals, Inc, Merck & Co, Inc, and Novartis Pharmaceuticals Corp receiving grants and/or research funding; and as an advisory board member for Celgene Corporation, Janssen Pharmaceuticals Inc, Lilly ICOS LLC, Novartis Pharmaceuticals Corp, and Pfizer, Inc, receiving honoraria. Alice B. Gottlieb, MD, PhD,* served as a consultant for Abbott Laboratories, AbbVie, Akros Pharma, Inc, Allergan, Amgen, Amicus Therapeutics, Baxalta Incorporated, Bristol-Myers Squibb, Canfite, Celgene Corporation, CSL Behring, Dermira, Dr Reddy, DUSA Pharmaceuticals, Inc, GlaxoSmithKline, Incyte Corporation, KPI Therapeutics, Lilly ICOS LLC, Meiji Seika Pharma Co, Ltd, Merck & Co, Inc, Mitsubishi Pharma, Novartis Pharmaceuticals Corp, Sanofi-Aventis, Sienna Biopharmaceuticals, Sun Pharmaceutical Industries, Takeda Pharmaceuticals USA, Inc, Teva, UCB, Valeant Pharmaceuticals International, Valeant Pharmaceuticals North America LLC, XBiotech, and Xenoport, Inc, receiving honoraria; as a consultant for Aclaris Therapeutics, Inc, Merck & Co Inc, and XBiotech receiving no compensation; as a speaker for AbbVie, Eli Lilly and Company, and Janssen Biotech receiving honoraria; as a principal investigator for Abbott Laboratories, AbbVie, Allergan, Amgen, Celgene Corporation, Coronado Biosciences, Immune Control, Incyte Corporation, Janssen-Ortho, Inc, LEO Pharma, Lerner Medical Devices, Inc, Lilly ICOS LLC, Merck & Co, Inc, Novartis Pharmaceuticals Corp, Novo Nordisk A/S, Pfizer Inc, UCB, Xbiotech, and Xenoport, Inc, receiving grants and/or research funding; as a principal investigator for Janssen-Ortho, Inc, receiving honoraria; as an advisory board member for Abbott Laboratories, Actelion, Amgen, Astellas Pharma US, Inc, Beiersdorf, Inc., BMS, Celgene Corporation, Coronado Biosciences, Dermira, Genentech, Janssen-Ortho, Inc, Leo Pharma US, Lilly ICOS LLC, Novartis Pharmaceuticals Corp, Novo Nordisk A/S, Pfizer, Inc, and UCB receiving honoraria; in another role for Amgen receiving grants and/or research funding; in another role for Crescendo Bioscience and Karyopharm Therapeutics receiving no compensation; in another role (data safety) for Catabasis Pharmaceuticals, Inc, receiving honoraria; and in another role for DermiPsor receiving honoraria. Daniel H. Kaplan, MD, PhD, served as a consultant for Eli Lilly and Company receiving no compensation and as a member of the data safety monitoring board for Hapten Pharma receiving fees. Arthur Kavanaugh, MD,* served as a principal investigator for AbbVie, Amgen, BMS, Celgene Corporation, Eli Lilly and Company, Janssen Biotech, Novartis, Pfizer, Inc, and UCB receiving grants and/or research funding. Dario Kivelevitch, MD has a first-degree relative employed by GlaxoSmithKline and Boehringer Ingelheim. Matthew Kiselica has no conflicts of interest to disclose. Neil J. Korman*, MD, PhD,* served as a consultant for Novartis Pharmaceuticals Corp receiving honoraria; as a consultant for Dr Reddy's Laboratory receiving fees; as a speaker for AbbVie, Eli Lilly and Company, Janssen, Novartis and Regeneron receiving honoraria; as a principal investigator for AbbVie, Amgen, Celgene Corporation, Dermira, Eli Lilly and Company, Kyowa Hakko Kirin Pharma, Inc, LEO Pharma, Menlo Therapeutics, Pfizer, Prothena, Regeneron, Rhizen, Inc, Syntimmune, and UCB receiving grants and/or research funding; as an advisory board member for Amgen, Celgene Corporation, Eli Lilly and Company, Genentech, GlaxoSmithKline, Janssen Pharmaceuticals, Inc, Novartis Pharmaceuticals Corp, Pfizer, Inc, and Principia Biopharma receiving honoraria; as an advisory board member for Immune, Regeneron, Sun Pharma, and Valeant receiving fees; as an advisory board member/consultant for AbbVie, Eli Lilly, GlaxoSmithKline, Pfizer Inc., and Principa receiving honoraria/fees; and in another role for Janssen Pharmaceuticals, Inc, receiving grants and/or research funding. Daniela Kroshinsky, MD, MPH, FAAD has no conflicts of interest to disclose. Mark Lebwohl, MD,* served as a consultant for Allergan, Aqua, Arcutis, Inc, Boehringer Ingelheim, Bristol-Myers Squibb, Leo Pharma, Menlo Therapeutics, Mitsubishi Pharma/Neuroderm LTD, Promious/Dr. Reddy, Theravance Biopharma, and Verrica Pharmaceuticals Inc receiving honoraria; as a principal investigator for AbbVie, Amgen, Boehringer Ingelheim, Celgene Corporation, Eli Lilly and Company, Incyte Corporation, Janssen Research and Development LLC/Johnson & Johnson, Kadmon Corporation LLC, Leo Pharma, MedImmune/Astra Zeneca, Novartis Pharmaceuticals Corp, Ortho-Dermatologics, Pfizer, Inc, SCIDerm, UCB, and ViDac Pharma receiving grants and/or research funding; and in another role for Corrona, Inc, Facilitation of International Dermatology Education, and the Foundation for Research and Education in Dermatology receiving honoraria. Craig L. Leonardi, MD,* served as a consultant for Celgene Corporation and Dermira receiving honoraria; as a speaker for AbbVie, Amgen, Celgene Corporation, Eli Lilly and Company, Novartis, and Sun Pharmaceuticals, Ltd, receiving honoraria; as a principal investigator for Actavis, Amgen, Boehringer Ingelheim, Celgene Corporation, Cellceutix, Coherus Biosciences, Corrona, Dermira, Eli Lilly and Company, Galderma Laboratories, LP, Glenmark Generics, Inc, Janssen Pharmaceuticals, Inc, Leo Pharma, Inc, Novartis, Novella, Pfizer, Inc, Sandoz (a Novartis company), Sienna Biopharmaceuticals, Stiefel a GSK company, UCB, and Warner Chillcott receiving other financial benefits; and as an advisory board member for AbbVie, Amgen, Boehringer Ingelheim, Eli Lilly and Company, Janssen Pharmaceuticals, Inc, Leo Pharma A/S, Ortho Dermatologics, Pfizer, Inc, Sandoz (a Novartis company), and UCB receiving honoraria. Jason Lichten, MD has no conflicts of interest to disclose. Henry W. Lim, MD, served as a principal or coinvestigator for Estee Lauder, Ferndale Laboratories, Inc, Incyte, and Unigen receiving grants and/or research funding; and as a speaker and/or faculty educator for Pierre Fabre Dermatologie receiving honoraria. Nehal N. Mehta, MD, MSCE,* is a full-time US government employee and has served as a consultant for Amgen, Eli Lilly, and Leo Pharma receiving grants/other payments; as a principal investigator and/or investigator for AbbVie, Celgene, Janssen Pharmaceuticals, Inc, and Novartis receiving grants and/or research funding; and as a principal investigator for the National Institute of Health receiving grants and/or research funding. Alan Menter, MD,* served as a consultant for Abbott Labs, AbbVie, Amgen, Eli Lilly and Company, Galderma USA, Janssen Pharmaceuticals Inc, LEO Pharma US, Menlo Therapeutics, Novartis, Sienna Biopharmaceuticals, and Wyeth Labs receiving honoraria; as a consultant for New Enterprise Associates, Promius Pharma LLC, Spherix Global Insights US, UCB, and Valeant Pharmaceuticals North America receiving fees; as a consultant for Afecta Pharmaceuticals receiving no compensation; as a speaker for Abbott Labs, AbbVie, Amgen, Janssen Biotech, LEO Pharma, US, Pfizer, Inc, Promius Pharma LLC, Sienna Pharmaceuticals, UCB, and Wyeth Labs receiving honoraria; as a principal investigator for AbbVie, Amgen, Boehringer Ingelheim, Celgene Corporation, Eli Lilly and Company, Janssen Pharmaceuticals, Inc, Medimetriks Pharmaceuticals, Inc, Merck & Co, Inc, Novartis Pharmaceutical Corp, and Pfizer, Inc, receiving grant and/or research funding; as an investigator for Eli Lilly and Company and UCB receiving honoraria; investigator for Abbott Labs, Leo Pharma US, and Sienna Biopharmaceutical receiving grants; as an advisory board member for Abbott Labs, AbbVie, Boehringer Ingelheim, Eli Lilly and Company, Janssen Pharmaceuticals, Inc, LEO Pharma US, Medscape, Pfizer, Inc, and Sienna Biopharmaceuticals, receiving honoraria; as an advisory board member for Amgen receiving grant and/or research funding; as an advisory board member for Afecta Pharmaceuticals receiving no compensation; and as an independent contractor for Prime Education receiving fees. Amy Paller, MD,* served as a consultant for Amgen, Amicus Therapeutics, Anacor Pharmaceuticals, Inc, Aqua Pharmaceuticals, BridgeBio Pharma, Castle Creek Pharma, Celgene Corporation, Dermira, Eli Lilly and Company, Galderma Laboratories, LP, Genentech, Menlo Therapeutics, Novartis Pharmaceuticals Corp, Pfizer Inc, Pierre Fabre Dermatologie, Proctor and Gamble, Regeneron, Sanofi, Scioderm, Shire, Sol-Gel Technologies, Stiefel (a GSK company), UCB, and Valeant Pharmaceuticals North America LLC receiving honoraria; as a speaker/educator for Expanscience receiving honoraria; as a principal investigator for AbbVie, Amgen, Anacor Pharmaceuticals, Inc., AnaptysBio, Celgene Corporation, Eli Lilly, Galderma, Janssen Pharmaceuticals, Inc., Leo Pharma, Regeneron and Scioderm receiving no compensation. Sylvia L. Parra, MD, FAAD has no conflicts of interest to disclose. Arun L. Pathy, MD, FAAD has no conflicts of interest to disclose. Elizabeth Farley Prater, MD, FAAD has no conflicts of interest to disclose. Reena Rupani, MD, served as speaker for Nutrafol receiving no compensation. Michael Siegel, PhD has no conflicts of interest to disclose. Benjamin Stoff, MD, MA, served as an investigator for Celtaxsys, Inc, receiving fees. Bruce E. Strober, MD, PhD,* served as a consultant for AbbVie, Almirall, Amgen, Boehringer Ingelheim, Celgene Corporation, Dermira, Eli Lilly and Company, GlaxoSmithKline, Janssen-Ortho, Inc, Leo Pharma, Inc, Maruho Co, Ltd, Medac Pharma, Inc, Menlo Therapeutics, Novartis Pharmaceuticals Corp, Ortho Dermatologics, Pfizer, Inc, Sanofi-Regeneron, Sun Pharmaceuticals Industries, and UCB receiving honoraria; as a consultant for Affibody, Bristol-Myers Squibb, Meiji Seika Pharma Co, Ltd, and UCB receiving fees; as a principal investigator for AbbVie, Amgen, Boehringer Ingelheim, Celgene Corporation, Eli Lilly and Company, Janssen-Ortho, Inc, Merck & Co, Pfizer, Inc, and Sun Pharmaceutical Industries receiving no compensation; as a principal investigator for Galderma Research & Development, LLC receiving grants and/or research funding; as an advisory board member for AbbVie, Amgen, Bristol-Myers Squibb, Celgene Corporation, Dermira, Eli Lilly and Company, Janssen-Ortho, Inc, Novartis Pharmaceuticals Corp, Pfizer, Inc, Sanofi-Regeneron, Sun Pharmaceuticals Industries, and UCB receiving honoraria; as a consultant/advisory board for AstraZeneca Pharmaceuticals LP receiving fees/honoraria; and in another role for AbbVie and Janssen-Ortho, Inc, receiving no compensation. Emily B. Wong, MD, FAAD has no conflicts of interest to disclose. Jashin J. Wu,* MD, served as a consultant for Abbvie, Almirall, Allergan, Amgen, Bristol-Myers Squibb, Celgene, Dermira, Dr Reddy's Laboratories, Eli Lilly and Company, Janssen Biotech, LEO Pharma, Novartis, Ortho Dermatologics, Pfizer, Inc, Promius Pharma, Regeneron, Sun Pharmaceutical Industries, Ltd, UCB, and Valeant Pharmaceuticals North America, LLC receiving fees and and/or or honoraria; as a speaker for AbbVie, Celgene, Novartis, Regeneron, Sun Pharmaceutical Industries Ltd, UCB, and Valeant Pharmaceuticals North America LLC receiving honoraria; and as a principal and/or investigator for AbbVie, AstraZeneca, Boehringer Ingelheim, Coherus Biosciences, Dermira, Eli Lilly and Company, Janssen Pharmaceuticals, Inc, Merck & Co, Inc, Novartis, Pfizer, Inc, Regeneron, Sandoz (a Novartis company), and Sun Pharmaceutical Industries, Ltd, receiving research and/or grant funding. Vidhya Hariharan, PhD, has no conflicts of interest to disclose. Adherence to these guidelines will not ensure successful treatment in every situation. Furthermore, these guidelines should not be interpreted as setting a standard of care, nor should they be deemed either inclusive of all proper methods of care or exclusive of other methods of care reasonably directed toward obtaining the same results. The ultimate judgment regarding the propriety of any specific therapy must be made by the physician and the patient in light of all the circumstances presented by the individual patient and the known variability and biologic behavior of the disease. Furthermore, the treatment dosages used in clinical trials may not be effective in certain cases, and some patients may require shorter intervals between doses and/or higher treatment doses of a particular biologic agent. This guideline reflects the best available data at the time the guideline was prepared. The results of future studies will likely require revisions to the recommendations in this guideline to reflect new data. This guideline will cover the use of biologic agents in the treatment of psoriasis in adults; psoriasis in the pediatric population will be covered in the “Guidelines of care for the management and treatment of pediatric psoriasis” guideline. This guideline will not cover the treatment of psoriatic arthritis (PsA) in detail, its management is reviewed in detail by the American College of Rheumatology and National Psoriasis Foundation treatment guidelines.7Kimball A.B. Gladman D. Gelfand J.M. et al.National Psoriasis Foundation clinical consensus on psoriasis comorbidities and recommendations for screening.J Am Acad Dermatol. 2008; 58: 1031-1042Abstract Full Text Full Text PDF PubMed Scopus (315) Google Scholar, 7Kimball A.B. Gladman D. Gelfand J.M. et al.National Psoriasis Foundation clinical consensus on psoriasis comorbidities and recommendations for screening.J Am Acad Dermatol. 2008; 58: 1031-1042Abstract Full Text Full Text PDF PubMed Scopus (315) Google Scholar A multidisciplinary WG of psoriasis experts consisting of dermatologists (including private practitioners), a rheumatologist, a cardiologist, and representatives from a patient advocacy organization was convened to update and expand on the previously published 2008 AAD psoriasis guideline.1Menter A. Gottlieb A. Feldman S.R. et al.Guidelines of care for the management of psoriasis and psoriatic arthritis: section 1. Overview of psoriasis and guidelines of care for the treatment of psoriasis with biologics.J Am Acad Dermatol. 2008; 58: 826-850Abstract Full Text Full Text PDF PubMed Scopus (882) Google Scholar The WG determined the scope of the guideline and identified important clinical questions with regard to biologic treatment of psoriasis (Table I). WG members completed a disclosure of interests that was periodically updated and reviewed for potential relevant conflicts of interests throughout the guideline development process.Table IClinical questionsWhat are the efficacy, effectiveness, effect of switching, and adverse effects of the following biologic drugs used as monotherapy or in combination with other psoriasis therapies to treat moderate-to-severe psoriasis in adults?•Etanercept (FDA approval on April 30, 2004)•Infliximab (FDA approval on September 27, 2006)•Adalimumab (FDA approval on January 22, 2008)•Certolizumab (FDA approval on May 27, 2018)•Ustekinumab (FDA approval on September 25, 2009)•Secukinumab (FDA approval on January 21, 2015)•Ixekizumab (FDA approval on March 22, 2016)•Brodalumab (FDA approval on February 15, 2017)•Guselkumab (FDA approval on July 13, 2017)•Tildrakizumab (FDA approval on March 21, 2018)•Risankizumab (FDA approval pending)FDA, US Food and Drug Administration. Open table in a new tab FDA, US Food and Drug Administration. An evidence-based model was used, and evidence was obtained by using a search of the PubMed and MEDLINE databases from January 1, 2008, to December 31, 2017, for clinical questions addressed in the previous version of this guideline published in 2008-2011, and for all newly identified clinical questions. Searches were limited to publications in the English language. Medical Subject Heading (MeSH) terms used in various combinations in the literature search included psoriasis (vulgaris, plaque, guttate, erythrodermic, pustular, palmoplantar, inverse, nail), biologic therapy (adalimumab, etanercept, infliximab, secukinumab, ustekinumab, brodalumab, tildrakizumab, guselkumab, risankizumab, tofacitinib), biosimilar, cessation, interruption, failure (primary, secondary), combination therapy, anti–TNF-α inhibitors, interleukin inhibitors, therapy switch/alternate, and superior. After removal of duplicate data, 354 articles were retained for final review based on relevancy and the highest level of available evidence for the outlined clinical questions. Evidence tables were generated for these studies and utilized by the WG in developing recommendations. The Academy's prior published guidelines on psoriasis were evaluated, as were other current published guidelines on psoriasis. The available evidence was evaluated by using a unified system called the Strength of Recommendation Taxonomy, which was developed by editors of the US family medicine and primary care journals (ie, American Family Physician, Family Medicine, Journal of Family Practice, and BMJ USA). Evidence was graded by using a 3-point scale based on the quality of methodology (eg, randomized controlled trial [RCT], case-control study, prospective or retrospective cohort study, case series) and the overall focus of the study (ie, diagnosis; treatment, prevention, and/or screening; or prognosis) as follows:I.Good-quality patient-oriented evidence (ie, evidence measuring outcomes that matter to patients: morbidity, mortality, symptom improvement, cost reduction, and quality of life [QOL]).II.Limited-quality patient-oriented evidence.III.Other evidence including consensus guidelines, opinion, case studies, or disease-oriented evidence (ie, evidence measuring intermediate, physiologic, or surrogate end points that may or may not reflect improvements in patient outcomes). Clinical recommendations were developed on the basis of best available evidence, as summarized in the tables in the guideline. These are ranked as follows:A.Recommendation based on consistent and good-quality patient-oriented evidence.B.Recommendation based on inconsistent or limited-quality patient-oriented evidence.C.Recommendation based on consensus, opinion, case studies, or disease-oriented evidence. In those situations in which documented evidence-based data are not available, we have utilized expert opinion to generate our clinical recommendations or opted not to issue a recommendation. This guideline has been developed in accordance with the American Academy of Dermatology/AAD Association Administrative Regulations for Evidence-Based Clinical Practice Guidelines (May 2014),2American Academy of Dermatology. Evidence-based clinical practice guidelines. Available at: https://www.aad.org/forms/policies/uploads/ar/ar%20evidence-based%20clinical%20practice%20%20guidelines.pdf. Accessed March 1, 2018.Google Scholar which includes the opportunity for review and comment by the entire AAD membership and final review and comment by the AAD Board of Directors. Additionally, this guideline has been developed in collaboration with the National Psoriasis Foundation, and as part of the review process, the National Psoriasis Foundation medical board members provided their feedback. This guideline will be considered current for a period of 5 years from the date of publication unless reaffirmed, updated, or retired before that time. Psoriasis vulgaris is a chronic inflammatory skin disease that classically presents with well-demarcated, red plaques with silvery scale, commonly involving the scalp, elbows, knees, and presacral region, though any area of the skin may be involved, including the palms, soles, nails, and genitalia. Although the severity of psoriasis is defined in part by the total body surface area (BSA) involved, with involvement of less than 3% of BSA considered mild, involvement of 3% to 10% of BSA considered moderate, and involvement of greater than 10% considered severe disease, psoriasis can be severe irrespective of BSA when it has serious emotional consequences or when it occurs in select locations, including but not restricted to, the hands, feet, scalp, face, or genital area, or when it causes intractable pruritus. The Psoriasis Area Severity Index (PASI) is a more specific means of quantifying the extent and severity of psoriasis, as it takes into account not only BSA but also the intensity of redness, scaling, and plaque thickness, ultimately producing a score from 0 (no disease) to 72 (maximal disease severity). The PASI is used for monitoring response to treatments in clinical trials and as a research tool to judge the severity of psoriasis. It is rarely utilized by dermatologists in clinical practice to guide management. Psoriasis is an inflammatory, immune-mediated condition involving cutaneous T cells, dendritic cells, and keratinocytes, with subsequent release of a variety of cytokines and other soluble mediators. These chemical signals are responsible for keratinocyte hyperproliferation manifesting as characteristic scaly plaques, and they also contribute to the augmented inflammation underlying a number of systemic disease associations, including metabolic syndrome, cardiovascular disease, and PsA. To inhibit the inflammation underpinning this condition, a number of topical and systemic medications have been created with varying success. The term biologic agents refers to engineered monoclonal antibodies and fusion proteins that exert their therapeutic actions by blocking specific cytokines or cytokine receptors critical to psoriatic inflammation.

Since some patients with psoriatic arthritis do not respond to typical drug treatments, alternatives are needed. Findings suggest that interleukins 12 and 23 might affect clinical symptoms and pathological joint changes of psoriatic arthritis. Ustekinumab is a human monoclonal antibody that inhibits receptor-binding of these cytokines. We aimed to assess the efficacy and safety of ustekinumab for psoriatic arthritis in this phase II study.We undertook a double-blind, randomised, placebo-controlled, crossover study at 24 sites in North America and Europe. Patients with active psoriatic arthritis were randomly allocated via interactive voice response system to either ustekinumab (90 mg or 63 mg) every week for 4 weeks (weeks 0-3) followed by placebo at weeks 12 and 16 (n=76; Group 1) or placebo (weeks 0-3) and ustekinumab (63 mg) at weeks 12 and 16 (n=70; Group 2). The first 12 weeks of the study were placebo-controlled. Masking was maintained to week 16, and patients were followed up to week 36 [corrected]. The primary endpoint was ACR20 response at week 12. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00267956.At week 12, 32 (42%) patients in Group 1 and ten (14%) in Group 2 achieved the primary endpoint (difference 28% [95% CI 14.0-41.6]; p=0.0002). Of 124 (85%) participants with psoriasis affecting 3% or more body surface area, 33 of 63 (52%) in Group 1 and three of 55 (5%) in Group 2 had a 75% or greater improvement in psoriasis area and severity index score at week 12 (47% [33.2-60.6]; p<0.0001). During the placebo-controlled period (weeks 0-12), adverse events arose in 46 (61%) patients in Group 1 and 44 (63%) in Group 2; serious adverse events were recorded in three (4%) Group 2 patients (none in Group 1).Ustekinumab significantly reduced signs and symptoms of psoriatic arthritis and diminished skin lesions compared with placebo, and the drug was well tolerated. Larger and longer term studies are needed to further characterise ustekinumab efficacy and safety for treatment of psoriatic arthritis.

Background Tumor necrosis factor–α is a key mediator in the pathogenesis of psoriasis. Infliximab is a monoclonal antibody that specifically binds to tumor necrosis factor-α, blocking its biologic activity. Objective The purpose of this study was to access the efficacy and safety of infliximab induction therapy for patients with severe plaque psoriasis. Methods In this multicenter, double-blind, placebo-controlled trial, 249 patients with severe plaque psoriasis were randomly assigned to receive intravenous infusions of either 3 or 5 mg/kg of infliximab or placebo given at weeks 0, 2, and 6. The primary end point was the proportion of patients who achieved at least 75% improvement in Psoriasis Area and Severity Index score from baseline at week 10. At week 26, patients whose Physician Global Assessment indicated moderate or severe disease were eligible for a single intravenous infusion of their assigned treatment to assess the safety of retreatment after a 20-week, treatment-free interval. Results At week 10, 72% of patients treated with infliximab (3 mg/kg) and 88% of patients treated with infliximab (5 mg/kg) achieved a 75% or greater improvement from baseline in Psoriasis Area and Severity Index score compared with 6% of patients treated with placebo (P < .001). Improvement was observed in both infliximab groups as early as 2 weeks. Overall, 63%, 78%, and 79% of patients in the placebo, 3-, and 5-mg/kg groups, respectively, reported one or more adverse events. Conclusions Infliximab treatment resulted in a rapid and significant improvement in the signs and symptoms of psoriasis. Infliximab was generally well tolerated.

Hidradenitis suppurativa is a painful, chronic inflammatory skin disease with few options for effective treatment. In a phase 2 trial, adalimumab, an antibody against tumor necrosis factor α, showed efficacy against hidradenitis suppurativa.

Psoriasis is a common, chronic, inflammatory, multisystem disease with predominantly skin and joint manifestations affecting approximately 2% of the population. In this fourth of 6 sections of the guidelines of care for psoriasis, we discuss the use of traditional systemic medications for the treatment of patients with psoriasis. Treatment should be tailored to meet individual patients' needs. We will discuss in detail the efficacy and safety, and offer recommendations for the use of the 3 most commonly used, and approved, traditional systemic agents: methotrexate, cyclosporine, and acitretin. We will also briefly discuss the available data for the use of azathioprine, fumaric acid esters, hydroxyurea, leflunomide, mycophenolate mofetil, sulfasalazine, tacrolimus, and 6-thioguanine in psoriasis.

Psoriasis is a common, chronic, inflammatory, multisystem disease with predominantly skin and joint manifestations affecting approximately 2% of the population. In this second of 5 sections of the guidelines of care for psoriasis, we give an overview of psoriatic arthritis including its cardinal clinical features, pathogenesis, prognosis, classification, assessment tools used to evaluate psoriatic arthritis, and the approach to treatment. Although patients with mild to moderate psoriatic arthritis may be treated with nonsteroidal anti-inflammatory drugs and/or intra-articular steroid injections, the use of disease-modifying antirheumatic drugs, particularly methotrexate, along with the biologic agents, are considered the standard of care in patients with more significant psoriatic arthritis. We will discuss the use of disease-modifying antirheumatic drugs and the biologic therapies in the treatment of patients with moderate to severe psoriatic arthritis.

Objective: To develop comprehensive recommendations for the treatment of the various clinical manifestations of psoriatic arthritis (PsA) based on evidence obtained from a systematic review of the literature and from consensus opinion. Methods: Formal literature reviews of treatment for the most significant discrete clinical manifestations of PsA (skin and nails, peripheral arthritis, axial disease, dactylitis and enthesitis) were performed and published by members of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA). Treatment recommendations were drafted for each of the clinical manifestations by rheumatologists, dermatologists and PsA patients based on the literature reviews and consensus opinion. The level of agreement for the individual treatment recommendations among GRAPPA members was assessed with an online questionnaire. Results: Treatment recommendations were developed for peripheral arthritis, axial disease, psoriasis, nail disease, dactylitis and enthesitis in the setting of PsA. In rotal, 19 recommendations were drafted, and over 80% agreement was obtained on 16 of them. In addition, a grid that factors disease severity into each of the different disease manifestations was developed to help the clinician with treatment decisions for the individual patient from an evidenced-based perspective. Conclusions: Treatment recommendations for the cardinal physical manifestations of PsA were developed based on a literature review and consensus between rheumatologists and dermatologists. In addition, a grid was established to assist in therapeutic reasoning and decision making for individual patients. It is anticipated that periodic updates will take place using this framework as new data become available.

Previous studies of infliximab in psoriasis have demonstrated rapid improvement with induction therapy and sustained response with regularly administered maintenance therapy.The efficacy and safety of continuous (every-8-week) and intermittent (as-needed) maintenance regimens were compared.Patients with moderate-to-severe psoriasis (n = 835) were randomized to induction therapy (weeks 0, 2, and 6) with infliximab 3 mg/kg or 5 mg/kg or placebo. Infliximab-treated patients were randomized again at week 14 to continuous or intermittent maintenance regimens at their induction dose.At week 10, 75.5% and 70.3% of patients in the infliximab 5 mg/kg and 3 mg/kg groups, respectively, achieved PASI 75; 45.2% and 37.1% achieved PASI 90 (vs 1.9% [PASI 75] and 0.5% [PASI 90] for placebo; P < .001). Through week 50, PASI responses were better maintained with continuous compared with intermittent therapy within each dose, and with 5 mg/kg compared with 3 mg/kg continuous therapy.Longer term (>1 year) maintenance therapy and further study of infliximab serum concentrations over this period, in both PASI 75 responders and non-responders, would be preferable.Through week 50, response was best maintained with continuous infliximab therapy. Infliximab was generally well-tolerated in most patients.

To determine safety and efficacy of monotherapy with etanercept.Randomized, double-blind, placebo-controlled, multicenter study.Outpatient, ambulatory; private practice and university dermatology research centers.Patients aged at least 18 years, with plaque psoriasis involving 10% or more of body surface area; 148 were screened and 112 were randomly assigned to treatment groups and received study drug.Patients received placebo or etanercept, 25 mg, subcutaneously twice a week for 24 weeks. Other psoriasis therapies were limited during the study.Safety measurements included tracking of adverse events and laboratory values. Efficacy was evaluated using the Psoriasis Area and Severity Index (PASI); the primary end point was a 75% improvement in PASI. Other efficacy measurements included patient and physician global assessments and quality-of-life measures.After 12 weeks of treatment, 17 (30%) of the 57 etanercept-treated patients and 1 (2%) of the 55 placebo-treated patients had achieved PASI 75%, and after 24 weeks, 32 (56%) of etanercept-treated patients and 3 (5%) of placebo-treated patients had reached this level (P<.001 for both time points). By 24 weeks, psoriasis was clear or minimal by physician's global assessment in more than 50% of patients who received etanercept. Treatment failure (PASI response <50) occurred in 23% of patients at week 24. All other measures confirmed the efficacy of etanercept. Adverse events were similar among etanercept and placebo groups.Etanercept monotherapy provided significant benefit to patients with psoriasis and had a favorable safety profile.

Psoriasis is a common, chronic, inflammatory, multi-system disease with predominantly skin and joint manifestations affecting approximately 2% of the population. In this third of 6 sections of the guidelines of care for psoriasis, we discuss the use of topical medications for the treatment of psoriasis. The majority of patients with psoriasis have limited disease (<5% body surface area involvement) and can be treated with topical agents, which generally provide a high efficacy-to-safety ratio. Topical agents may also be used adjunctively for patients with more extensive psoriasis undergoing therapy with either ultraviolet light, systemic or biologic medications. However, the use of topical agents as monotherapy in the setting of extensive disease or in the setting of limited, but recalcitrant, disease is not routinely recommended. Treatment should be tailored to meet individual patients' needs. We will discuss the efficacy and safety of as well as offer recommendations for the use of topical corticosteroids, vitamin D analogues, tazarotene, tacrolimus, pimecrolimus, emollients, salicylic acid, anthralin, coal tar, as well as combination therapy.

Psoriasis is a common, chronic, inflammatory, multisystem disease with predominantly skin and joint manifestations affecting approximately 2% of the population. In the first 5 parts of the American Academy of Dermatology Psoriasis Guidelines of Care, we have presented evidence supporting the use of topical treatments, phototherapy, traditional systemic agents, and biological therapies for patients with psoriasis and psoriatic arthritis. In this sixth and final section of the Psoriasis Guidelines of Care, we will present cases to illustrate how to practically use these guidelines in specific clinical scenarios. We will describe the approach to treating patients with psoriasis across the entire spectrum of this fascinating disease from mild to moderate to severe, with and without psoriatic arthritis, based on the 5 prior published guidelines. Although specific therapeutic recommendations are given for each of the cases presented, it is important that treatment be tailored to meet individual patients' needs. In addition, we will update the prior 5 guidelines and address gaps in research and care that currently exist, while making suggestions for further studies that could be performed to help address these limitations in our knowledge base.

The interleukin‐17 cytokine family plays a central role in psoriasis pathogenesis. To evaluate the efficacy and safety of brodalumab, a human anti‐interleukin‐17 receptor antibody, in treating patients with moderate‐to‐severe plaque psoriasis. In this phase III, double‐blind, placebo‐controlled study (NCT01708590; AMAGINE‐1), adult patients in the U.S.A., Canada and Europe were randomized to brodalumab (140 or 210 mg) or placebo every 2 weeks (Q2W), with an additional dose at week 1, for a 12‐week induction phase. At week 12, patients receiving brodalumab who achieved static Physician's Global Assessment 0 or 1 (sPGA success) were rerandomized to the placebo or induction dose. After week 16, patients with sPGA ≥ 3 were re‐treated with the induction dose. After ≥ 12 weeks of retreatment, patients with sPGA 2 for ≥ 4 weeks or sPGA ≥ 3 were rescued with brodalumab 210 mg Q2W. At week 12, patients randomized to brodalumab with sPGA ≥ 2 or placebo received brodalumab 210 mg Q2W. Coprimary end points were the percentage of patients with ≥ 75% improvement in Psoriasis Area and Severity Index score (PASI 75) and sPGA success at week 12. There were 661 patients randomized: 220 placebo, 219 brodalumab 140 mg and 222 brodalumab 210 mg. At week 12, 60% (140 mg) and 83% (210 mg) vs. 3% (placebo) achieved PASI 75, and 54% (140 mg) and 76% (210 mg) vs. 1% (placebo) achieved sPGA success. The safety profile was considered acceptable. Brodalumab therapy resulted in significant clinical benefit and an acceptable safety profile in patients with moderate‐to‐severe plaque psoriasis.

Background Wide-ranging prevalence estimates of psoriatic arthritis (PsA) in patients with psoriasis have been reported. Objectives To assess the prevalence and incidence of PsA in patients with psoriasis. Methods Two authors independently searched 3 databases for studies reporting on the prevalence or incidence of PsA in patients with psoriasis. A proportion meta-analysis was performed to calculate the pooled proportion estimates of PsA in patients with psoriasis. Results A total of 266 studies examining 976,408 patients with psoriasis were included. Overall, the pooled proportion (95% confidence interval [CI]) of PsA among patients with psoriasis was 19.7% (95% CI, 18.5%-20.9%). In children and adolescents (<18 years of age), the pooled prevalence was 3.3% (95% CI, 2.1%-4.9%). The PsA prevalence was 22.7% (95% CI, 20.6%-25.0%) in European patients with psoriasis, 21.5% (95% CI, 15.4%-28.2%) in South American patients with psoriasis, 19.5% (95% CI, 17.1%-22.1%) in North American patients with psoriasis, 15.5% (95% CI, 0.009%-51.5%) in African patients with psoriasis, and 14.0% (95% CI, 95% CI, 11.7%-16.3%) in Asian patients with psoriasis. The prevalence of PsA was 23.8% (95% CI, 20.1%-27.6%) in studies in which the Classification Criteria for Psoriatic Arthritis were applied. The incidence of PsA among patients with psoriasis ranged from 0.27 to 2.7 per 100 person-years. Limitations Between-study heterogeneity may have affected the estimates. Conclusions We found that 1 in 4 patients with psoriasis have PsA. With the growing recognition of the Classification Criteria for Psoriatic Arthritis, more homogenous and comparable prevalence estimates are expected to be reported. Wide-ranging prevalence estimates of psoriatic arthritis (PsA) in patients with psoriasis have been reported. To assess the prevalence and incidence of PsA in patients with psoriasis. Two authors independently searched 3 databases for studies reporting on the prevalence or incidence of PsA in patients with psoriasis. A proportion meta-analysis was performed to calculate the pooled proportion estimates of PsA in patients with psoriasis. A total of 266 studies examining 976,408 patients with psoriasis were included. Overall, the pooled proportion (95% confidence interval [CI]) of PsA among patients with psoriasis was 19.7% (95% CI, 18.5%-20.9%). In children and adolescents (<18 years of age), the pooled prevalence was 3.3% (95% CI, 2.1%-4.9%). The PsA prevalence was 22.7% (95% CI, 20.6%-25.0%) in European patients with psoriasis, 21.5% (95% CI, 15.4%-28.2%) in South American patients with psoriasis, 19.5% (95% CI, 17.1%-22.1%) in North American patients with psoriasis, 15.5% (95% CI, 0.009%-51.5%) in African patients with psoriasis, and 14.0% (95% CI, 95% CI, 11.7%-16.3%) in Asian patients with psoriasis. The prevalence of PsA was 23.8% (95% CI, 20.1%-27.6%) in studies in which the Classification Criteria for Psoriatic Arthritis were applied. The incidence of PsA among patients with psoriasis ranged from 0.27 to 2.7 per 100 person-years. Between-study heterogeneity may have affected the estimates. We found that 1 in 4 patients with psoriasis have PsA. With the growing recognition of the Classification Criteria for Psoriatic Arthritis, more homogenous and comparable prevalence estimates are expected to be reported.

Etanercept, a soluble tumor necrosis factor receptor, has been shown to lessen disease severity in adult patients with psoriasis. We assessed the efficacy and safety of etanercept in children and adolescents with moderate-to-severe plaque psoriasis.

The mechanisms of action of marketed TNF-blocking drugs in lesional tissues are still incompletely understood. Because psoriasis plaques are accessible to repeat biopsy, the effect of TNF/lymphotoxin blockade with etanercept (soluble TNFR) was studied in ten psoriasis patients treated for 6 months. Histological response, inflammatory gene expression, and cellular infiltration in psoriasis plaques were evaluated. There was a rapid and complete reduction of IL-1 and IL-8 (immediate/early genes), followed by progressive reductions in many other inflammation-related genes, and finally somewhat slower reductions in infiltrating myeloid cells (CD11c+ cells) and T lymphocytes. The observed decreases in IL-8, IFN-gamma-inducible protein-10 (CXCL10), and MIP-3alpha (CCL20) mRNA expression may account for decreased infiltration of neutrophils, T cells, and dendritic cells (DCs), respectively. DCs may be less activated with therapy, as suggested by decreased IL-23 mRNA and inducible NO synthase mRNA and protein. Decreases in T cell-inflammatory gene expression (IFN-gamma, STAT-1, granzyme B) and T cell numbers may be due to a reduction in DC-mediated T cell activation. Thus, etanercept-induced TNF/lymphotoxin blockade may break the potentially self-sustaining cycle of DC activation and maturation, subsequent T cell activation, and cytokine, growth factor, and chemokine production by multiple cell types including lymphocytes, neutrophils, DCs, and keratinocytes. This results in reversal of the epidermal hyperplasia and cutaneous inflammation characteristic of psoriatic plaques.

Objective To develop an evidence‐based guideline for the pharmacologic and nonpharmacologic treatment of psoriatic arthritis (PsA), as a collaboration between the American College of Rheumatology ( ACR ) and the National Psoriasis Foundation ( NPF ). Methods We identified critical outcomes in PsA and clinically relevant PICO (population/intervention/comparator/outcomes) questions. A Literature Review Team performed a systematic literature review to summarize evidence supporting the benefits and harms of available pharmacologic and nonpharmacologic therapies for PsA. GRADE (Grading of Recommendations Assessment, Development and Evaluation) methodology was used to rate the quality of the evidence. A voting panel, including rheumatologists, dermatologists, other health professionals, and patients, achieved consensus on the direction and the strength of the recommendations. Results The guideline covers the management of active PsA in patients who are treatment‐naive and those who continue to have active PsA despite treatment, and addresses the use of oral small molecules, tumor necrosis factor inhibitors, interleukin‐12/23 inhibitors ( IL ‐12/23i), IL ‐17 inhibitors, CTLA 4‐Ig (abatacept), and a JAK inhibitor (tofacitinib). We also developed recommendations for psoriatic spondylitis, predominant enthesitis, and treatment in the presence of concomitant inflammatory bowel disease, diabetes, or serious infections. We formulated recommendations for a treat‐to‐target strategy, vaccinations, and nonpharmacologic therapies. Six percent of the recommendations were strong and 94% conditional, indicating the importance of active discussion between the health care provider and the patient to choose the optimal treatment. Conclusion The 2018 ACR / NPF PsA guideline serves as a tool for health care providers and patients in the selection of appropriate therapy in common clinical scenarios. Best treatment decisions consider each individual patient situation. The guideline is not meant to be proscriptive and should not be used to limit treatment options for patients with PsA.

Psoriasis is a common, chronic, inflammatory, multisystem disease with predominantly skin and joint manifestations affecting approximately 2% of the population. In this fifth of 6 sections of the guidelines of care for psoriasis, we discuss the use of ultraviolet (UV) light therapy for the treatment of patients with psoriasis. Treatment should be tailored to meet individual patients' needs. We will discuss in detail the efficacy and safety as well as offer recommendations for the use of phototherapy, including narrowband and broadband UVB and photochemotherapy using psoralen plus UVA, alone and in combination with topical and systemic agents. We will also discuss the available data for the use of the excimer laser in the targeted treatment of psoriasis. Finally, where available, we will summarize the available data that compare the safety and efficacy of the different forms of UV light therapy. Psoriasis is a common, chronic, inflammatory, multisystem disease with predominantly skin and joint manifestations affecting approximately 2% of the population. In this fifth of 6 sections of the guidelines of care for psoriasis, we discuss the use of ultraviolet (UV) light therapy for the treatment of patients with psoriasis. Treatment should be tailored to meet individual patients' needs. We will discuss in detail the efficacy and safety as well as offer recommendations for the use of phototherapy, including narrowband and broadband UVB and photochemotherapy using psoralen plus UVA, alone and in combination with topical and systemic agents. We will also discuss the available data for the use of the excimer laser in the targeted treatment of psoriasis. Finally, where available, we will summarize the available data that compare the safety and efficacy of the different forms of UV light therapy. Adherence to these guidelines will not ensure successful treatment in every situation. Furthermore, these guidelines should not be deemed inclusive of all proper methods of care nor exclusive of other methods of care reasonably directed to obtaining the same results. The ultimate judgment regarding the propriety of any specific therapy must be made by the physician and the patient in light of all the circumstances presented by the individual patient. This fifth section will cover the management and treatment of psoriasis with phototherapy. A work group of recognized psoriasis experts was convened to determine the audience and scope of the guideline, and identify clinical questions to structure the primary issues in diagnosis and management discussed in American Academy of Dermatology (AAD) psoriasis guidelines sections 1 and 2.1Menter A. Gottlieb A. Feldman S.R. Van Voorhees A.S. Leonardi C.L. Gordon K.B. et al.Guidelines of care for the management of psoriasis and psoriatic arthritis: section 1. Overview of psoriasis and guidelines of care for the treatment of psoriasis with biologics.J Am Acad Dermatol. 2008; 58: 826-850Abstract Full Text Full Text PDF PubMed Scopus (940) Google Scholar, 2Gottlieb A. Korman N.J. Gordon K.B. Feldman S.R. Lebwohl M. Koo J.Y. et al.Guidelines of care for the management of psoriasis and psoriatic arthritis: section 2. Psoriatic arthritis: overview and guidelines of care for treatment with an emphasis on the biologics.J Am Acad Dermatol. 2008; 58: 851-864Abstract Full Text Full Text PDF PubMed Scopus (330) Google Scholar Work group members completed a disclosure of commercial support. An evidence-based model was used and evidence was obtained using a search of the MEDLINE database spanning the years 1960 through 2009. Only English-language publications were reviewed. The available evidence was evaluated using a unified system called the Strength of Recommendation Taxonomy developed by editors of the US family medicine and primary care journals (ie, American Family Physician, Family Medicine, Journal of Family Practice, and BMJ USA). This strategy was supported by a decision of the Clinical Guidelines Task Force in 2005 with some minor modifications for a consistent approach to rating the strength of the evidence of scientific studies.3Ebell M.H. Siwek J. Weiss B.D. Woolf S.H. Susman J.L. Ewigman B. et al.Simplifying the language of evidence to improve patient care: strength of recommendation taxonomy (SORT); a patient-centered approach to grading evidence in medical literature.J Fam Pract. 2004; 53: 111-120PubMed Google Scholar Evidence was graded using a 3-point scale based on the quality of methodology as follows:I.Good-quality patient-oriented evidence.II.Limited-quality patient-oriented evidence.III.Other evidence including consensus guidelines, opinion, or case studies. Clinical recommendations were developed on the best available evidence tabled in the guideline. These are ranked as follows:A.Recommendation based on consistent and good-quality patient-oriented evidence.B.Recommendation based on inconsistent or limited-quality patient-oriented evidence.C.Recommendation based on consensus, opinion, or case studies. In those situations where documented evidence-based data are not available, we have used expert opinion to generate our clinical recommendations. Prior guidelines on psoriasis were also evaluated. This guideline has been developed in accordance with the AAD “Administrative Regulations for Evidence-based Clinical Practice Guidelines,” which include the opportunity for review and comment by the entire AAD membership and final review and approval by the AAD Board of Directors. In the past, conventional psoriasis therapies–phototherapy, photochemotherapy, methotrexate, cyclosporine, and acitretin–were used when psoriasis was too extensive for topical therapy. Although a minimum body surface area (eg, 10%) has been traditionally used as a prerequisite to starting ultraviolet (UV) light or systemic therapy for psoriasis, a subset of patients with limited disease have debilitating symptoms. For example, whereas severe psoriasis of the palms and soles or severe scalp psoriasis affects less than 5% of the body surface area, the significant negative effect on the quality of life of the patient makes treatment with systemic therapies an appropriate approach to the management. Although treatment options for psoriasis have expanded in recent years, UV light therapy remains an essential therapeutic option for patients with psoriasis. Phototherapy is efficacious, is cost-effective, and generally lacks the systemic immunosuppressive properties of both traditional and biologic systemic therapies. Various spectra of UVB and UVA wavelengths have been used to treat psoriasis. Although it has been known for many centuries that some skin diseases improve with sun exposure, scientific investigation of phototherapeutic modalities did not begin until the late 19th century with the work of Niels Ryberg Finsen who received the Nobel Prize in 1903 for his work developing phototherapy for the treatment of cutaneous tuberculosis. Goeckerman4Goeckerman W. Treatment of psoriasis.Northwest Med. 1925; 24: 229-231Google Scholar first described the use of broadband (BB)-UVB in combination with day and night applications of crude coal tar for the successful treatment of psoriasis. This therapy was carried out while patients were admitted to the hospital for several weeks. During the years after the development of the Goeckerman4Goeckerman W. Treatment of psoriasis.Northwest Med. 1925; 24: 229-231Google Scholar regimen, several modifications and simplifications were made. In the 1950s, the Ingram5Ingram J.T. The significance and management of psoriasis.Br Med J. 1954; 2: 823-828Crossref PubMed Google Scholar regimen was developed, which replaced crude coal tar with anthralin. Subsequent studies have demonstrated that a lubricating base may be used instead of crude coal tar. However, a 1983 study demonstrated that suberythemogenic doses of UVB and coal tar were more efficacious than UVB and a lubricating base.6Lowe N.J. Wortzman M.S. Breeding J. Koudsi H. Taylor L. Coal tar phototherapy for psoriasis reevaluated: erythemogenic versus suberythemogenic ultraviolet with a tar extract in oil and crude coal tar.J Am Acad Dermatol. 1983; 8: 781-789Abstract Full Text PDF PubMed Scopus (0) Google Scholar, 7Lowe N.J. Contribution of topical tar oil to ultraviolet B phototherapy for psoriasis.J Am Acad Dermatol. 1986; 15: 1053-1055Abstract Full Text PDF PubMed Google Scholar Clear emollients such as mineral oil also enhance the efficacy of UVB by improving the optical properties of the skin; their use facilitated the shift of UVB as an outpatient, rather than an inpatient or day hospital, treatment modality.8Le Vine M.J. White H.A. Parrish J.A. Components of the Goeckerman regimen.J Invest Dermatol. 1979; 73: 170-173Abstract Full Text PDF PubMed Google Scholar, 9Berne B. Blom I. Spangberg S. Enhanced response of psoriasis to UVB therapy after pretreatment with a lubricating base: a single-blind controlled study.Acta Derm Venereol. 1990; 70: 474-477PubMed Google Scholar, 10LeVine M.J. Parrish J.A. Outpatient phototherapy of psoriasis.Arch Dermatol. 1980; 116: 552-554Crossref PubMed Google Scholar In the 1980s, a new type of UVB bulb with a narrow emission between 311 and 313 nm was developed and found to have superior efficacy to BB-UVB light11Walters I.B. Burack L.H. Coven T.R. Gilleaudeau P. Krueger J.G. Suberythemogenic narrow-band UVB is markedly more effective than conventional UVB in treatment of psoriasis vulgaris.J Am Acad Dermatol. 1999; 40: 893-900Abstract Full Text Full Text PDF PubMed Scopus (0) Google Scholar; this new UVB treatment is now commonly referred to as narrowband (NB)-UVB therapy. Because keratinocyte hyperproliferation is a hallmark feature of psoriasis, it was originally believed that the mechanism of action of UV light treatment in psoriasis was through a direct effect of UV light on DNA by inhibition of cellular turnover. With newer evidence firmly demonstrating that psoriasis is an immunologic disease, the role of the immunosuppressive effects of UV light in the treatment of psoriasis has been better appreciated. UV light (both UVB and UVA) is locally immunosuppressive by its direct effects on Langerhans cells and indirect effects on numerous cytokines and adhesion molecules, which can lead to a switch from a T-helper (Th) 1 to a Th 2 phenotype.12Lui H. Phototherapy of psoriasis: update with practical pearls.J Cutan Med Surg. 2002; 6: 17-21Crossref PubMed Google Scholar, 13Zanolli M. Phototherapy treatment of psoriasis today.J Am Acad Dermatol. 2003; 49: S78-S86Abstract Full Text Full Text PDF PubMed Google Scholar Other effects of UV light include inhibition of both epidermal hyperproliferation and angiogenesis. Furthermore, UV light causes a selective reduction in T lymphocytes within psoriatic skin via apoptosis. BB-UVB, NB-UVB, and psoralen plus UVA (PUVA) can all induce apoptosis of T lymphocytes,14Krueger J.G. Wolfe J.T. Nabeya R.T. Vallat V.P. Gilleaudeau P. Heftler N.S. et al.Successful ultraviolet B treatment of psoriasis is accompanied by a reversal of keratinocyte pathology and by selective depletion of intraepidermal T cells.J Exp Med. 1995; 182: 2057-2068Crossref PubMed Scopus (0) Google Scholar, 15Ozawa M. Ferenczi K. Kikuchi T. Cardinale I. Austin L.M. Coven T.R. et al.312-Nanometer ultraviolet B light (narrow-band UVB) induces apoptosis of T cells within psoriatic lesions.J Exp Med. 1999; 189: 711-718Crossref PubMed Scopus (249) Google Scholar, 16Johnson R. Staiano-Coico L. Austin L. Cardinale I. Nabeya-Tsukifuji R. Krueger J.G. PUVA treatment selectively induces a cell cycle block and subsequent apoptosis in human T-lymphocytes.Photochem Photobiol. 1996; 63: 566-571Crossref PubMed Google Scholar which may play an important role in the mechanism involved in remissions of psoriasis. Ancient Egyptians knew that natural photosensitizing compounds found in plants, combined with exposure to natural sunlight, were effective for the treatment of vitiligo. Trimethylpsoralen, a synthetic psoralen, was first used for the treatment of vitiligo and has since been used to successfully treat many other inflammatory photosensitive diseases such as cutaneous T-cell lymphoma, atopic dermatitis, and lichen planus.17Morison W.L. Psoralen ultraviolet A therapy in 2004.Photodermatol Photoimmunol Photomed. 2004; 20: 315-320Crossref PubMed Scopus (0) Google Scholar In the 1970s, oral ingestion of 8-methoxypsoralen combined with high-intensity UVA (known as PUVA photochemotherapy) was shown to be effective for the treatment of psoriasis18Parrish J.A. Fitzpatrick T.B. Tanenbaum L. Pathak M.A. Photochemotherapy of psoriasis with oral methoxsalen and longwave ultraviolet light.N Engl J Med. 1974; 291: 1207-1211Crossref PubMed Google Scholar; in 1982 PUVA was Food and Drug Administration (FDA) approved for psoriasis. All patients who are considered for treatment with phototherapy or photochemotherapy must have a complete history and physical examination. Patients with a known history of lupus erythematosus or xeroderma pigmentosum should not be treated with phototherapy or photochemotherapy. Patients with a history of a photosensitivity disorder, taking photosensitizing medications, with a history of melanoma, with atypical nevi, with multiple risk factors for melanoma, with multiple nonmelanoma skin cancers, or who are immunosuppressed as a result of organ transplantation should be screened carefully before initiating phototherapy or photochemotherapy. They should also be advised that adherence to their follow-up visits is imperative to obtaining maximal results. Office phototherapy and photochemotherapy should be performed under the direction of a dermatologist with the appropriate training and expertise in this area. Experts recommend that patients be examined approximately once a month or more often if necessary, although specific data on the frequency of evaluations during phototherapy or photochemotherapy are lacking. Each patient's treatment should be closely monitored by a nurse or phototherapy technician with proper training, and any abnormal findings should be transmitted to the treating dermatologist. All phototherapy equipment should be maintained and regularly calibrated by appropriately trained personnel. Accurate records of the dosage and number of treatments along with any side effects should be maintained for every patient. Traditional BB-UVB radiation has been used for the treatment of psoriasis for more than 75 years. In recent years phototherapy has maintained its important role in the treatment of psoriasis, either as monotherapy or in combination with topical or systemic agents. In a study published in 1975, it was shown that 313 nm was the most effective wavelength in clearing psoriasis.19Alsins J. Claesson S. Fischer T. Juhlin L. Development of high intensity narrow-band lamps and studies of the irradiation effect on human skin: irradiation with high intensity lamps.Acta Derm Venereol. 1975; 55: 261-271PubMed Google Scholar Further study using monochromatic UV radiation ranging from 254 to 313 nm revealed that suberythemogenic exposure to 313-nm light led to significant improvement of psoriasis.20Parrish J.A. Jaenicke K.F. Action spectrum for phototherapy of psoriasis.J Invest Dermatol. 1981; 76: 359-362Abstract Full Text PDF PubMed Google Scholar UVB interferes with the synthesis of proteins and nucleic acids, which leads to a decreased proliferation of epidermal keratinocytes. Early changes after exposure to UV radiation include formation of pyrimidine dimers, membrane lipid peroxidation, and induction of transcriptional factors. Delayed changes include alteration of antigen-presenting cells and cellular signaling mechanisms.13Zanolli M. Phototherapy treatment of psoriasis today.J Am Acad Dermatol. 2003; 49: S78-S86Abstract Full Text Full Text PDF PubMed Google Scholar UVB decreases the number of Langerhans cells21Duthie M.S. Kimber I. Norval M. The effects of ultraviolet radiation on the human immune system.Br J Dermatol. 1999; 140: 995-1009Crossref PubMed Scopus (187) Google Scholar thus inhibiting the ability of dendritic cells to present antigens, secondary to membrane damage and reduction in the expression of cell surface molecules while altering the secretion of cytokines in the macrophages.22Sethi G. Sodhi A. Role of p38 mitogen-activated protein kinase and caspases in UV-B-induced apoptosis of murine peritoneal macrophages.Photochem Photobiol. 2004; 79: 48-54PubMed Google Scholar The newly discovered subset of T cells, Th17 cells, are now considered to play a central role in the immunopathogenesis of psoriasis and are likewise down-regulated by UVB.23Nickoloff B.J. Cracking the cytokine code in psoriasis.Nat Med. 2007; 13: 242-244Crossref PubMed Scopus (140) Google Scholar Early studies demonstrated the efficacy of BB-UVB monotherapy in psoriasis. One study reported resolution of psoriasis in 20 of 28 patients treated with erythemogenic doses of home-based UVB therapy24Larko O. Swanbeck G. Home solarium treatment of psoriasis.Br J Dermatol. 1979; 101: 13-16Crossref PubMed Google Scholar whereas another study demonstrated efficacy in 18 of 20 patients treated with 3 times weekly outpatient UVB phototherapy with concomitant white petrolatum.25Adrian R.M. Parrish J.A. Momtaz T.K. Karlin M.J. Outpatient phototherapy for psoriasis.Arch Dermatol. 1981; 117: 623-626Crossref PubMed Google Scholar Similar observations were made by Levine and Parrish10LeVine M.J. Parrish J.A. Outpatient phototherapy of psoriasis.Arch Dermatol. 1980; 116: 552-554Crossref PubMed Google Scholar when white petrolatum was combined with UV. Remission times were prolonged using maintenance therapy.26Boer J. Schothorst A.A. Suurmond D. UV-B phototherapy of psoriasis.Dermatologica. 1980; 161: 250-258Crossref PubMed Google Scholar, 27Stern R.S. Armstrong R.B. Anderson T.F. Bickers D.R. Lowe N.J. Harber L. et al.Effect of continued ultraviolet B phototherapy on the duration of remission of psoriasis: a randomized study.J Am Acad Dermatol. 1986; 15: 546-552Abstract Full Text PDF PubMed Google Scholar, 28Boztepe G. Karaduman A. Sahin S. Hayran M. Kolemen F. The effect of maintenance narrow-band ultraviolet B therapy on the duration of remission for psoriasis: a prospective randomized clinical trial.Int J Dermatol. 2006; 45: 245-250Crossref PubMed Scopus (0) Google Scholar The advent of NB-UVB lamps improved the use of UVB therapy in psoriasis and is widely considered to be preferable to BB-UVB therapy. NB-UVB use was initially popularized in the United Kingdom and Europe in the mid-1980s, and became available in the United States approximately one decade later. Many of the studies evaluating NB-UVB were right-left half body comparisons of NB-UVB with BB-UVB.11Walters I.B. Burack L.H. Coven T.R. Gilleaudeau P. Krueger J.G. Suberythemogenic narrow-band UVB is markedly more effective than conventional UVB in treatment of psoriasis vulgaris.J Am Acad Dermatol. 1999; 40: 893-900Abstract Full Text Full Text PDF PubMed Scopus (0) Google Scholar, 29Karvonen J. Kokkonen E.L. Ruotsalainen E. 311 nm UVB lamps in the treatment of psoriasis with the Ingram regimen.Acta Derm Venereol. 1989; 69: 82-85PubMed Google Scholar, 30Larko O. Treatment of psoriasis with a new UVB-lamp.Acta Derm Venereol. 1989; 69: 357-359PubMed Google Scholar, 31Coven T.R. Burack L.H. Gilleaudeau R. Keogh M. Ozawa M. Krueger J.G. Narrowband UV-B produces superior clinical and histopathological resolution of moderate-to-severe psoriasis in patients compared with broadband UV-B.Arch Dermatol. 1997; 133: 1514-1522Crossref PubMed Google Scholar One such study demonstrated that although 60% of patients had the same efficacy regardless of which type of UVB was used, 40% of patients treated with NB-UVB had superior results.29Karvonen J. Kokkonen E.L. Ruotsalainen E. 311 nm UVB lamps in the treatment of psoriasis with the Ingram regimen.Acta Derm Venereol. 1989; 69: 82-85PubMed Google Scholar Other similar studies have demonstrated more rapid clearing in patients treated with NB-UVB compared with those treated with BB-UVB11Walters I.B. Burack L.H. Coven T.R. Gilleaudeau P. Krueger J.G. Suberythemogenic narrow-band UVB is markedly more effective than conventional UVB in treatment of psoriasis vulgaris.J Am Acad Dermatol. 1999; 40: 893-900Abstract Full Text Full Text PDF PubMed Scopus (0) Google Scholar, 30Larko O. Treatment of psoriasis with a new UVB-lamp.Acta Derm Venereol. 1989; 69: 357-359PubMed Google Scholar and treatment with NB-UVB was more likely than BB-UVB to lead to histopathological resolution of psoriasis lesions (88% compared with 59%).31Coven T.R. Burack L.H. Gilleaudeau R. Keogh M. Ozawa M. Krueger J.G. Narrowband UV-B produces superior clinical and histopathological resolution of moderate-to-severe psoriasis in patients compared with broadband UV-B.Arch Dermatol. 1997; 133: 1514-1522Crossref PubMed Google Scholar The potential value of maintenance therapy with NB-UVB has also been evaluated. After 12 weeks of NB-UVB therapy, 55% of patients who received NB-UVB twice weekly for 4 weeks followed by once weekly for 4 weeks were in remission at 1 year compared with 33% of patients who did not receive maintenance therapy.24Larko O. Swanbeck G. Home solarium treatment of psoriasis.Br J Dermatol. 1979; 101: 13-16Crossref PubMed Google Scholar A standard protocol is recommended for the use of phototherapy in the management of psoriasis. Basic phototherapy education should be given to all patients. This must include education about the use of goggles in all patients and the use of genital shields in male patients. The dosage of UVB may be administered according to the Fitzpatrick skin type32Wolff K. Gschnait F. Honigsmann H. Konrad K. Parrish J.A. Fitzpatrick T.B. Phototesting and dosimetry for photochemotherapy.Br J Dermatol. 1977; 96: 1-10Crossref PubMed Google Scholar or the minimal erythema dose (MED), with subsequent dosages adjusted accordingly. (Please see Table I, Table II for examples of well-accepted, published guidelines for dosing of both BB-UVB and NB-UVB.)Table IDosing guidelines for broadband ultraviolet BAccording to skin type:Skin typeInitial UVB dose, mJ/cm2UVB increase after each treatment, mJ/cm2I205II2510III3015IV4020V5025VI6030According to MED:Initial UVB50% of MEDTreatments 1-10Increase by 25% of initial MEDTreatments 11-20Increase by 10% of initial MEDTreatments ≥21As ordered by physicianIf subsequent treatments are missed for:4-7 dKeep dose same1-2 wkDecrease dose by 50%2-3 wkDecrease dose by 75%3-4 wkStart overMED, Minimal erythema dose; UV, ultraviolet.Administered 3-5×/wk.Adapted with permission from Zanolli et al.169Zanolli M.D. Feldman S.R. Phototherapy treatment protocols for psoriasis and other phototherapy responsive dermatoses. 2nd ed. Informa Healthcare, New York2004Crossref Google Scholar Open table in a new tab Table IIDosing guidelines for narrowband ultraviolet BAccording to skin type:Skin typeInitial UVB dose, mJ/cm2UVB increase after each treatment, mJ/cm2Maximum dose, mJ/cm2I130152000II220252000III260403000IV330453000V350605000VI400655000According to MED:Initial UVB50% of MEDTreatments 1-20Increase by 10% of initial MEDTreatments ≥21Increase as ordered by physicianIf subsequent treatments are missed for:4-7 dKeep dose same1-2 wkDecrease dose by 25%2-3 wkDecrease dose by 50% or start over3-4 wkStart overMaintenance therapy for NB-UVB after >95% clearance:1×/wkNB-UVB for 4 wkKeep dose same1×/2 wkNB-UVB for 4 wkDecrease dose by 25%1×/4 wkNB-UVB50% of Highest doseMED, Minimal erythema dose; NB, narrowband; UV, ultraviolet.Administered 3-5×/wk.Because there is broad range of MED for NB-UVB by skin type, MED testing is generally recommended.It is critically important to meter UVB machine once weekly. UVB lamps steadily lose power. If UV output is not periodically measured and actual output calibrated into machine, clinician may have false impression that patient can be treated with higher doses when machine is actually delivering much lower dose than number entered.Minimum frequency of phototherapy sessions required per week for successful maintenance as well as length of maintenance period varies tremendously between individuals. Above table represents most ideal situation where patient can taper off phototherapy. In reality, many patients require 1×/wk NB-UVB phototherapy indefinitely for successful long-term maintenance.Adapted with permission from Do and Koo.170Do A. Koo J. Initiating narrow-band UVB for the treatment of psoriasis: how to do MED skin testing.Psoriasis Forum. 2004; 10: 7-11Crossref Google Scholar Open table in a new tab MED, Minimal erythema dose; UV, ultraviolet. Administered 3-5×/wk. Adapted with permission from Zanolli et al.169Zanolli M.D. Feldman S.R. Phototherapy treatment protocols for psoriasis and other phototherapy responsive dermatoses. 2nd ed. Informa Healthcare, New York2004Crossref Google Scholar MED, Minimal erythema dose; NB, narrowband; UV, ultraviolet. Administered 3-5×/wk. Because there is broad range of MED for NB-UVB by skin type, MED testing is generally recommended. It is critically important to meter UVB machine once weekly. UVB lamps steadily lose power. If UV output is not periodically measured and actual output calibrated into machine, clinician may have false impression that patient can be treated with higher doses when machine is actually delivering much lower dose than number entered. Minimum frequency of phototherapy sessions required per week for successful maintenance as well as length of maintenance period varies tremendously between individuals. Above table represents most ideal situation where patient can taper off phototherapy. In reality, many patients require 1×/wk NB-UVB phototherapy indefinitely for successful long-term maintenance. Adapted with permission from Do and Koo.170Do A. Koo J. Initiating narrow-band UVB for the treatment of psoriasis: how to do MED skin testing.Psoriasis Forum. 2004; 10: 7-11Crossref Google Scholar Acute side effects with BB-UVB therapy include erythema, itching, burning, and stinging. The use of eye protection with goggles is required to decrease the risk of UVB-related cataract formation. Reactivation of herpes simplex virus infection may occur after UVB treatment. Photoaging is a long-term side effect, and features of dermatoheliosis including wrinkling, lentigines, and telangiectasias may occur. Photocarcinogenesis is a potential adverse effect of UVB phototherapy; however, numerous studies have failed to show such an effect in patients with psoriasis after UVB therapy.33Stern R.S. Laird N. The carcinogenic risk of treatments for severe psoriasis: photochemotherapy follow-up study.Cancer. 1994; 73: 2759-2764Crossref PubMed Scopus (0) Google Scholar, 34Lee E. Koo J. Berger T. UVB phototherapy and skin cancer risk: a review of the literature.Int J Dermatol. 2005; 44: 355-360Crossref PubMed Scopus (141) Google Scholar Long-term exposure to BB-UVB (>300 treatments) may be associated with an increased risk of genital tumors in men treated without genital shielding; the routine use of shields has been recommended to avoid such an effect.35Studniberg H.M. Weller P. PUVA, UVB, psoriasis, and nonmelanoma skin cancer.J Am Acad Dermatol. 1993; 29: 1013-1022Abstract Full Text PDF PubMed Google Scholar In addition to genital shielding, standard practice involves covering the face as long as there are no lesions of psoriasis on the face or, if there are, minimizing the dose to the face as lesions on the face tend to respond to lower doses of UVB compared with lesions on trunk or extremities. Burning with NB-UVB is generally comparable with that observed with BB-UVB exposure. Although NB-UVB is reported to be less phototoxic than BB-UVB in some studies,36Storbeck K. Holzle E. Schurer N. Lehmann P. Plewig G. Narrow-band U.V.B. (311 nm) versus conventional broad-band UVB with and without dithranol in phototherapy for psoriasis.J Am Acad Dermatol. 1993; 28: 227-231Abstract Full Text PDF PubMed Google Scholar, 37Picot E. Meunier L. Picot-Debeze M.C. Peyron J.L. Meynadier J. Treatment of psoriasis with a 311-nm UVB lamp.Br J Dermatol. 1992; 127: 509-512Crossref PubMed Scopus (114) Google Scholar other studies failed to show this discrepancy.31Coven T.R. Burack L.H. Gilleaudeau R. Keogh M. Ozawa M. Krueger J.G. Narrowband UV-B produces superior clinical and histopathological resolution of moderate-to-severe psoriasis in patients compared with broadband UV-B.Arch Dermatol. 1997; 133: 1514-1522Crossref PubMed Google Scholar, 38Alora M.B. Taylor C.R. Narrow-band (311 nm) UVB phototherapy: an audit of the first year's experience at the Massachusetts General Hospital.Photodermatol Photoimmunol Photomed. 1997; 13: 82-84Crossref PubMed Google Scholar Although an unusual occurrence, lesional blistering has also been reported after exposure to NB-UVB.39George S.A. Ferguson J. Lesional blistering following narrow-band (TL-01) UVB phototherapy for psoriasis: a report of four cases.Br J Dermatol. 1992; 127: 445-446Crossref PubMed Scopus (0) Google Scholar Murine models of photocarcinogenesis suggest that NB-UVB may be 2 to 3 times more carcinogenic per MED as compared with BB-UVB.40Flindt-Hansen H. McFadden N. Eeg-Larsen T. Thune P. Effect of a new narrow-band UVB lamp on photocarcinogenesis in mice.Acta Derm Venereol. 1991; 71: 245-248PubMed Google Scholar, 41Gibbs N.K. Traynor N.J. MacKie R.M. Campbell I. Johnson B.E. Ferguson J. The phototumorigenic potential of broad-band (270-350 nm) and narrow-band (311-313 nm) phototherapy sources cannot be predicted by their edematogenic potential in hairless mouse skin.J Invest Dermatol. 1995; 104: 359-363Abstract Full Text PDF PubMed Google Scholar However, because of the higher efficacy of NB-UVB

Objective To develop an evidence‐based guideline for the pharmacologic and nonpharmacologic treatment of psoriatic arthritis (PsA), as a collaboration between the American College of Rheumatology (ACR) and the National Psoriasis Foundation (NPF). Methods We identified critical outcomes in PsA and clinically relevant PICO (population/intervention/comparator/outcomes) questions. A Literature Review Team performed a systematic literature review to summarize evidence supporting the benefits and harms of available pharmacologic and nonpharmacologic therapies for PsA. GRADE (Grading of Recommendations Assessment, Development and Evaluation) methodology was used to rate the quality of the evidence. A voting panel, including rheumatologists, dermatologists, other health professionals, and patients, achieved consensus on the direction and the strength of the recommendations. Results The guideline covers the management of active PsA in patients who are treatment‐naive and those who continue to have active PsA despite treatment, and addresses the use of oral small molecules, tumor necrosis factor inhibitors, interleukin‐12/23 inhibitors (IL‐12/23i), IL‐17 inhibitors, CTLA4‐Ig (abatacept), and a JAK inhibitor (tofacitinib). We also developed recommendations for psoriatic spondylitis, predominant enthesitis, and treatment in the presence of concomitant inflammatory bowel disease, diabetes, or serious infections. We formulated recommendations for a treat‐to‐target strategy, vaccinations, and nonpharmacologic therapies. Six percent of the recommendations were strong and 94% conditional, indicating the importance of active discussion between the health care provider and the patient to choose the optimal treatment. Conclusion The 2018 ACR/NPF PsA guideline serves as a tool for health care providers and patients in the selection of appropriate therapy in common clinical scenarios. Best treatment decisions consider each individual patient situation. The guideline is not meant to be proscriptive and should not be used to limit treatment options for patients with PsA.

To evaluate the safety and efficacy of long-term treatment of psoriasis with etanercept, 50 mg twice weekly.A phase 3, randomized, double-blind trial with an open-label extension. A total of 618 adult patients with moderate to severe plaque psoriasis were studied at 39 medical centers in the United States and Canada from May 23, 2003, through June 22, 2005.Patients were randomized to receive placebo or etanercept for 12 weeks. Beginning with week 13, all patients (N=591) received etanercept.Exposure-adjusted adverse event rates were calculated. Efficacy measures included efficacy and patient global assessment of psoriasis.Exposure-adjusted rates of adverse events, serious adverse events, infections, and serious infections were similar for placebo and etanercept treatments. Nonneutralizing antibodies to etanercept, observed in 18.3% of patients, had no apparent effect on safety or efficacy. Patients responded within 2 weeks to etanercept, with statistically significant differences in the Psoriasis Area and Severity Index and Dermatology Life Quality Index between the etanercept and placebo groups at week 12. At week 24, after 12 weeks of open-label etanercept treatment, patients in the original placebo group had clinical benefits comparable to those of patients in the original etanercept group. As both groups progressed through the open-label period, the Psoriasis Area and Severity Index response peaked at week 48. At week 96, 51.6% of the original placebo-treated patients and 51.1% of the original etanercept-treated patients had improvements from baseline in the Psoriasis Area and Severity Index of at least 75%.Extended exposure to 50 mg of etanercept twice weekly resulted in exposure-adjusted rates of adverse events and infections similar to those in patients receiving placebo. Improvements in physician- and patient-reported measures of psoriasis severity were observed for up to 96 weeks of continuous etanercept therapy. Trial Registration clinicaltrials.gov Identifier NCT00111449.

Psoriasis is a chronic, inflammatory, multisystem disease that affects up to 3.2% of the US population. This guideline addresses important clinical questions that arise in psoriasis management and care, providing recommendations on the basis of available evidence.

AbstractBackground: There are reports of rare adverse effects of tumor necrosis factor (TNF) inhibitors, including infections, malignancies, and induction of autoimmune conditions. Intriguing, are cases of induction or exacerbation of psoriasis in conjunction with TNF inhibitor therapy, given that they are approved for treatment of the same condition. Objective: Published cases of psoriasis occurring during anti-TNF therapy were analyzed, including overviews of proposed etiologies and treatment recommendations. Methods: A literature search using Ovid MEDLINE and PubMed was performed for articles published between January 1990 and September 2007 to collect reported cases of psoriasis in patients receiving therapy with TNF blocking agents. Results: A total of 127 cases were identified: 70 in patients on infliximab (55.1%), 35 with etanercept (27.6%), and 22 with adalimumab (17.3%). Females comprised 58% of cases; mean age of reported patients was 45.8 years, and the time from initiation of treatment to onset of lesions averaged 10.5 months. These patients suffered from a number of primary conditions, with rheumatoid arthritis, ankylosing spondylitis, and Crohn's disease accounting for the vast majority. Palmoplantar pustular psoriasis was observed in 40.5% of the cases, with plaque-type psoriasis in 33.1%, and other types comprising the remainder. Topical corticosteroids were the most commonly employed treatment modality but led to resolution in only 26.8% of cases in which they were employed solely. Switching to a different anti-TNF agent led to resolution in 15.4% of cases. Cessation of anti-TNF therapy with systemic therapy led to resolution in 64.3% of cases. Conclusion: More information and cases are needed. Biopsies of TNF-blockade-induced lesions may reveal what cytokines and cell types drive the development of these lesions. Additionally, there is a need to develop an algorithm to treat this paradoxical side effect of therapy with TNF-blockers.KeywordsBlockadeexacerbationpsoriasistherapyTNF

Journal Article Secukinumab administration by pre‐filled syringe: efficacy, safety and usability results from a randomized controlled trial in psoriasis (FEATURE) Get access A. Blauvelt, A. Blauvelt Oregon Medical Research Center 9495 SW Locust Street, Suite G Portland OR 97223 U.S.A Correspondence Andrew Blauvelt. E‐mail: ablauvelt@oregonmedicalresearch.com Search for other works by this author on: Oxford Academic Google Scholar J.C. Prinz, J.C. Prinz Department of Dermatology and Allergology Ludwig‐Maximilians‐University Munich Germany Search for other works by this author on: Oxford Academic Google Scholar A.B. Gottlieb, A.B. Gottlieb Tufts Medical Center Boston MA U.S.A Search for other works by this author on: Oxford Academic Google Scholar K. Kingo, K. Kingo Department of Dermatology and Venereology University of Tartu Tartu Estonia Search for other works by this author on: Oxford Academic Google Scholar H. Sofen, H. Sofen Department of Medicine/Dermatology UCLA School of Medicine Los Angeles CA U.S.A Search for other works by this author on: Oxford Academic Google Scholar M. Ruer‐Mulard, M. Ruer‐Mulard Le Bâteau Blanc‐Imm. A Centre Médical Martigues Bouches‐du‐Rhône France Search for other works by this author on: Oxford Academic Google Scholar V. Singh, V. Singh Novartis Healthcare Private Limited Hyderabad India Search for other works by this author on: Oxford Academic Google Scholar R. Pathan, R. Pathan Novartis Healthcare Private Limited Hyderabad India Search for other works by this author on: Oxford Academic Google Scholar C. Papavassilis, C. Papavassilis Novartis Pharma AG Basel Switzerland Search for other works by this author on: Oxford Academic Google Scholar S. Cooper, S. Cooper Novartis Pharmaceuticals Corporation East Hanover NJ U.S.A Search for other works by this author on: Oxford Academic Google Scholar ... Show more for the FEATURE Study Group for the FEATURE Study Group Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 172, Issue 2, 1 February 2015, Pages 484–493, https://doi.org/10.1111/bjd.13348 Published: 01 February 2015

Tofacitinib is an oral Janus kinase inhibitor being investigated for psoriasis.To determine the 16-week efficacy and safety of two oral tofacitinib doses vs. placebo in patients with moderate-to-severe chronic plaque psoriasis.Patients in two similarly designed phase III studies (OPT Pivotal 1, NCT01276639, n = 901; OPT Pivotal 2, NCT01309737, n = 960) were initially randomized 2 : 2 : 1 to tofacitinib 10 or 5 mg or placebo, twice daily. Coprimary efficacy end points (week 16) included the proportion of patients achieving Physician's Global Assessment (PGA) of 'clear' or 'almost clear' (PGA response) and the proportion achieving ≥ 75% reduction in Psoriasis Area and Severity Index (PASI 75).Across OPT Pivotal 1 and OPT Pivotal 2, 745 patients received tofacitinib 5 mg, 741 received tofacitinib 10 mg and 373 received placebo. At week 16, a greater proportion of patients achieved PGA responses with tofacitinib 5 and 10 mg twice daily vs. placebo (OPT Pivotal 1, 41·9% and 59·2% vs. 9·0%; OPT Pivotal 2, 46·0% and 59·1% vs. 10·9%; all P < 0·001). Higher PASI 75 rates were observed with tofacitinib vs. placebo (OPT Pivotal 1, 39·9%, 59·2% and 6·2%, respectively, for tofacitinib 5 and 10 mg twice daily and placebo; OPT Pivotal 2, 46·0%, 59·6% and 11·4%; all P < 0·001 vs. placebo). Adverse event (AE) rates appeared generally similar across groups; rates of serious AEs, infections, malignancies and discontinuations due to AEs were low. Twelve patients reported herpes zoster across the tofacitinib treatment groups in both studies vs. none in the respective placebo groups. The most common AE across groups was nasopharyngitis.Oral tofacitinib demonstrated significant efficacy vs. placebo during the initial 16 weeks of treatment in patients with moderate-to-severe psoriasis. Safety findings were consistent with prior studies.

Nuclear factor kappa B (NF-κB) is a protein transcription factor that orchestrates inflammation and other complex biological processes. It is a key regulatory element in a variety of immune and inflammatory pathways, in cellular proliferation and differentiation and in apoptosis. Therefore NF-κB is a crucial mediator involved in the pathogenesis of psoriasis. Psoriasis, an inflammatory dermatosis, is marked by elevated levels of active, phosphorylated NF-κB. Genomic studies have also linked psoriasis with mediators in the NF-κB pathway. NF-κB has been hypothesized to connect the altered keratinocyte and immune cell behavior that characterizes the psoriatic milieu. Several anti-psoriatic therapies, including tumor necrosis factor-α blockers and glucocorticoids, reduce active NF-κB levels and related down-stream elements, and other biologics currently in development, including interleukin-17 blockers, may also target this pathway. Compounds that specifically target NF-κB signaling may be developed as novel therapeutics for chronic inflammatory disorders including psoriasis. However, chronic NF-κB inhibition could also result in immunodeficiencies. Therefore, a delicate balance must be found that maximizes therapeutic potential while limiting harmful effects, and may be achieved through several possible approaches, including localized therapy, selective inhibition of NF-κB signaling in pathologic cells, incomplete pathway inhibition or short treatment durations.

<h3>Objective</h3> Evaluate ustekinumab, an anti-interleukin (IL)-12 and IL-23 antibody, effects on radiographic progression in psoriatic arthritis (PsA). <h3>Methods</h3> We conducted preplanned integrated analyses of combined radiographic data from PSUMMIT-1 and PSUMMIT-2 phase 3, randomised, controlled trials. Patients had active PsA despite prior conventional and/or biologic disease-modifying antirheumatic drugs (≥5/66 swollen, ≥5/68 tender joints, C-reactive protein ≥3.0 mg/L, documented plaque psoriasis). Patients (PSUMMIT-1, n=615; PSUMMIT-2, n=312) were randomised to ustekinumab 45 mg, 90 mg, or placebo, at weeks (wk) 0, 4 and every (q) 12 wks. At wk 16, patients with &lt;5% improvement in tender/swollen joint counts entered blinded early escape. All other placebo patients received ustekinumab 45 mg at wk 24 and wk 28, then q 12 wks. Radiographs of hands/feet at wks 0/24/52 were assessed using PsA-modified van der Heijde-Sharp (vdH-S) scores; combined PSUMMIT-1 and PSUMMIT-2 changes in total vdH-S scores from wk 0 to wk 24 comprised the prespecified primary radiographic analysis. Treatment effects were assessed using analysis of variance on van der Waerden normal scores (factors=treatment, baseline methotrexate usage, and study). <h3>Results</h3> Integrated data analysis results indicated that ustekinumab-treated patients (regardless of dose) demonstrated significantly less radiographic progression at wk 24 than did placebo recipients (wk 0–24 total vdH-S score mean changes: 0.4-combined/individual ustekinumab dose groups, 1.0-placebo; all p&lt;0.02). From wk 24 to wk 52, inhibition of radiographic progression was maintained for ustekinumab-treated patients, and progression was substantially reduced among initial placebo recipients who started ustekinumab at wk 16 or wk 24 (wk 24 – wk 52, total vdH-S score mean change: 0.08). <h3>Conclusions</h3> Ustekinumab 45 and 90 mg treatments significantly inhibited radiographic progression of joint damage in patients with active PsA.

Tildrakizumab is a high-affinity, humanized, IgG1/κ, anti-interleukin (IL)-23p19 monoclonal antibody that does not bind human IL-12 or p40 is being developed for the treatment of chronic plaque psoriasis.To evaluate the safety and efficacy of subcutaneous tildrakizumab in patients with moderate-to-severe chronic plaque psoriasis.A three-part, randomized, double-blind, phase IIb trial was conducted in 355 adults with chronic plaque psoriasis. Participants were randomized to receive subcutaneous tildrakizumab (5, 25, 100, 200 mg) or placebo at weeks 0 and 4 (part I) and every 12 weeks thereafter until week 52 (part II). Study drug was discontinued at week 52 and participants were followed through week 72 (part III). Primary efficacy end point was Psoriasis Area and Severity Index (PASI) 75 response at week 16. Adverse events (AEs) and vital signs were monitored throughout the study.At week 16, PASI 75 responses were 33·3% (n = 14), 64·4% (n = 58), 66·3% (n = 59), 74·4% (n = 64) and 4·4% (n = 2) in the 5-, 25-, 100- and 200-mg tildrakizumab and placebo groups, respectively (P ≤ 0·001 for each tildrakizumab dose vs. placebo). PASI 75 response was generally maintained through week 52; only eight of 222 participants who achieved PASI 75 response at week 52 and continued to part III relapsed following discontinuation up to week 72. Possible drug-related serious AEs included bacterial arthritis and lymphoedema (part I), and melanoma, stroke, epiglottitis and knee infection (part II).Tildrakizumab had treatment effects that were superior to placebo, maintained for 52 weeks of treatment, and persisted for 20 weeks after cessation. Tildrakizumab was generally safe and well tolerated. These results suggest that IL-23p19 is a key target for suppressing psoriasis.

Hidradenitis suppurativa is a severe and debilitating dermatologic disease. Clinical management is challenging and consists of both medical and surgical approaches, which must often be combined for best outcomes. Therapeutic approaches have evolved rapidly in the last decade and include the use of topical therapies, systemic antibiotics, hormonal therapies, and a wide range of immunomodulating medications. An evidence-based guideline is presented to support health care practitioners as they select optimal medical management strategies and is reviewed in this second part of the management guidelines. A therapeutic algorithm informed by the evidence available at the time of the review is provided.

<h2>Summary</h2><h3>Background</h3> The interleukin-23 (IL-23)/T-helper 17 cell pathway is implicated in psoriatic arthritis pathogenesis. Guselkumab, an IL-23 inhibitor that specifically binds the IL-23 p19 subunit, significantly and safely improved psoriatic arthritis in a phase 2 study. DISCOVER-2 was a phase 3 trial to assess guselkumab in biologic-naive patients with psoriatic arthritis. <h3>Methods</h3> This phase 3, double-blind, placebo-controlled study was done at 118 sites in 13 countries across Asia, Europe, and North America. We enrolled biologic-naive patients with active psoriatic arthritis (at least five swollen joints, at least five tender joints, and C-reactive protein ≥0·6 mg/dL) despite standard therapies. Patients were randomly assigned (1:1:1, computer-generated permuted blocks; stratified by baseline disease-modifying antirheumatic drug use and C-reactive protein concentration) to subcutaneous injections of guselkumab 100 mg every 4 weeks; guselkumab 100 mg at weeks 0, 4, then every 8 weeks; or placebo. The primary endpoint was American College of Rheumatology 20% improvement (ACR20) response at week 24 in all patients per assigned treatment group. Safety was assessed in all patients per treatment received. This trial is registered at ClinicalTrials.gov, NCT03158285 (active, not recruiting). <h3>Findings</h3> From July 13, 2017, to Aug 3, 2018, 1153 patients were screened, of whom 741 were randomly assigned to receive guselkumab every 4 weeks (n=246), every 8 weeks (n=248), or placebo (n=247). One patient in the every 4 weeks group and one in the placebo group did not start treatment, and the remaining 739 patients started treatment; 716 patients continued treatment up to week 24. Significantly greater proportions of patients in the guselkumab every 4 weeks group (156 [64%] of 245 [95% CI 57–70]) and every 8 weeks group (159 [64%] of 248 [58–70]) than in the placebo group (81 [33%] of 246 [27–39]) achieved an ACR20 response at week 24 (percentage differences <i>vs</i> placebo 31% [95% CI 22–39] for the every 4 weeks group and 31% [23–40] for the every 8 weeks group; both p<0·0001). Up to week 24, serious adverse events occurred in eight (3%) of 245 patients receiving guselkumab every 4 weeks (three serious infections), three (1%) of 248 receiving guselkumab every 8 weeks (one serious infection), and seven (3%) of 246 receiving placebo (one serious infection). No deaths occurred. <h3>Interpretation</h3> Guselkumab, a human monoclonal antibody that specifically inhibits IL-23 by binding the cytokine's p19 subunit, was efficacious and demonstrated an acceptable benefit–risk profile in patients with active psoriatic arthritis who were naive to treatment with biologics. These data support the use of selective inhibition of IL-23 to treat psoriatic arthritis. <h3>Funding</h3> Janssen Research and Development.

Psoriasis is a chronic inflammatory disease involving multiple organ systems and affecting approximately 2% of the world's population. In this guideline, we focus the discussion on systemic, nonbiologic medications for the treatment of this disease. We provide detailed discussion of efficacy and safety for the most commonly used medications, including methotrexate, cyclosporine, and acitretin, and provide recommendations to assist prescribers in initiating and managing patients on these treatments. Additionally, we discuss newer therapies, including tofacitinib and apremilast, and briefly touch on a number of other medications, including fumaric acid esters (used outside the United States) and therapies that are no longer widely used for the treatment of psoriasis (ie, hydroxyurea, leflunomide, mycophenolate mofetil, thioguanine, and tacrolimus). Psoriasis is a chronic inflammatory disease involving multiple organ systems and affecting approximately 2% of the world's population. In this guideline, we focus the discussion on systemic, nonbiologic medications for the treatment of this disease. We provide detailed discussion of efficacy and safety for the most commonly used medications, including methotrexate, cyclosporine, and acitretin, and provide recommendations to assist prescribers in initiating and managing patients on these treatments. Additionally, we discuss newer therapies, including tofacitinib and apremilast, and briefly touch on a number of other medications, including fumaric acid esters (used outside the United States) and therapies that are no longer widely used for the treatment of psoriasis (ie, hydroxyurea, leflunomide, mycophenolate mofetil, thioguanine, and tacrolimus). The American Academy of Dermatology (AAD) strives to produce clinical guidelines that reflect the best available evidence supplemented with the judgment of expert clinicians. Significant efforts are taken to minimize the potential for conflicts of interest to influence guideline content. The management of conflict of interest for this guideline complies with the Council of Medical Specialty Societies’ “Code of Interactions with Companies.” Funding of guideline production by medical or pharmaceutical entities is prohibited, full disclosure is obtained and evaluated for all guideline contributors throughout the guideline development process, and recusal is used to manage identified relationships. The AAD conflict of interest policy summary may be viewed at www.aad.org. The information below represents the author's disclosed relationship with industry during guideline development. Authors (listed alphabetically) with relevant conflicts with respect to this guideline are noted with an asterisk (∗). In accordance with AAD policy, a minimum 51% of workgroup members did not have any relevant conflicts of interest. Participation in one or more of the below-listed activities constitutes a relevant conflict:•Service as a member of a speaker bureau, consultant, advisory board, for pharmaceutical companies on psoriasis disease state or psoriasis drugs in development or United States Food and Drug Administration (FDA) approved•Sponsored research funding or investigator-initiated studies with partial/full funding from pharmaceutical companies on psoriasis disease state or psoriasis drugs in development or FDA approved If a potential conflict was noted, the work group member recused themselves from discussion and drafting of recommendations pertinent to the topic area of interest. Complete group consensus was obtained for draft recommendations. Areas where complete consensus was not achieved are shown transparently in the guideline. Adherence to this guideline will not ensure successful treatment in every situation. Furthermore, these guidelines should not be interpreted as setting a standard of care, nor should they be deemed either inclusive of all proper methods of care, or exclusive of other methods of care reasonably directed toward obtaining the same results. The ultimate judgment regarding the propriety of any specific therapy must be made by the physician and the patient in light of circumstances presented by the individual patient and the known variability and biologic behavior of the disease. Furthermore, the treatment dosages used in clinical trials may not be effective in certain cases, and some patients may require shorter intervals between doses and/or higher treatment doses of a particular treatment methodology. This guideline reflects the best available data at the time the guideline was prepared. The results of future studies may require revisions to the recommendations in this guideline to reflect new data. This guideline will cover the use of oral-systemic, nonbiologic medication in the treatment of psoriasis. For a full description of the methodology used herein, please refer to Appendix 1. See section below for full definition statement (Table I).Table IClinical questionsWhat are the efficacy, effectiveness, adverse effects, contraindications, and recommended monitoring for oral systemic therapies used to treat psoriasis in adults?1.Methotrexate—FDA approval 19722.Apremilast—FDA approval 20143.Cyclosporine—FDA approval 19974.Acitretin—FDA approval 19975.Tofacitinib—Not FDA approved for psoriasis6.Fumaric acid esters—Not FDA approved for psoriasis7.Hydroxyurea—Not FDA approved for psoriasis8.Mycophenolate mofetil—Not FDA approved for psoriasis9.Azathioprine— Not FDA approved for psoriasis10.Leflunomide—Not FDA approved for psoriasis11.Tacrolimus—Not FDA approved for psoriasis12.Thioguanine—Not FDA approved for psoriasisFDA, Food and Drug Administration. Open table in a new tab FDA, Food and Drug Administration.

Background Head-to-head trials in psoriatic arthritis are helpful in guiding clinical decision making. The EXCEED study evaluated the efficacy and safety of secukinumab versus adalimumab as first-line biological monotherapy for 52 weeks in patients with active psoriatic arthritis, with a musculoskeletal primary endpoint of American College of Rheumatology (ACR) 20 response. Methods This parallel-group, double-blind, active-controlled, phase-3b, multicentre (168 sites in 26 countries) trial enrolled patients aged at least 18 years with active psoriatic arthritis. Eligible patients were randomly assigned (1:1) by means of interactive response technology to receive secukinumab or adalimumab. Patients, investigators, site personnel, and those doing the assessments (except independent study drug administrators) were masked to study assignment. 300 mg secukinumab was administered subcutaneously at baseline, weeks 1, 2, 3, and 4, and then every 4 weeks until week 48 as a pre-filled syringe. Adalimumab was administered every 2 weeks from baseline until week 50 as 40 mg per 0·4 mL citrate free subcutaneous injection. The primary outcome was the proportion of patients with at least 20% improvement in the ACR response criteria (ACR20) at week 52. Patients were analysed according to the treatment to which they were randomly assigned. Safety analyses included all safety data reported up to and including the week 52 visit for each patient who received at least one dose of study drug. The trial is registered at ClinicalTrials.gov, NCT02745080. Findings Between April 3, 2017 and Aug 23, 2018, we randomly assigned 853 patients to receive secukinumab (n=426) or adalimumab (n=427). 709 (83%) of 853 patients completed week 52 of the study, of whom 691 (81%) received the last study treatment at week 50. 61 (14%) of 426 patients in the secukinumab group discontinued treatment by week 52 versus 101 (24%) of 427 patients in the adalimumab group. The primary endpoint of superiority of secukinumab versus adalimumab for ACR20 response at week 52 was not met. 67% of patients in the secukinumab group achieved an ACR20 response at week 52 versus 62% of patients in the adalimumab group (OR 1·30, 95% CI 0·98–1·72; p=0·0719). The safety profiles of secukinumab and adalimumab were consistent with previous reports. Seven (2%) of 426 patients in the secukinumab group and six (1%) of 427 patients in the adalimumab group had serious infections. One death was reported in the secukinumab group due to colon cancer and was assessed as not related to the study drug by the investigator. Interpretation Secukinumab did not meet statistical significance for superiority versus adalimumab in the primary endpoint of ACR20 response at week 52. However, secukinumab was associated with a higher treatment retention rate than adalimumab. This study provides comparative data on two biological agents with different mechanisms of action, which could help guide clinical decision making in the management of patients with psoriatic arthritis. Funding Novartis Pharma.

Vitiligo is a chronic autoimmune disease resulting in skin depigmentation and reduced quality of life. There is no approved treatment for vitiligo repigmentation and current off-label therapies have limited efficacy, emphasising the need for improved treatment options. We investigated the therapeutic potential of ruxolitinib cream in patients with vitiligo and report the efficacy and safety results up to 52 weeks of double-blind treatment.We did a multicentre, randomised, double-blind, phase 2 study for adult patients with vitiligo in 26 US hospitals and medical centres in 18 states. Patients with depigmentation of 0·5% or more of their facial body surface area (BSA) and 3% or more of their non-facial BSA were randomly assigned (1:1:1:1:1) by use of an interactive response technology system to receive ruxolitinib cream (1·5% twice daily, 1·5% once daily, 0·5% once daily, or 0·15% once daily) or vehicle (control group) twice daily on lesions constituting 20% or less of their total BSA for 24 weeks. Patients in the control group in addition to patients in the 0·15% once daily group who did not show a 25% or higher improvement from baseline in facial Vitiligo Area Scoring Index (F-VASI) at week 24 were re-randomised to one of three higher ruxolitinib cream doses (0·5% once daily, 1·5% once daily, 1·5% twice daily). Patients in the 0·5% once daily, 1·5% once daily, or 1·5% twice daily groups remained at their original dose up to week 52. Patients, investigators, and the study sponsor (except members of the interim analysis and primary endpoint analysis data monitoring teams) remained masked to treatment assignment throughout the study. The primary endpoint was the proportion of patients achieving a 50% or higher improvement from baseline in F-VASI (F-VASI50) at week 24, assessed in the intention-to-treat population. The study is registered with ClinicalTrials.gov, NCT03099304.Between June 7, 2017, and March 21, 2018, 205 patients were screened for eligibility, 48 were excluded and 157 patients (mean age, 48·3 years [SD 12·9]; 73 [46%] male and 84 [54%] female) were randomly assigned to either an intervention group or the control group. 32 (20%) of 157 were assigned to the control group, 31 (20%) to the 0·15% once daily group, 31 (20%) to the 0·5% once daily group, 30 (19%) to the 1·5% once daily group, and 33 (21%) to the 1·5% twice daily group. F-VASI50 at week 24 was reached by significantly more patients given ruxolitinib cream at 1·5% twice daily (15 [45%] of 33) and 1·5% once daily (15 [50%] of 30) than were treated with vehicle (one [3%] of 32). Four patients had serious treatment-emergent adverse events (one patient in the 1·5% twice daily group developed subdural haematoma; one patient in the 1·5% once daily group had a seizure; one patient in the 0·5% once daily group had coronary artery occlusion; and one patient in the 0·5% once daily group had oesophageal achalasia), all of which were unrelated to study treatment. Application site pruritus was the most common treatment-related adverse event among patients given ruxolitinib cream (one [3%] of 33 in the 1·5% twice daily group; three [10%] of 30 in the 1·5% once daily group; three [10%] of 31 in the 0·5% once daily group; and six [19%] of 31 in the 0·15% once daily group)with three [9%] of 32 patients showing application site pruritis in the control group. Acne was noted as a treatment-related adverse event in 13 (10%) of 125 patients who received ruxolitinib cream and one (3%) of 32 patients who received vehicle cream. All treatment-related adverse events were mild or moderate in severity and similar across treatment groups.Treatment with ruxolitinib cream was associated with substantial repigmentation of vitiligo lesions up to 52 weeks of treatment, and all doses were well tolerated. These data suggest that ruxolitinib cream might be an effective treatment option for patients with vitiligo.Incyte.

Background Guselkumab, a human monoclonal antibody that binds to the p19 subunit of interleukin 23, has been approved for the treatment of moderate-to-severe psoriasis. Psoriatic arthritis is a common comorbidity of psoriasis with an umet need for novel treatments. We assessed the efficacy and safety of guselkumab in patients with active psoriatic arthritis. Methods We did a randomised, double-blind, placebo-controlled, phase 2a trial at 34 rheumatology and dermatology practices in Canada, Germany, Poland, Romania, Russia, Spain, and the USA. Eligible participants were aged 18 years or older with active psoriatic arthritis and plaque psoriasis affecting at least 3% of their body surface area, with three or more of 66 tender joints and three or more of 68 swollen joints, who had an inadequate response or intolerance to standard treatments. We randomly assigned patients (2:1) via a central interactive web-response system using computer-generated permuted blocks with a block size of six, stratified by previous anti-tumour necrosis factor-α use, to receive subcutaneous guselkumab 100 mg or placebo at week 0, week 4, and every 8 weeks thereafter for 24 weeks. Patients, investigators, and site staff were masked to treatment assignment until final database lock at week 56. At week 16, patients with less than 5% improvement in swollen and tender joint counts were eligible for early escape to ustekinumab. At week 24, the remaining placebo-treated patients crossed over to receive guselkumab 100 mg at weeks 24, 28, 36, and 44 and guselkumab-treated patients received a placebo injection at week 24, followed by guselkumab injections at weeks 28, 36, and 44. The primary endpoint was the proportion of patients with at least 20% improvement at week 24 in signs and symptoms of psoriatic arthritis according to American College of Rheumatology criteria (ACR20) in the modified intention-to-treat population (ie, all randomly assigned patients who received at least one dose of study treatment). Safety analyses included patients according to the study drug received. This study is registered with ClinicalTrials.gov, number NCT02319759. Findings Between March 27, 2015, and Jan 17, 2017, we randomly assigned 149 patients to treatment: 100 to guselkumab and 49 to placebo. 17 (35%) of 49 patients in the placebo group and ten (10%) of 100 patients in the guselkumab group were eligible for early escape to ustekinumab at week 16. 29 (59%) of 49 patients in the placebo group crossed over and received guselkumab at week 24. Three (6%) of 49 patients in the placebo group, one (3%) of 29 patients who crossed over from placebo to guselkumab, and six (6%) of 100 patients in the guselkumab group discontinued study treatment before week 44. 58 (58%) of 100 patients in the guselkumab group and nine (18%) of 49 patients in the placebo group achieved an ACR20 response at week 24 (percentage difference 39·7% [95% CI 25·3–54·1]; p<0·0001). Between week 0 and week 24, 36 (36%) of 100 guselkumab-treated patients and 16 (33%) of 49 placebo-treated patients had at least one adverse event. The most frequent adverse event was infection in both groups (16 [16%] of 100 patients in the guselkumab group vs ten [20%] of 49 patients in the placebo group). The prevalence of adverse events between week 0 and week 56 in guselkumab-treated patients (51 [40%] of 129) indicated no disproportional increase with longer guselkumab exposure. No deaths occurred. Interpretation Guselkumab, a novel anti-interleukin 23p19 antibody, significantly improved signs and symptoms of active psoriatic arthritis and was well tolerated during 44 weeks of treatment. The results of this study support further development of guselkumab as a novel and comprehensive treatment in psoriatic arthritis. Funding Janssen Research & Development.

Psoriasis is a chronic, inflammatory, multisystem disease that affects up to 3.2% of the United States population. This guideline addresses important clinical questions that arise in psoriasis management and care and provides recommendations based on the available evidence. The treatment of psoriasis with topical agents and with alternative medicine will be reviewed, emphasizing treatment recommendations and the role of dermatologists in monitoring and educating patients regarding benefits as well as risks that may be associated. This guideline will also address the severity assessment methods of psoriasis in adults. Psoriasis is a chronic, inflammatory, multisystem disease that affects up to 3.2% of the United States population. This guideline addresses important clinical questions that arise in psoriasis management and care and provides recommendations based on the available evidence. The treatment of psoriasis with topical agents and with alternative medicine will be reviewed, emphasizing treatment recommendations and the role of dermatologists in monitoring and educating patients regarding benefits as well as risks that may be associated. This guideline will also address the severity assessment methods of psoriasis in adults. DisclaimerAdherence to these guidelines will not ensure successful treatment in every situation. Furthermore, these guidelines should not be interpreted as setting a standard of care, nor should they be deemed either inclusive of all proper methods of care, or exclusive of other methods of care reasonably directed toward obtaining the same results. The ultimate judgment regarding the propriety of any specific therapy must be made by the physician and the patient in light of circumstances presented by the individual patient and the known variability and biological behavior of the disease. Furthermore, the treatment dosages used in clinical trials may not be effective in certain cases, and some patients may require shorter intervals between doses and/or higher treatment doses of a particular treatment methodology. This guideline reflects the best available data at the time the guideline was prepared. The results of future studies may require revisions to the recommendations in this guideline to reflect new data.Conflict of interest statementThe American Academy of Dermatology (AAD) strives to produce clinical guidelines that reflect the best available evidence supplemented with the judgment of expert clinicians. Significant efforts are taken to minimize the potential for conflicts of interest to influence guideline content. The management of conflict of interest for this guideline complies with the Council of Medical Specialty Societies Code of Interactions with Companies. Funding of guideline production by medical or pharmaceutical entities is prohibited, full disclosure is obtained and evaluated for all guideline contributors throughout the guideline development process, and recusal is used to manage identified relationships. The AAD conflict of interest policy summary may be viewed at www.aad.org.The information below represents the authors who disclosed a relationship with industry during guideline development. Authors (listed alphabetically) with relevant conflicts with respect to this guideline are noted with an asterisk (∗). In accordance with the AAD policy, fewer than 51% of workgroup members had any relevant conflicts of interest.Participation in one or more of the below-listed activities constitutes a relevant conflict:•service as a member of a speaker bureau, consultant, advisory board, for pharmaceutical companies on the psoriasis disease state or psoriasis drugs in development or United States (US) Food and Drug Administration (FDA) approved;•sponsored research funding or investigator-initiated studies with partial/full funding from pharmaceutical companies on the psoriasis disease state or psoriasis drugs in development or FDA approved.Draft guideline recommendations were developed through a collaborative approach between conflicted and nonconflicted section leaders. Initial recommendations were presented to the full workgroup for finalization.ScopeThis guideline will cover the use of topical agents and alternative medicine (AM) in the treatment of psoriasis in adults as well as the assessment of disease severity; psoriasis in the pediatric population will be covered in a separate guideline section, “Joint American Academy of Dermatology-National Psoriasis Foundation (NPF) guidelines of care for the management and treatment of psoriasis in pediatric patients.”1Menter A. Cordoro K.M. Davis D.M.R. et al.Joint American Academy of Dermatology-National Psoriasis Foundation guidelines of care for the management and treatment of psoriasis in pediatric patients [published correction appears in J Am Acad Dermatol. 2020;82(3):574].J Am Acad Dermatol. 2020; 82: 161-201Abstract Full Text Full Text PDF PubMed Scopus (0) Google ScholarMethodFor a full description of the methodology used herein, please refer to the Appendix section.Definition of reviewSee the Appendix for full definition statement.IntroductionPsoriasis is a common inflammatory disease, affecting approximately 3.2% of the population.2Rachakonda T.D. Schupp C.W. Armstrong A.W. Psoriasis prevalence among adults in the United States.J Am Acad Dermatol. 2014; 70: 512-516Abstract Full Text Full Text PDF PubMed Scopus (415) Google Scholar While skin involvement is the most prominent manifestation of this disease, recognition of psoriasis as a chronic, multisystem inflammatory disorder is imperative to optimize management and reduce comorbidities.Topical medications are the most common agents used to treat patients with mild to moderate psoriasis. They are frequently used as adjunctive therapies for patients on phototherapy, systemic, or biologic therapy. Alternative medicine (AM) is not typically part of conventional medical care. It may have origins outside of usual Western practice and may be desired by and benefit a subset of patients.3National Center for Complementary and Integrative HealthComplementary, Alternative, or Integrative Health: What's In a Name? NCCIH Clearinghouse.https://nccih.nih.gov/health/integrative-healthDate: 2019Date accessed: October 1, 2019Google Scholar,4van de Kerkhof P.C. Cambazard F. Hutchinson P.E. et al.The effect of addition of calcipotriol ointment (50 micrograms/g) to acitretin therapy in psoriasis.Br J Dermatol. 1998; 138: 84-89Crossref PubMed Scopus (0) Google ScholarThis section will review the assessment of psoriasis severity and the management and treatment of psoriasis with topical therapy and AM modalities in adult psoriasis patients (Table I).Table IClinical questions1.What are the efficacy, effectiveness, and adverse events of the following therapies used as monotherapy and/or combination therapy to treat psoriasis in adults?a.Topical corticosteroidsb.Calcineurin inhibitors (Topical tacrolimus and pimecrolimus)c.Vitamin D analoguesd.Tazarotenee.Moisturizersf.Salicylic acidg.Anthralinh.Coal tari.Biologic agent combinationj.Nonbiologic combinationi.Methotrexateii.Cyclosporineiii.Acitretin2.What are the efficacy, effectiveness, and adverse events of the following alternative medicines used for adult psoriasis?a.Traditional Chinese medicineb.Herbal therapiesi.Aloe veraii.St John's wortc.Diet/dietary supplementsi.Fish oilii.Vitamin Diii.Curcumin (Turmeric)iv.Zincv.Gluten-free dietd.Mind/bodyi.Hypnosisii.Stress reduction/meditation3.What is the accuracy, clinical utility, and treatment parameters for using the following severity measures to measure psoriasis severity and response to treatment?a.Body surface area (BSA)b.Psoriasis Area and Severity Index (PASI)c.Physician Global Assessment (PGA)d.PGA × BSAe.Psoriasis Symptom Inventory (PSI)f.Dermatology of Life Quality Index (DLQI)g.Pruritus assessment Open table in a new tab I. Topical agentsTopical corticosteroidsEfficacyTopical corticosteroids, which provide high efficacy and good safety, play a key role in the treatment of psoriasis, especially for localized disease. Topical corticosteroids have anti-inflammatory, antiproliferative, immunosuppressive, and vasoconstrictive effects. These effects are exerted via intracellular corticosteroid receptors, which regulate gene transcription, including several that code for proinflammatory mediators. Topical corticosteroids are classified into 7 categories based on their skin vasoconstrictive activity, ranging in strength from ultra-high (class 1) to low (class 6 and 7; Table II).5Cornell R.C. Stoughton R.B. Correlation of the vasoconstriction assay and clinical activity in psoriasis.Arch Dermatol. 1985; 121: 63-67Crossref PubMed Scopus (157) Google Scholar, 6Bolognia J. Schaffer J.V. Cerroni L. Dermatology.4th ed. Elsevier, Philadelphia2018Google Scholar, 7Gabros S. Zito P.M. Topical corticosteroids.StatPearls. Treasure Island (FL), 2019Google Scholar, 8Jacob S.E. Steele T. Corticosteroid classes: a quick reference guide including patch test substances and cross-reactivity.J Am Acad Dermatol. 2006; 54: 723-727Abstract Full Text Full Text PDF PubMed Scopus (61) Google ScholarTable IIClassification of topical corticosteroid6Bolognia J. Schaffer J.V. Cerroni L. Dermatology.4th ed. Elsevier, Philadelphia2018Google Scholar, 7Gabros S. Zito P.M. Topical corticosteroids.StatPearls. Treasure Island (FL), 2019Google Scholar, 8Jacob S.E. Steele T. Corticosteroid classes: a quick reference guide including patch test substances and cross-reactivity.J Am Acad Dermatol. 2006; 54: 723-727Abstract Full Text Full Text PDF PubMed Scopus (61) Google Scholar∗Reprinted from Dermatology: 2-Volume Set, 4th Edition, Jean Bolognia, Julie Schafer, and Lorenzo Cerroni, Glucocorticosteroids, Page No. 2190, Copyright 2018, with permission from Elsevier.WHO potency groupClassificationTopical corticosteroidSuper-potentUltrahighClass 11.Augmented betamethasone dipropionate 0.05%aOintment.,bGel.2.Clobetasol propionate 0.05%aOintment.,bGel.,cCream.,dLotion.,eFoam.,fSolution.,gScalp solution application, in some classifications class 2.,hSpray.,iShampoo 0.05%.3.Desoximetasone 0.25%hSpray.4.Augmented diflorasone diacetate 0.05%aOintment.5.Fluocinonide 0.1%cCream.6.Flurandrenolide 4 μg/cm2jTape.7.Halobetasol propionate 0.05%aOintment.,cCream.HighClass 21.Amcinonide 0.1%aOintment.2.Betamethasone dipropionate 0.05%aOintment.3.Augmented betamethasone dipropionate 0.05%cCream.,dLotion.4.Desoximetasone 0.25%aOintment.,cCream.5.Desoximetasone 0.05%bGel.6.Augmented diflorasone diacetate 0.05%cCream.7.Diflorasone diacetate 0.05%aOintment.8.Fluocinonide 0.05%aOintment.,bGel.,cCream.,fSolution.9.Halcinonide 0.1%aOintment.,cCream.10.Mometasone furoate 0.1%aOintment.11.Triamcinolone acetonide 0.5%aOintment.Class 31.Amcinonide 0.1%cCream.,dLotion.2.Betamethasone dipropionate 0.05%cCream.,kLotion, depending upon classification, class 3 or 5.3.Betamethasone valerate 0.1%aOintment.4.Betamethasone valerate 0.12%lFoam, depending upon classification, class 3 or 4.5.Diflorasone diacetate 0.05%cCream.6.Fluticasone propionate 0.005%aOintment.7.Triamcinolone acetonide 0.1%aOintment.8.Triamcinolone acetonide 0.5%cCream.Moderate (medium)Class 41.Betamethasone valerate 0.12%lFoam, depending upon classification, class 3 or 4.2.Desoximetasone 0.05%cCream.3.Fluocinolone acetonide 0.025%aOintment.4.Flurandrenolide 0.05%aOintment.5.Hydrocortisone valerate 0.2%aOintment.6.Mometasone furoate 0.1%cCream.,dLotion.7.Triamcinolone acetonide 0.1%cCream.,mKenalog ointment (manufactured by APOTHECON, a Bristol-Myers Squibb Company; Princeton, NJ).8.Triamcinolone acetonide 0.2%hSpray.Class 51.Betamethasone dipropionate 0.05%kLotion, depending upon classification, class 3 or 5.2.Betamethasone valerate 0.1%cCream.,dLotion.3.Clocortolone pivalate 0.1%cCream.4.Fluocinolone acetonide 0.025%cCream.5.Fluocinolone acetonide 0.01%nOil.,oShampoo.6.Fluticasone propionate 0.05%cCream.,dLotion.7.Flurandrenolide 0.05%cCream.,dLotion.8.Hydrocortisone butyrate 0.1%aOintment.,cCream.,dLotion.,fSolution.9.Hydrocortisone probutate 0.1%cCream.10.Hydrocortisone valerate 0.2%cCream.11.Prednicarbate 0.1%aOintment.,cCream.12.Triamcinolone acetonide 0.025%aOintment.13.Triamcinolone acetonide 0.01%dLotion.LowClass 61.Alclometasone dipropionate 0.05%aOintment.,cCream.2.Betamethasone valerate 0.05%dLotion.3.Desonide 0.05%aOintment.,bGel.,cCream.,dLotion.,eFoam.4.Fluocinolone acetonide 0.01%cCream.,fSolution.5.Triamcinolone acetonide 0.025%cCream.,dLotion.Class 71.Dexamethasone sodium phosphate 0.1%cCream.2.Hydrocortisone 0.5%-2.5%aOintment.,bGel.,cCream.,dLotion.,fSolution.3.Methylprednisolone acetate 0.25%cCream.WHO, World Health Organization.∗ Reprinted from Dermatology: 2-Volume Set, 4th Edition, Jean Bolognia, Julie Schafer, and Lorenzo Cerroni, Glucocorticosteroids, Page No. 2190, Copyright 2018, with permission from Elsevier.a Ointment.b Gel.c Cream.d Lotion.e Foam.f Solution.g Scalp solution application, in some classifications class 2.h Spray.i Shampoo 0.05%.j Tape.k Lotion, depending upon classification, class 3 or 5.l Foam, depending upon classification, class 3 or 4.m Kenalog ointment (manufactured by APOTHECON, a Bristol-Myers Squibb Company; Princeton, NJ).n Oil.o Shampoo. Open table in a new tab Choosing a corticosteroid with appropriate potency plus the appropriate vehicle should be based on the disease severity, disease location, patient preference, and the age of the patient. Lower potency corticosteroids should be used on the face, intertriginous areas, and areas that are susceptible to steroid atrophy (eg, forearms) and other adverse effects. In adults, corticosteroids in classes 2 through 5 (moderate to high potency; Table II) are generally recommended as initial therapy. Areas with thick, chronic plaques often require treatment with class 1 (ultrahigh-potency) corticosteroids. In numerous randomized controlled trials (RCTs), different potency topical corticosteroids were effective and safe at 2 to 4 weeks in the treatment of mild to severe plaque psoriasis.9Bernhard J. Whitmore C. Guzzo C. et al.Evaluation of halobetasol propionate ointment in the treatment of plaque psoriasis: report on two double-blind, vehicle-controlled studies.J Am Acad Dermatol. 1991; 25: 1170-1174Abstract Full Text PDF PubMed Scopus (30) Google Scholar, 10Gottlieb A.B. Ford R.O. Spellman M.C. The efficacy and tolerability of clobetasol propionate foam 0.05% in the treatment of mild to moderate plaque-type psoriasis of nonscalp regions.J Cutan Med Surg. 2003; 7: 185-192Crossref PubMed Google Scholar, 11Lebwohl M. Sherer D. Washenik K. et al.A randomized, double-blind, placebo-controlled study of clobetasol propionate 0.05% foam in the treatment of nonscalp psoriasis.Int J Dermatol. 2002; 41: 269-274Crossref PubMed Scopus (48) Google Scholar Evidence on the efficacy of topical corticosteroids from RCTs varies due to the differences in study designs, patient populations, and end points, making it difficult to do an accurate statistical comparison of the majority of published studies.For ultrahigh-potency (class 1) corticosteroids, the efficacy rates in several RCTs vary from 58% to 92%.9Bernhard J. Whitmore C. Guzzo C. et al.Evaluation of halobetasol propionate ointment in the treatment of plaque psoriasis: report on two double-blind, vehicle-controlled studies.J Am Acad Dermatol. 1991; 25: 1170-1174Abstract Full Text PDF PubMed Scopus (30) Google Scholar,10Gottlieb A.B. Ford R.O. Spellman M.C. The efficacy and tolerability of clobetasol propionate foam 0.05% in the treatment of mild to moderate plaque-type psoriasis of nonscalp regions.J Cutan Med Surg. 2003; 7: 185-192Crossref PubMed Google Scholar,12Camarasa J.M. Ortonne J.P. Dubertret L. Calcitriol shows greater persistence of treatment effect than betamethasone dipropionate in topical psoriasis therapy.J Dermatolog Treat. 2003; 14: 8-13Crossref PubMed Scopus (41) Google Scholar,13Keegan B.R. Desoximetasone 0.25% spray for the relief of scaling in adults with plaque psoriasis.J Drugs Dermatol. 2015; 14: 835-840PubMed Google Scholar In a double-blind, vehicle-controlled trial of 204 patients with moderate to severe psoriasis, after 2 weeks of treatment, the halobetasol propionate ointment (class 1) group improved the Physician's Global Assessment (PGA) scores by 92% compared with 39% in vehicle-treated patients (P < .0003).9Bernhard J. Whitmore C. Guzzo C. et al.Evaluation of halobetasol propionate ointment in the treatment of plaque psoriasis: report on two double-blind, vehicle-controlled studies.J Am Acad Dermatol. 1991; 25: 1170-1174Abstract Full Text PDF PubMed Scopus (30) Google Scholar An RCT of 279 patients with mild to moderate psoriasis found that after 2 weeks of treatment with clobetasol foam (class 1), 68% of patients achieved a Physician's Static Global Assessment (PSGA) score of 0 or 1 compared with 21% of patients treated with vehicle (P < .0001).10Gottlieb A.B. Ford R.O. Spellman M.C. The efficacy and tolerability of clobetasol propionate foam 0.05% in the treatment of mild to moderate plaque-type psoriasis of nonscalp regions.J Cutan Med Surg. 2003; 7: 185-192Crossref PubMed Google Scholar Another double-blind RCT of 81 patients used the Investigator Global Assessment scale to assess patients with mild to moderate psoriasis and demonstrated that after 2 weeks of treatment with clobetasol foam (class 1), 58% of patients achieved moderate or marked improvement, or almost or completely clear psoriasis compared with 15% in vehicle-treated patients (P < .0005).11Lebwohl M. Sherer D. Washenik K. et al.A randomized, double-blind, placebo-controlled study of clobetasol propionate 0.05% foam in the treatment of nonscalp psoriasis.Int J Dermatol. 2002; 41: 269-274Crossref PubMed Scopus (48) Google ScholarFor high-potency (class 2 and 3) corticosteroids, the efficacy rates in several RCTs vary from 68% to 74%. In a double blind-RCT of 35 patients with psoriasis treated with 0.25% desoximetasone cream (class 2) for 3 weeks, 68% of the desoximetasone group compared with 23% of the vehicle group achieved improvement in their mean overall evaluation scores (P < .001).14Savin R.C. Desoximetasone—a new topical corticosteroid: short-and long-term experiences.Cutis. 1978; 21: 403-407PubMed Google Scholar Two RCTs with fluticasone propionate 0.005%, a class 3 corticosteroid, showed 68% to 69% of patients with moderate to severe psoriasis in the treatment group achieved, good, excellent, or clear skin after 4 weeks compared with 29% to 30% in the vehicle group (P = .00001).15Olsen E.A. Efficacy and safety of fluticasone propionate 0.005% ointment in the treatment of psoriasis.Cutis. 1996; 57: 57-61PubMed Google ScholarFor moderate-potency (class 4 and 5) corticosteroids, the efficacy rates in several RCTs vary from 70% to 83%.16Pauporte M. Maibach H. Lowe N. et al.Fluocinolone acetonide topical oil for scalp psoriasis.J Dermatolog Treat. 2004; 15: 360-364Crossref PubMed Scopus (33) Google Scholar,17Stein L.F. Sherr A. Solodkina G. Gottlieb A.B. Chaudhari U. Betamethasone valerate foam for treatment of nonscalp psoriasis.J Cutan Med Surg. 2001; 5: 303-307Crossref PubMed Google Scholar An RCT of 40 patients with nonscalp psoriasis revealed that 70% of patients treated with betamethasone valerate foam 0.12% (class 4) achieved greater than 50% improvement compared with 24% of patients in the placebo group after 12 weeks of treatment (P < .001).17Stein L.F. Sherr A. Solodkina G. Gottlieb A.B. Chaudhari U. Betamethasone valerate foam for treatment of nonscalp psoriasis.J Cutan Med Surg. 2001; 5: 303-307Crossref PubMed Google Scholar In an RCT of patients with moderate to severe scalp psoriasis, the group treated with fluocinolone acetonide 0.01% oil (class 5 corticosteroid) had a higher proportion of patients achieving good or better improvement from baseline compared with the vehicle-treated group after 3 weeks of treatment (83% vs 36%; P < .001).16Pauporte M. Maibach H. Lowe N. et al.Fluocinolone acetonide topical oil for scalp psoriasis.J Dermatolog Treat. 2004; 15: 360-364Crossref PubMed Scopus (33) Google Scholar Additionally, an RCT showed that fluticasone propionate 0.05% cream (class 5) was superior to hydrocortisone butyrate 0.1% cream (class 7) in achieving clearance, excellent, or good treatment response after 3 weeks of treatment (79% vs 68%; P < .05).18James M. A randomized, double-blind, multicenter trial comparing fluticasone propionate cream, 0.05%, and hydrocortisone-17-butyrate cream, 0.1%, applied twice daily for 4 weeks in the treatment of psoriasis.Cutis. 2001; 67: 2-9PubMed Google ScholarOwing to the inconsistent criteria in RCT design, comparisons between different corticosteroids and classes are complex. Nevertheless, a systematic review of topical corticosteroids for the treatment of psoriasis revealed that potent and super-potent topical corticosteroids were more efficacious than mild or moderately potent corticosteroids.19Mason J. Mason A.R. Cork M.J. Topical preparations for the treatment of psoriasis: a systematic review.Br J Dermatol. 2002; 146: 351-364Crossref PubMed Scopus (141) Google ScholarTreatment of psoriasis in intertriginous areas, such as the groin, or hair-bearing skin, such as the scalp, can be challenging due to the difficulty of applying a topical product to these areas based on the vehicle selection. Therefore, appropriate selection of the vehicle depending on hair density and individual hairstyles and preferences is essential for the efficacy of the treatment. Several RCTs and systematic reviews of scalp psoriasis treatment demonstrate the safety and efficacy of various potency topical corticosteroids used for 3 to 12 weeks.16Pauporte M. Maibach H. Lowe N. et al.Fluocinolone acetonide topical oil for scalp psoriasis.J Dermatolog Treat. 2004; 15: 360-364Crossref PubMed Scopus (33) Google Scholar,17Stein L.F. Sherr A. Solodkina G. Gottlieb A.B. Chaudhari U. Betamethasone valerate foam for treatment of nonscalp psoriasis.J Cutan Med Surg. 2001; 5: 303-307Crossref PubMed Google Scholar,20Mason A.R. Mason J.M. Cork M.J. Hancock H. Dooley G. Topical treatments for chronic plaque psoriasis of the scalp: a systematic review.Br J Dermatol. 2013; 169: 519-527Crossref PubMed Scopus (22) Google Scholar The duration of the therapy depends on factors such as the strength of topical corticosteroids, the severity of the disease, anatomic location, and age of the patient. Similarly, a steroid-sparing agent can be considered to avoid adverse effects.Additionally, intralesional corticosteroids can be used for localized nonresponding or very thick lesions on glabrous skin, scalp, nails, palms, and soles. Several studies and reports have shown that intralesional corticosteroids can be effective for the treatment of psoriasis.21Richards R.N. Update on intralesional steroid: focus on dermatoses.J Cutan Med Surg. 2010; 14: 19-23Crossref PubMed Scopus (20) Google Scholar, 22Chan C.S. Van Voorhees A.S. Lebwohl M.G. et al.Treatment of severe scalp psoriasis: from the Medical Board of the National Psoriasis Foundation.J Am Acad Dermatol. 2009; 60: 962-971Abstract Full Text Full Text PDF PubMed Scopus (0) Google Scholar, 23Handa S. Newer trends in the management of psoriasis at difficult to treat locations: scalp, palmoplantar disease and nails.Indian J Dermatol Venereol Leprol. 2010; 76: 634-644Crossref PubMed Scopus (16) Google Scholar Triamcinolone acetonide in a dose up to 20 mg/mL can be used every 3 to 4 weeks.24Kenalog®-10 Injection (triamcinolone acetonide injectable suspension, USP) [package insert]. Bristol-Myers Squibb Company, Princeton, NJ2018https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/012041s045lbl.pdfDate accessed: April 23, 2020Google Scholar The injection volume varies pending lesional size and the area affected.Risks/harms and benefitsThe most common local skin adverse effects of topical corticosteroid use include skin atrophy, striae, folliculitis, telangiectasia, and purpura.25Abraham A. Roga G. Topical steroid-damaged skin.Indian J Dermatol. 2014; 59: 456-459Crossref PubMed Scopus (31) Google Scholar Face and intertriginous areas, as well as chronically treated areas, especially forearms, are at greatest risk to develop these adverse effects. Topical corticosteroids may exacerbate acne, rosacea, perioral dermatitis, and tinea infections and may occasionally cause contact dermatitis. Rebound (ie, when the disease recurs and is more severe than before treatment) can occur from abrupt withdrawal of topical corticosteroids, although the frequency and severity of this phenomenon are unknown. The daily use of ultrahigh- and high-potency (class 1-3) corticosteroids for up to 4 weeks is generally safe with minimal risk of skin atrophy.26Castela E. Archier E. Devaux S. et al.Topical corticosteroids in plaque psoriasis: a systematic review of risk of adrenal axis suppression and skin atrophy.J Eur Acad Dermatol Venereol. 2012; 26: 47-51Crossref PubMed Scopus (0) Google ScholarRisk of hypothalamic pituitary adrenal axis suppression from the use of topical corticosteroids for extensive plaque or scalp psoriasis has been reported to be low.26Castela E. Archier E. Devaux S. et al.Topical corticosteroids in plaque psoriasis: a systematic review of risk of adrenal axis suppression and skin atrophy.J Eur Acad Dermatol Venereol. 2012; 26: 47-51Crossref PubMed Scopus (0) Google Scholar In a systematic review of 13 randomized studies, studies performed for up to 4 weeks found the percentage of patients with a reduction in the morning cortisol level was 0% with halobetasol or fluocinonide, 0% to 48% with clobetasol propionate, and 0% to 18% with betamethasone dipropionate. Nevertheless, results of adrenocorticotropic hormone stimulation tests, the gold standard for assessing hypothalamic-pituitary-adrenal axis suppression, were always within normal reference ranges, even when assessed after 6 to 12 months of topical corticosteroid use.26Castela E. Archier E. Devaux S. et al.Topical corticosteroids in plaque psoriasis: a systematic review of risk of adrenal axis suppression and skin atrophy.J Eur Acad Dermatol Venereol. 2012; 26: 47-51Crossref PubMed Scopus (0) Google Scholar Rare systemic adverse effects include Cushing syndrome and osteonecrosis of the femoral head.27Takahashi H. Tsuji H. Honma M. Ishida-Yamamoto A. Iizuka H. Femoral head osteonecrosis after long-term topical corticosteroid treatment in a psoriasis patient.J Dermatol. 2012; 39: 887-888Crossref PubMed Scopus (0) Google Scholar,28el Maghraoui A. Tabache F. Bezza A. Ghafir D. Ohayon V. Archane M.I. Femoral head osteonecrosis after topical corticosteroid therapy.Clin Exp Rheumatol. 2001; 19: 233PubMed Google Scholar Topical products that contain corticosteroid should not be used for more than 12 weeks for nail disease, because there are isolated reports of bone atrophy with persistent use.29Malec-Milewska M. Sekowska A. Koleda I. Horosz B. Guc M. Jastrzebski J. Sympathetic nerve blocks for the management of postherpetic neuralgia-19 years of pain clinic experience.Anaesthesiol Intensive Ther. 2014; 46: 255-261Crossref PubMed Scopus (3) Google Scholar,30Rigopoulos D. Gregoriou S. Daniel Iii, C.R. et al.Treatment of nail psoriasis with a two-compound formulation of calcipotriol plus betamethasone dipropionate ointment.Dermatology. 2009; 218: 338-341Crossref PubMed Scopus (36) Google Scholar Increased intraocular pressure, glaucoma, and cataracts have been rarely reported with the use of topical corticosteroids around the eye.31Garrott H.M. Walland M.J. Glaucoma from topical corticosteroids to the eyelids.Clin Exp Ophthalmol. 2004; 32: 224-226Crossref PubMed Scopus (38) Google Scholar,32Day A. Abramson A.K. Patel M. Warren R.B. Menter M.A. The spectrum of oculocutaneous disease: part II. Neoplastic and drug-related causes of oculocutaneous disease.J Am Acad Dermatol. 2014; 70: 821.e-821.e19Abstract Full Text Full Text PDF Scopus (3) Google Scholar In rare cases, type 2 diabetes has been reported with topical corticosteroid use.33Andersen Y.M.F. Egeberg A. Ban L. et al.Association between topical corticosteroid use and type 2 diabetes in two European population-based adult cohorts.Diabetes Care. 2019; 42: 1095-1103Crossref PubMed Scopus (11) Google ScholarDespite the safety data,26Castela E. Archier E. Devaux S. et al.Topical corticosteroids in plaque psoriasis: a systematic review of risk of adrenal axis suppression and skin atrophy.J Eur Acad Dermatol Venereol. 2012; 26: 47-51Crossref PubMed Scopus (0) Google Scholar caution is advised, because the greatest risk for systemic adverse effects occurs when ultrahigh- or high-potency corticosteroids are used over a large surface (>20% body surface area [BSA]) or under occlusion for a prolonged period (>4 weeks) . Clinicians should consider limiting the use of class 1 corticosteroids to no more than twice daily for up to 4 weeks, when possible.34Clobex® [package insert]. Galderma Laboratories, L.P., Fort Worth, TX2012https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/021535Orig1s003,%20021644Orig1s003lbl.pdfDate accessed: October 17, 2019Google Scholar In the event of a flare, repeated courses of a class 1 corticosteroid can be administered. Longer durations of class 1 corticosteroid therapy for psoriasis of the palms and soles are acceptable with close attention to the development of potential adverse effects. Gradual reduction in the frequency of use after clinical improvement is recommended, but the exact details of this tapering are not well established. Topical corticosteroids can be tapered off by reducing use to every other day, then eventually 2 times a week, and finally discontinuation if psoriasis is well controlled and stable during the whole process. T

Psoriasis is a chronic, multisystem, inflammatory disease that affects approximately 1% of children, with onset most common during adolescence. This guideline addresses important clinical questions that arise in psoriasis management and provides evidence-based recommendations. Attention will be given to pediatric patients with psoriasis, recognizing the unique physiology, pharmacokinetics, and patient-parent-provider interactions of patients younger than 18 years old. The topics reviewed here mirror those discussed in the adult guideline sections, excluding those topics that are irrelevant to, or lack sufficient information for, pediatric patients.

Dual neutralisation of interleukin 17A (IL17A) and interleukin 17F (IL17F) is a potential novel therapeutic approach in psoriatic arthritis. We assessed bimekizumab, a monoclonal antibody that selectively neutralises IL17A and IL17F, in patients with active psoriatic arthritis.BE ACTIVE was a randomised, double-blind, placebo-controlled, dose-ranging phase 2b study done at 41 sites in the Czech Republic, Germany, Hungary, Poland, Russia, and the USA. Eligible patients aged 18 years or older with active adult-onset psoriatic arthritis and symptoms for at least 6 months were randomly assigned (1:1:1:1:1) to placebo, 16 mg bimekizumab, 160 mg bimekizumab, 160 mg bimekizumab with a one-off 320 mg loading dose, or 320 mg bimekizumab, which were administered as subcutaneous injections every 4 weeks for 12 weeks. After 12 weeks, patients assigned to the placebo and 16 mg bimekizumab groups were randomly reassigned (1:1) to either 160 mg or 320 mg bimekizumab, and all other patients remained on their originally assigned initial dose up to 48 weeks. Both participants and researchers were blinded to treatment allocation in the first 12 weeks, and blinded to the dose of bimekizumab thereafter. The primary endpoint was the proportion of patients with at least 50% improvement in the American College of Rheumatology response criteria at week 12, which was assessed in all patients who received at least one dose of study treatment and had a valid measurement of the primary efficacy endpoint at baseline. The trial, including all follow-up, has been completed. This trial is registered with ClinicalTrials.gov, NCT02969525.Between Oct 27, 2016, and July 16, 2018, 308 patients were screened, and 206 were randomly assigned: 42 to the placebo group, and 41 each to the four bimekizumab groups. At 12 weeks, compared with the placebo group, significantly more patients in the 16 mg bimekizumab (odds ratio [OR] 4·2 [95% CI 1·1-15·2]; p=0·032), 160 mg bimekizumab (8·1 [2·3-28·7]; p=0·0012), and 160 mg (loading dose) bimekizumab (9·7 [2·7-34·3]; p=0·0004) groups achieved an ACR50 response. At 12 weeks, 24 (57%) of 42 patients in the placebo group and 68 (41%) of the 164 patients in the bimekizumab groups reported treatment-emergent adverse events. Most of these adverse events were mild or moderate. Serious treatment-emergent adverse events occurred in nine patients, eight of whom were receiving bimekizumab. No deaths or cases of inflammatory bowel disease were reported.Bimekizumab doses of 16 mg and 160 mg (with or without a 320 mg loading dose) were associated with significant improvements in ACR50 compared with placebo, with an acceptable safety profile. Our results support phase 3 investigation of bimekizumab as a treatment for psoriatic arthritis.UCB Pharma.

Patients with psoriasis value rapid and complete skin clearance. No head‐to‐head studies have focused on early responses to interleukin (IL)‐17 vs. IL‐23 inhibitors. To compare early and complete skin clearance by the IL‐17A inhibitor ixekizumab vs. the IL‐23p19 inhibitor guselkumab. IXORA‐R, a 24‐week, randomized, double‐blinded study, enrolled adults with moderate‐to‐severe plaque psoriasis [static Physician's Global Assessment of Disease (sPGA) score of ≥ 3, Psoriasis Area and Severity Index (PASI) ≥ 12, and ≥ 10% body surface area]. Patients were randomized (1 : 1) to receive the approved dose of subcutaneous ixekizumab or guselkumab. Primary end point was 100% improvement in PASI (PASI 100) at week 12. Major secondary end points included other levels of improved PASI and sPGA at different time points. Comparisons were made using the Cochran–Mantel–Haenszel test with a multiple testing strategy. Nonresponder imputation was used for missing data. After the completion of the study, the final secondary end point (PASI 100 at 24 weeks) and safety data through week 24 will be reported. In total, 1027 patients were randomized. The primary end point PASI 100 at week 12 was met [215/520 ixekizumab (41%); 126/507 guselkumab (25%); P < 0·001]. All major secondary end points measured up to week 12 were met, including PASI 50 at week 1 and PASI 75 at week 2. Serious adverse event frequency was 3% for each group; no new safety signals were identified. Ixekizumab was superior to guselkumab for rapidly improving signs and symptoms in patients with moderate‐to‐severe plaque psoriasis by week 12. Adverse events were similar to previous ixekizumab and guselkumab studies. Compared with the IL‐23 inhibitor guselkumab, ixekizumab can offer complete skin clearance more rapidly to patients with moderate‐to‐severe plaque psoriasis. What's already known about this topic? Patients with plaque psoriasis desire both high levels of clearance and rapid onset of treatment effects. Ixekizumab, a high‐affinity monoclonal antibody that selectively targets interleukin (IL)‐17A, has demonstrated greater and faster skin clearance than etanercept and ustekinumab, with consistent long‐term efficacy, safety and durability of response. Clinical trial data and systematic reviews have suggested that IL‐17 inhibitors can improve a patient's psoriasis more rapidly than IL‐23 inhibitors. What does this study add? The head‐to‐head study design directly compares the efficacy and speed of response of ixekizumab and the IL‐23 inhibitor guselkumab in moderate‐to‐severe plaque psoriasis. The primary end point was met, showing superiority of ixekizumab over guselkumab for achieving complete skin clearance at week 12. The safety profile of ixekizumab was consistent with previous studies. Ixekizumab can deliver patients complete skin clearance and improved quality of life more rapidly than guselkumab.

Few therapeutic options are available for patients with moderate-to-severe hidradenitis suppurativa. We aimed to assess the efficacy of secukinumab in patients with moderate-to-severe hidradenitis suppurativa in two randomised trials.SUNSHINE and SUNRISE were identical, multicentre, randomised, placebo-controlled, double-blind phase 3 trials done in 219 primary sites in 40 countries. Patients aged 18 years old or older with the capacity to provide written informed consent and with moderate-to-severe hidradenitis suppurativa (defined as a total of ≥5 inflammatory lesions affecting ≥2 distinct anatomical areas) for at least 1 year were eligible for inclusion. Included patients also agreed to daily use of topical over-the-counter antiseptics on the areas affected by hidradenitis suppurativa lesions while on study treatment. Patients were excluded if they had 20 or more fistulae at baseline, had ongoing active conditions requiring treatment with prohibited medication (eg, systemic biological immunomodulating treatment, live vaccines, or other investigational treatments), or met other exclusion criteria. In both trials, patients were randomly assigned (1:1:1) by means of interactive response technology to receive subcutaneous secukinumab 300 mg every 2 weeks, subcutaneous secukinumab 300 mg every 4 weeks, or subcutaneous placebo all via a 2 mL prefilled syringe in a double-dummy method as per treatment assignment. The primary endpoint was the proportion of patients with a hidradenitis suppurativa clinical response, defined as a decrease in abscess and inflammatory nodule count by 50% or more with no increase in the number of abscesses or in the number of draining fistulae compared with baseline, at week 16, assessed in the overall population. Hidradenitis suppurativa clinical response was calculated based on the number of abscesses, inflammatory nodules, draining fistulae, total fistulae, and other lesions in the hidradenitis suppurativa affected areas. Safety was assessed by evaluating the presence of adverse events and serious adverse events according to common terminology criteria for adverse events, which were coded using Medical Dictionary for Regulatory Activities terminology. Both the SUNSHINE, NCT03713619, and SUNRISE, NCT03713632, trials are registered with ClinicalTrials.gov.Between Jan 31, 2019, and June 7, 2021, 676 patients were screened for inclusion in the SUNSHINE trial, of whom 541 (80%; 304 [56%] women and 237 [44%] men; mean age 36·1 years [SD 11·7]) were included in the analysis (181 [33%] in the secukinumab every 2 weeks group, 180 [33%] in the secukinumab every 4 weeks group, and 180 [33%] in the placebo group). Between the same recruitment dates, 687 patients were screened for inclusion in the SUNRISE trial, of whom 543 (79%; 306 [56%] women and 237 [44%] men; mean age 36·3 [11·4] years) were included in the analysis (180 [33%] in the secukinumab every 2 weeks group, 180 [33%] in the secukinumab every 4 weeks group, and 183 [34%] in the placebo group). In the SUNSHINE trial, significantly more patients in the secukinumab every 2 weeks group had a hidradenitis suppurativa clinical response (rounded average number of patients with response in 100 imputations, 81·5 [45%] of 181 patients) compared with the placebo group (60·7 [34%] of 180 patients; odds ratio 1·8 [95% CI 1·1-2·7]; p=0·0070). However, there was no significant difference between the number of patients in the secukinumab every 4 weeks group (75·2 [42%] of 180 patients) and the placebo group (1·5 [1·0-2·3]; p=0·042). Compared with the placebo group (57·1 [31%] of 183 patients), significantly more patients in the secukinumab every 2 weeks group (76·2 [42%] of 180 patients; 1·6 [1·1-2·6]; p=0·015) and the secukinumab every 4 weeks group (83·1 [46%] of 180 patients; 1·9 [1·2-3·0]; p=0·0022) had a hidradenitis suppurativa clinical response in the SUNRISE trial. Patient responses were sustained up to the end of the trials at week 52. The most common adverse event by preferred term up to week 16 was headache in both the SUNSHINE (17 [9%] patients in the secukinumab every 2 weeks group, 20 [11%] in the secukinumab every 4 weeks group, and 14 [8%] in the placebo group) and SUNRISE (21 [12%] patients in the secukinumab every 2 weeks group, 17 [9%] in the secukinumab every 4 weeks group, and 15 [8%] in the placebo group) trials. No study-related deaths were reported up to week 16. The safety profile of secukinumab in both trials was consistent with that previously reported, with no new or unexpected safety findings detected.When given every 2 weeks, secukinumab was clinically effective at rapidly improving signs and symptoms of hidradenitis suppurativa with a favourable safety profile and with sustained response up to 52 weeks of treatment.Novartis Pharma.

Bimekizumab is a monoclonal IgG1 antibody that selectively inhibits interleukin (IL)-17A and IL-17F. We assessed the efficacy and safety of bimekizumab in patients with active psoriatic arthritis who were naive to biologic disease-modifying antirheumatic drugs (DMARDs).BE OPTIMAL was a 52-week, phase 3, multicentre, randomised, double-blind, placebo-controlled, active reference (adalimumab) trial done at 135 sites (hospitals, clinics, doctors' offices, and research centres) in 14 countries. Eligible patients were 18 years or older with a documented diagnosis of adult-onset psoriatic arthritis that met the Classification Criteria for Psoriatic Arthritis for at least 6 months before screening. Participants were randomly assigned with an interactive-voice and web-response system on the basis of a predetermined randomisation schedule (3:2:1, stratified by region and bone erosion number at baseline) to bimekizumab 160 mg every 4 weeks, placebo every 2 weeks, or the reference group (adalimumab 40 mg every 2 weeks), all administered subcutaneously. At week 16, patients randomly assigned to placebo switched to bimekizumab 160 mg every 4 weeks. The primary endpoint was the proportion of patients reaching 50% or greater improvement in American College of Rheumatology criteria (ACR50) at week 16 (non-responder imputation). Efficacy analyses included all patients who were randomly assigned (intention-to-treat population); the safety analysis set comprised patients who received one or more doses of treatment. Data are presented to week 24 (preplanned analysis). This trial is registered at ClinicalTrials.gov, NCT03895203.Between April 3, 2019, and Oct 25, 2021, 1163 patients were screened and 852 were randomly assigned to bimekizumab (n=431), placebo (n=281), and reference (adalimumab; n=140) groups. At week 16, significantly more patients receiving bimekizumab (189 [44%] of 431) reached ACR50 response versus placebo (28 [10%] of 281; odds ratio 7·1 [95% CI 4·6-10·9], p<0·0001; adalimumab 64 [46%] of 140). All secondary hierarchical endpoints were met. Treatment-emergent adverse events up to week 16 were reported in 258 [60%] of 431 patients receiving bimekizumab, 139 [49%] of 281 patients receiving placebo, and 83 [59%] of 140 patients receiving adalimumab. No deaths occurred.Bimekizumab treatment had superior improvements in joint, skin, and radiographic efficacy outcomes at week 16 compared with placebo in patients with psoriatic arthritis who were naive to biologic DMARDs. The safety profile of bimekizumab, including the occurrence of fungal infections, was consistent with previous phase 3 studies in patients with plaque psoriasis, and with IL-17A inhibitors.UCB Pharma.

To assess long-term efficacy and safety of guselkumab, an interleukin-23 p19 subunit (IL-23p19) inhibitor, in patients with active psoriatic arthritis (PsA) from the phase III DISCOVER-2 trial.In the DISCOVER-2 trial, patients with active PsA (≥5 swollen joints and ≥5 tender joints; C-reactive protein level ≥0.6 mg/dl) despite prior nonbiologic therapy were randomized to receive the following: guselkumab 100 mg every 4 weeks; guselkumab 100 mg at weeks 0 and 4 and then every 8 weeks; or placebo with crossover to guselkumab 100 mg every 4 weeks, beginning at week 24. Efficacy assessments included American College of Rheumatology ≥20%/50%/70% improvement criteria (ACR20/50/70), Investigator's Global Assessment (IGA) of psoriasis score of 0 (indicating complete skin clearance), resolution of enthesitis (Leeds Enthesitis Index) and dactylitis (Dactylitis Severity Score), and changes in the Sharp/van der Heijde modified radiographic scores for PsA. Clinical data (imputed as no response/no change from baseline if missing) and observed radiographic data were summarized through week 100; safety assessments continued through week 112.Of the 739 randomized and treated patients, 652 (88%) completed treatment through week 100. Across groups of guselkumab-treated patients (including those in the placebo-guselkumab crossover group), the following findings at week 100 indicated that amelioration of arthritis signs/symptoms and extraarticular manifestations was durable through 2 years: ACR20 response (68-76%), ACR50 response (48-56%), ACR70 response (30-36%), IGA score of 0 (55-67%), enthesitis resolution (62-70%), and dactylitis resolution (72-83%). Mean changes in the Sharp/van der Heijde modified score for PsA from weeks 52 to week 100 (range 0.13-0.75) indicated that the low rates of radiographic progression observed among guselkumab-treated patients at earlier time points extended through week 100. Through week 112, 8% (5.8 per 100 patient-years) and 3% (1.9 per 100 patient-years) of the 731 guselkumab-treated patients had a serious adverse event or serious infection, respectively; 1 death occurred (road traffic accident).In biologic-naive PsA patients, guselkumab provided durable improvements in multiple disease domains with no unexpected safety findings through 2 years.

The potential therapeutic activity of a human monoclonal antibody to the human interleukin-12 p40 subunit (anti-IL-12p40) has been established both in vitro and in vivo, warranting a first-in-human investigation in psoriasis. This phase I, first-in-human, non-randomized, open-label study evaluated the short-term safety, pharmacokinetics, and clinical response of single, ascending, intravenous (IV) doses of anti-IL-12p40 in subjects with moderate-to-severe psoriasis vulgaris. Eighteen subjects with at least 3% body surface area involvement were enrolled in four dose groups (0.1, 0.3, 1.0, and 5.0 mg per kg). Safety, pharmacokinetics, and clinical response (e.g., Psoriasis Area and Severity Index (PASI)) were monitored at baseline and at specific time points over a 16-wk follow-up period. Anti-IL-12p40 was generally well tolerated. No related serious adverse events or infusion reactions were reported, and most adverse events were mild. IV anti-IL-12p40 yielded linear pharmacokinetics, with a mean terminal half-life of approximately 24 d. Dose-dependent associations with both the rate and extent of clinical response were observed across the four dose groups. Twelve of 18 subjects (67%) achieved at least a 75% improvement in PASI between 8 and 16 wk after study agent administration. Significant and sustained concentration-dependent improvements in psoriatic lesions were observed in most subjects.

Skin irradiation with ultraviolet B (UVB) is a common and often durable treatment for psoriasis and other inflammatory skin disorders. We studied the effects of UVB on keratinocytes and leukocytes in psoriatic tissue and in culture. In nine patients treated repetitively, most of the cellular and molecular changes that typify the psoriatic epidermis reverted to normal. Keratinocyte hyperplasia, assessed by expression of the Ki-67 cell cycle antigen, decreased by 70%, and residual cell proliferation was appropriately confined to the basal layer. Epidermal thickening was reduced by 60%, and a granular layer reformed. Expression of keratin 16, as well as suprabasal integrin alpha 3 and insulin-like growth factor-1 receptors, was eliminated, whereas filagrin increased markedly. UVB also depleted &amp;gt; 90% of the CD3+, CD8+, and CD25+ T cells from the psoriatic epidermis, whereas dermal T cells were only minimally depressed. The latter finding parallels the known inability of these doses of UVB to penetrate the dermis. In tissue culture, UVB was antiproliferative and cytotoxic toward T cells and keratinocytes, but the T cells were 10-fold more sensitive. Furthermore, low doses of UVB induced apoptosis in lymphocytes but not keratinocytes, as detected by the TUNEL (TdT-mediated dUTP-biotin nick end labeling) technique. The selective effects of UVB on intraepidermal T cells in situ and in culture support the hypothesis that epidermal alterations in psoriasis can be normalized by a depletion of activated intraepidermal T cells.

The presence of Ia-like antigens was demonstrated on a small population (2-6%) of highly purified human circulating T lymphocytes by immunofluorescence with a rabbit anti-Ia serum raised against the isolated bimolecular Ia structure. The Ia+ T lymphocytes have no surface or intracellular immunoglobulins. The expansion of this Ia+ T-cell population was encountered in certain patients. Ia antigens were also found on T blasts grown in long-term cultures with conditioned medium generated by phytohemagglutinin-stimulated lymphocytes. In addition, leukemia blasts which stained for Ia antigens and formed E rosettes were identified in the peripheral blood of two leukemic patients. This evidence further supports the existence of Ia-bearing T cells in man. The Ia+ T-lymphocyte population was shown to contain cells responsible for the generation of allogeneic helper activity. Elimination of Ia+ lymphocytes from a purified T-cell population by the anti-Ia antiserum and complement abolished its ability to help an allogeneic B-cell preparation to generate plaque-forming cells against sheep erythrocytes in vitro in the presence of the antigen.

<h3>Background</h3> Leukocyte function–associated antigen 1 (LFA-1), consisting of CD11a and CD18 subunits, plays an important role in T-cell activation and leukocyte extravasation. <h3>Objective</h3> To test whether blocking CD11a decreases immunobiologic and clinical activity in psoriatic plaques. <h3>Design</h3> Open-label, multicenter, dose escalation study. <h3>Patients</h3> Thirty-nine patients with moderate-to-severe psoriasis. <h3>Intervention</h3> Intravenous infusions of efalizumab, a humanized anti-CD11a monoclonal antibody, for 7 weeks at doses of 0.1 mg/kg every other week or 0.1 mg/kg weekly (category 1), 0.3 mg/kg weekly (category 2), and 0.3 increasing to 0.6 or 1.0 mg/kg weekly (category 3). Skin biopsies were performed on days 0, 28, and 56. <h3>Main Outcome Measures</h3> Serum efalizumab levels, levels of total and unoccupied T-cell CD11a, T cell counts, epidermal thickness, cutaneous intercellular adhesion molecule 1 (ICAM-1) and keratin 16 (K16) expression, Psoriasis Area and Severity Index (PASI) scores. <h3>Results</h3> Dose-response relationships were observed for pharmacokinetics and pharmacodynamic measures. Category 1 failed to maintain detectable serum efalizumab or T cell CD11a down-modulation between doses. Category 2 achieved both. Category 3 achieved both and additionally maintained sustained T-cell CD11a saturation between doses. A dose-response relationship was also observed clinically and histologically. The mean decrease in the PASI score was 47% in category 3, 45% in category 2, and 10% in category 1 (<i>P</i>&lt;.001). Epidermal and dermal T-cell counts, epidermal thickness, and ICAM-1 and K16 expression decreased in categories 2 and 3 but not in category 1. Circulating lymphocyte counts increased in categories 2 and 3. <h3>Conclusions</h3> At doses of 0.3 mg/kg or more per week, intravenous efalizumab produced significant clinical and histologic improvement in psoriasis, which correlated with sustained serum efalizumab levels and T-cell CD11a saturation and down-modulation.

Psoriasis is characterized by epidermal hyperplasia, altered epidermal maturation, and local accumulation of acute and chronic inflammatory cells. Keratinocyte hyperplasia in psoriasis may be explained in part by overproduction of growth factors or cytokines which stimulate epidermal proliferation and by altered metabolism of growth-factor receptors in affected skin. Psoriatic epidermis displays overproduction of TGF-alpha and interleukin-6 (IL-6), factors produced by keratinocytes and other cell types in psoriatic skin. TGF-alpha and IL-6 are mitogens for normal human keratinocytes and act via specific receptors. The TGF-alpha receptor (EGF receptor) is overexpressed in psoriatic epithelium and its altered expression could be caused in part by gamma interferon which prevents normal receptor down-regulation in response to EGF binding. Several phenotypic features of the psoriatic keratinocyte, including growth activation and expression of HLA-DR, gamma-IP-10, ICAM-1, and other molecules, are best explained as resulting from the combined effects of TGF-alpha, IL-6, and gamma interferon (and possibly other cytokines) on epidermal keratinocytes. The multiple histologic features of psoriasis, including epidermal hyperplasia and accumulation of acute and chronic inflammatory cells, may be mediated by defined growth factors and cytokines that are produced in psoriatic skin and affect the function of diverse cell types.

The pathologic features of psoriatic plaques are inflammation and increased epidermal turnover. IP-10, a cytokine the expression of which is induced by gamma-interferon, is a member of a family of soluble mediators with inflammatory and growth-promoting activities. IP-10 protein was detected in keratinocytes and the dermal infiltrate from active psoriatic plaques using an affinity-purified rabbit anti-IP-10 antibody in immunoperoxidase studies. Successful treatment of active plaques decreased IP-10 expression in plaques. These results were corroborated by Northern blot analysis with an IP-10 cDNA probe. We have previously detected activated T cells and HLA-DR keratinocytes in active psoriatic plaques. Since IP-10 is detected in delayed cellular immune responses, the present study further points to the role of ongoing cellular immune responses in the pathogenesis of psoriasis.

Transforming growth factor alpha (TGF-alpha) is a 50-amino acid peptide, previously demonstrated only in transformed cell lines and human tumors, which is structurally homologous to epidermal growth factor (EGF). TGF-alpha expression in keratinocytes from normal individuals, patients with psoriasis, and patients with malignant skin diseases was investigated using an mAb raised against synthetic human TGF-alpha. mAb A1.5 reacted with TGF-alpha, but not EGF, in a sensitive ELISA. Keratinocytes in eight nodular basal cell carcinomas, one morpheic basal cell carcinoma, and one squamous cell carcinoma demonstrated intense membranous immunoperoxidase staining with mAb A1.5. Of even greater interest was the observation that the overlying normal epidermis, as well as the epidermis from five normal skin specimens, were stained by the mAb. Keratinocytes in plaques from 18 psoriasis patients were more intensely stained than those from normal skin. Cultured normal keratinocytes demonstrated membranous staining with mAb A1.5. Absorption of mAb A1.5 with synthetic human TGF-alpha completely removed the reactivity of mAb A1.5 with both basal cell tumors and normal epidermis. The demonstration of TGF-alpha in normal keratinocytes suggests that it plays a role in normal keratinocyte growth, wound healing, and in the pathogenesis of acanthosis.

The definitions of psoriasis severity and clinically significant improvement in psoriasis are used to classify treatments, obtain Food and Drug Administration approval, and determine product labeling and reimbursement. The Medical Advisory Board of the National Psoriasis Foundation has addressed these issues because of their importance in the clinical trials that are conducted to gain FDA approval of indications. Narrow indications, which are without a sound rational basis, will-in this era of constant oversight by third party payers-affect physicians' ability to manage patients with psoriasis. Body surface area (BSA) is usually used to define severity for clinical trials. It is not optimal for defining psoriasis severity because there are some patients with low BSA involvement who have very severe psoriasis and some patients with high BSA involvement who have mild psoriasis. We conclude that a quality of life (QOL) standard is better than BSA measurement for identifying patients with severe psoriasis. The second issue is what defines clinically significant improvement for patients with psoriasis. Setting an arbitrarily high criterion of clinical efficacy for new psoriasis treatments will likely limit the development and approval of useful treatments. To maximize the availability of useful psoriasis treatments, it is our thesis that psoriasis treatments should be approved when they have been shown to produce a statistically significant level of improvement in well-designed clinical trials.

We treated a 57-year-old woman for refractory inflammatory bowel disease with a humanized anti-tumor necrosis factor alpha monoclonal antibody (Infliximab). The patient also had a 15-year history of Crohn's disease and a 20-year history of moderate to severe psoriasis. She received a single infusion of Infliximab (5 mg/kg). Two weeks after the infusion her psoriasis had dramatically improved in appearance. To our knowledge, our case is the first reported instance of successful anti-tumor necrosis factor alpha therapy in psoriasis.

Efalizumab inhibits multiple T-cell-mediated processes.To evaluate 12- and 24-week efalizumab therapy for psoriasis.In this phase III, randomized, double-blind trial, 498 patients received subcutaneous 1 or 2 mg/kg/wk efalizumab or placebo for 12 weeks. Efalizumab-treated patients who achieved <75% Psoriasis Area and Severity Index improvement (PASI-75) were re-randomized to a second 12-week course of treatment. Results At week 12, 39% and 27% of efalizumab-treated patients (1 and 2 mg/kg, respectively) achieved PASI-75 (vs 2% placebo; P < .001, both dose groups). At week 24, an additional 20% of efalizumab-treated patients achieved PASI-75 (vs placebo 7%, P = .018). Efalizumab was well tolerated.Twelve-week efalizumab treatment resulted in significant improvement; extension of therapy to 24 weeks resulted in additional improvement in patients who initially had not achieved PASI-75. There were no significant changes in safety profile during weeks 13-24.

CD11a/CD18 comprise subunits of leukocyte function associated antigen (LFA-1), a T-cell surface molecule important in T-cell activation, T-cell emigration into skin, and cytotoxic T-cell function.We explored the immunobiologic and clinical effects of treating moderate to severe psoriasis vulgaris with a single dose of humanized monoclonal antibody against CD11a (hu1124).This was an open label study with a single dose of hu1124 at doses of 0.03 to 10 mg/kg. Clinical (Psoriasis Area and Severity Index [PASI]) and immunohistologic parameters (epidermal thickness, epidermal and dermal T-cell numbers, and keratinocyte intercellular adhesion molecule 1 [ICAM-1] expression) were followed.Treatment with hu1124, at doses higher than 1.0 mg/kg (group III), completely blocks CD11a staining for at least 14 days in both blood and psoriatic plaques. At 0.3 to 1.0 mg/kg, T-cell CD11a staining was completely blocked; however, blockade lasted less than 2 weeks (group II). Only partial saturation of either blood or plaque cellular CD11a was observed at doses of hu1124 between 0.01 and 0.1 mg/kg (group I). This pharmacodynamic response was accompanied by decreased numbers of epidermal and dermal CD3(+) T cells, decreased keratinocyte and blood vessel expression of ICAM-1, and epidermal thinning. Statistically significant drops in PASI compared with baseline were observed in group II patients at weeks 3 and 4 and in group III patients at weeks 2 through 10. No significant drop in PASI score was observed in group 1. Adverse events were mild at doses of 0.3 mg/kg or less and included mild chills, abdominal discomfort, headache, and fever. At a single dose of 0.6 mg/kg or higher, headache was the most common dose-limiting toxicity observed.Targeting CD11a may improve psoriasis by inhibiting T-cell activation, T-cell emigration into the skin, and cytotoxic T-cell function.

Psoriasis is a chronic and debilitating inflammatory disease associated with serious comorbidities. Psoriasis can have a significant impact on a patient's quality of life and is associated with loss of productivity, depression, and an increased prevalence of malignancy. Emerging comorbidities of psoriasis include cardiovascular disease and metabolic syndrome. Psoriasis patients have an increased prevalence of the core components of metabolic syndrome, including obesity, dyslipidemia, and insulin resistance. The relationship between psoriasis and comorbidities such as metabolic syndrome and cardiovascular disease is likely linked to the underlying chronic inflammatory nature of psoriasis. The molecular mechanisms involved in psoriasis‐associated dysregulation of metabolic function are believed to be due, in large part, to the action of increased levels of proinflammatory factors, such as tumor necrosis factor‐alpha, that are central to the pathogenesis of psoriasis. Recent studies investigating the effects of tumor necrosis factor antagonists on the treatment of cardiovascular disease and metabolic syndrome support this concept.

The prevalence of psoriasis in patients with Crohn's disease (CD) is higher than chance would allow if they were mutually exclusive diseases. A close examination reveals genetic and pathologic connections between these diseases. An appreciation for the role of tumor necrosis factor-alpha in both diseases has proven very important. Increased levels of this inflammatory cytokine have been measured in CD lesions, and in 1997 a clinical trial demonstrated the response of this disease to infliximab, a monoclonal antibody specific for tumor necrosis factor-alpha. A subsequent clinical trial evaluated infliximab in a patient with CD and psoriasis, another disease in which increased levels of tumor necrosis factor-alpha are seen in lesions. Scientists noticed the marked skin improvement of this patient and later demonstrated the efficacy of infliximab for psoriasis in a randomized, double-blind, placebo-controlled trial. Thus, an appreciation for connections between psoriasis and CD can suggest novel therapeutic strategies with ensuing benefits to patients. This article reviews epidemiologic, genetic, and pathologic connections between psoriasis and CD and discusses pharmaceuticals targeting inflammatory mediators common to each disease. (J Am Acad Dermatol 2003;48:805-21.)At the completion of this learning activity, participants should understand how psoriasis and Crohn's disease are related at epidemiologic, genetic, and pathological levels and should appreciate how to use this knowledge to treat these diseases.

Immunoperoxidase staining of skin sections and immunofluorescence analysis of keratinocyte suspensions obtained from suction blisters of psoriatic plaques were performed using an mAb, Josh 524.4.1, and Fab'2 fragments of a rabbit antiserum, both of which are directed against nonpolymorphic determinants of HLA-DR molecules. HLA-DR+ keratinocytes were present in plaques, but not normal-appearing skin, from a significant portion of patients with active psoriasis. Double-labelling immunofluorescence experiments with either the monoclonal or polyclonal anti-HLA-DR antibody, in conjunction with the mAb OKT6, which identifies DR+ Langerhans cells, demonstrated that HLA-DR molecules were present on OKT6- keratinocytes. The dermal infiltrate of psoriatic plaques contained T cells expressing the activation antigens, IL-2 receptor (Tac) and HLA-DR, as well as macrophages and OKT6+ cells. There was little difference in the characteristics of the dermal infiltrate between the lesions with or without HLA-DR+ keratinocytes. OKT6+ presumptive Langerhans cells were also found in the dermal infiltrates of patients with lichen planus, contact dermatitis, spongiotic dermatitis, erythema multiforme, basal and squamous cell carcinoma. Studies of keratinocyte suspensions showed that 7-84% of keratinocytes were HLA-DR+. Flow cytometry experiments showed that keratinocytes at all stages of differentiation were HLA-DR+. However, the stem cell-enriched population contained the highest proportion of HLA-DR+ cells. HLA-DR expression by keratinocytes correlated with disease activity. The expression was reversible with successful medical therapy. HLA-DR+ keratinocytes may activate T cells directly or may present an as yet unknown antigen to T cells. These studies provide further support for the hypothesis that immunological mechanisms play an important role in the pathogenesis of psoriasis.

Etanercept, a recombinant human tumor necrosis factor (TNF) receptor fusion protein, is FDA approved for psoriasis and psoriatic arthritis. TNFalpha increases the synthesis of proinflammatory cytokines and leads to the activation of multiple signaling pathways, including nuclear factor kappa B (NF-kappaB). The Rel/NF-kappaB transcription factors play a central role in numerous cellular processes, including the stress response and keratinocyte proliferation and differentiation. Utilizing a phosphorylation-specific antibody, we examined the expression of active nuclear NF-kappaB/RelA via immunohistochemistry in normal skin, non-lesional psoriatic skin, lesional psoriatic skin, and lesional skin from patients treated with etanercept. There was no expression of active nuclear NF-kappaB in the normal epidermis, whereas a basal level of constitutive active phosphorylated NF-kappaB/RelA was present in uninvolved epidermis from psoriasis patients. There was also significant upregulation of active phosphorylated NF-kappaB/RelA in the epidermis from psoriatic plaques. Serial biopsies from psoriasis patients treated with etanercept at 1, 3, and 6 mo demonstrated a significant downregulation of phosphorylated NF-kappaB/RelA, which correlated with decreases in epidermal thickness, restoration of normal markers of keratinocyte differentiation, and clinical outcomes. These data suggest that activation of NF-kappaB plays a significant role in the pathogenesis of psoriasis and that a potential mechanism of action for TNF-targeting agents is downregulation of NF-kappaB transcriptional activity.

Psoriasis is characterized by activation of T cells with a type 1 cytokine profile. IL-12 and IL-23 produced by APCs are essential for inducing Th1 effector cells. Promising clinical results of administration of an Ab specific for the p40 subunit of IL-12 and IL-23 (anti-IL-12p40) have been reported recently. This study evaluated histological changes and mRNA expression of relevant cytokines and chemokines in psoriatic skin lesions following a single administration of anti-IL-12p40, using immunohistochemistry and real-time RT-PCR. Expression levels of type 1 cytokine (IFN-gamma) and chemokines (IL-8, IFN-gamma-inducible protein-10, and MCP-1) were significantly reduced at 2 wk posttreatment. The rapid decrease of these expression levels preceded clinical response and histologic changes. Interestingly, the level of an anti-inflammatory cytokine, IL-10, was also significantly reduced. Significant reductions in TNF-alpha levels and infiltrating T cells were observed in high responders (improvement in clinical score, > or =75% at 16 wk), but not in low responders. Of importance, the levels of APC cytokines, IL-12p40 and IL-23p19, were significantly decreased in both responder populations, with larger decreases in high responders. In addition, baseline levels of TNF-alpha significantly correlated with the clinical improvement at 16 wk, suggesting that these levels may predict therapeutic responsiveness to anti-IL-12p40. Thus, in a human Th1-mediated disease, blockade of APC cytokines by anti-IL-12p40 down-regulates expression of type 1 cytokines and chemokines that are downstream of IL-12/IL-23, and also IL-12/IL-23 themselves, with a pattern indicative of coordinated deactivation of APCs and Th1 cells.

Psoriasis is a common chronic inflammatory disease that is associated with serious comorbidities, including psoriatic arthritis, reduced quality of life, depression, malignancy, and cardiovascular comorbidities. Patients with psoriasis have been shown to have an increased incidence of metabolic syndrome and cardiovascular disease compared with the general population. The chronic inflammatory nature of psoriasis has been suggested to be a contributing and potentially independent risk factor for the development of cardiovascular comorbidities. Understanding the interrelationship between these conditions is important for the management of psoriasis and the associated comorbidities. This review will focus on the range of comorbidities associated with psoriasis, with emphasis on cardiometabolic conditions and the aim of encouraging primary care physicians to screen psoriatic patients for cardiometabolic disorders and risk factors.

Psoriasis is characterized by alterations in both the epidermis and dermis of the skin. Epidermal keratinocytes display marked proliferative activation and differentiate along an "alternate" or "regenerative" pathway, while the dermis becomes infiltrated with leukocytes, particularly interleukin 2 (IL-2) receptor-bearing "activated" T cells. Psoralens, administered by the oral route, have therapeutic effects in psoriasis when photochemically activated by ultraviolet A light (PUVA therapy). Recently psoralen bath therapy has been introduced to more effectively deliver this agent to the diseased skin. We have correlated the efficacy of PUVA bath therapy with its effects on specific molecular and cellular parameters of disease, in 10 consecutive patients with recalcitrant psoriasis. Rapid clearing of lesions occurred in 8 out of 10 patients. Biopsies were taken from lesional and nonlesional skin before and after a single round of therapy, and observation was continued in our Clinical Research Center at The Rockefeller University. Enumeration of cycling keratinocytes with the Ki-67 monoclonal antibody showed that PUVA reduced cell proliferation by 73%. The pathological increase in insulin-like growth factor 1 (IGF-1) receptors was reversed, whereas epidermal growth factor (EGF) receptors, which are also increased in psoriasis, remained unchanged. Keratinocyte proteins that are expressed in abnormal sites of the epidermis during psoriasis, i.e., keratin 16, filaggrin, and involucrin, were, after PUVA treatment, localized to their normal sites. Epidermal and dermal T-lymphocytes (CD3+), as well as CD4+, CD8+, and IL-2 receptor+ subsets, were strongly suppressed by PUVA, with virtual elimination of IL-2 receptor+ T cells in some patients. Consistent with diminished lymphocyte activation, HLA-DR expression by epidermal keratinocytes was markedly reduced in treated skin. In comparison to cyclosporine treatment of psoriasis, PUVA therapy leads to more complete reversal of pathological epidermal and lymphocytic activation, changes which we propose to be the cellular basis for a more sustained remission of disease after PUVA treatment.

ABSTRACT Fifty-two healthy adult male and female volunteers were enrolled in this double-blind study to determine the maximum tolerated dose, characterize the pharmacokinetics, and obtain serum bactericidal activity (SBA) data for intravenous dalbavancin. Subjects were assigned to single- or multiple-dose groups and randomized to receive dalbavancin or placebo intravenously over 30 min. Doses started at 140 mg in the single-dose group and with a 300-mg loading dose (LD), followed by six daily 30-mg maintenance doses (MDs), in the multiple-dose cohort and escalated to a 1,120-mg single dose and a 1,000-mg LD and 100-mg MD regimen. Plasma, urine, and skin blister fluid aspirate drug concentrations were measured, and pharmacokinetic parameters were determined via noncompartmental methods. SBA against methicillin-resistant Staphylococcus aureus (MRSA) was determined at several time points. Adverse events and changes from the baseline for laboratory data, electrocardiograms, audiologic assessments, physical examinations, and vital signs were assessed. Concentrations increased in proportion to the dose. Steady-state concentrations were achieved by day 3 with the 10:1 LD-MD regimen. The half-life averaged 181 h, and the mean volume of distribution and clearance were 9.75 liters and 0.0473 liters/h, respectively. Mean values were similar in all groups and in males and females. The portion of the dose excreted renally averaged 33.5%. Bactericidal activity was demonstrated in serum at 7 days in all subjects receiving single doses of ≥500 mg. All doses were well tolerated. Dose-limiting toxicity was not encountered. No changes in auditory or vestibular function occurred. The long half-life and maintenance of SBA against MRSA for 1 week suggest that weekly dosing may be feasible.

Cyclosporine has been in worldwide use for 15 years for patients who have undergone transplantation operations and is now being used to control inflammatory reactions in other organs (eg, joints, bowel, and skin). Neoral, a more consistently absorbed form of cyclosporine, has recently been approved by the Food and Drug Administration for the treatment of psoriasis. This report outlines the indications, contraindications, dosage recommendations, monitoring requirements, adverse events, drug interactions, interactions with other psoriasis treatments, and suggestions for cyclosporine’s use in rotational therapy. (J Am Acad Dermatol 1998;39:464-75.)

As tumor necrosis factor (TNF)-alpha inhibitors gain wider use in clinical practice, it is becoming increasingly evident that these potent immunosuppressants can also induce inflammatory reactions. We present two cases of lichen planus-like eruptions after infliximab and adalimumab therapy for psoriasis, and review the literature on this phenomenon. Eleven cases of lichen planus or lichenoid drug eruptions have been previously reported in patients taking TNF-alpha inhibitors, in addition to several cases of psoriasiform eruptions with a lichenoid histology. Because TNF-alpha has been implicated in the pathogenesis of lichen planus, induction of lichenoid reactions by TNF-alpha inhibition is somewhat unexpected. We consider potential immunologic mechanisms, and suggest that TNF-alpha inhibition may precipitate lichenoid reactions through disruption of a delicate balance between TNF-alpha and interferon-alpha in susceptible patients.

A previous phase II trial demonstrated that the fully human anti-IL-12/23 mAb briakinumab was efficacious in moderate-to-severe psoriasis. A subsequent 52-week, double-blind, placebo-controlled phase III study evaluated induction and maintenance treatment. Patients were randomized 2:1 to briakinumab (200 mg at weeks 0 and 4 and 100 mg at week 8) or placebo; those with physician's global assessment "clear" or "minimal" (PGA "clear/minimal") at week 12 were then re-randomized 2:2:1 to briakinumab 100 mg every 4 weeks (q4-wk), every 12 weeks (q12-wk), or to matching placebo to week 52. Primary analyses conducted by nonresponder imputation compared proportions achieving PGA "clear/minimal" (weeks 12 and 52) and ≥75% improvement in psoriasis area and severity index (PASI 75; week 12). In all, 76.0% of briakinumab vs. 4.3% of placebo-treated patients achieved PGA "clear/minimal," and 80.7% vs. 4.5%, respectively, achieved PASI 75 at week 12 (P<0.001 each). At week 52, 79.2% of q4-wk-treated patients achieved PGA "clear/minimal" compared with 41.6% and 6.0% of q12-wk and placebo-treated patients, respectively (P<0.001 for all treatment comparisons). Higher numbers of the following adverse events (AEs) of interest were observed with briakinumab during the placebo-controlled period, suggesting the need for surveillance for these events: serious infections (five vs. one event with briakinumab vs. placebo, respectively), nonmelanoma skin cancers (NMSCs; four vs. zero squamous cell carcinomas (SCCs)), and major adverse cardiovascular events (MACEs; five vs. zero events).

Janus-associated kinases (JAKs) are involved in signal transduction from a variety of cytokines implicated in the pathogenesis of psoriasis, including interleukin (IL)-12, IL-23, and interferon-γ. INCB018424, a small molecule inhibitor of JAK1 and JAK2, inhibits cytokine-induced JAK/signal transducers and activators of transcription signaling and the resultant production of inflammatory proteins (eg, IL-17).We sought to demonstrate proof of concept in patients with stable plaque psoriasis.Patients were dosed with vehicle, 0.5% or 1.0% INCB018424 phosphate cream once a day or 1.5% twice a day for 28 days. Additional groups included two active comparators (calcipotriene 0.005% cream or betamethasone dipropionate 0.05% cream).Both the 1% and the 1.5% cream improved lesion thickness, erythema, and scaling and reduced lesion area compared with placebo. A composite lesion score decreased by greater than 50% with the efficacious doses of INCB018424 compared with 32% for vehicle controls. Topical application of INCB018424 was well tolerated with few mild adverse events noted. Mean plasma concentrations of INCB018424 after topical application of 0.5% to 1.5% cream were in the low nanomolar range, representing a fraction (<1%) of the half maximal inhibitory concentration (IC(50)) in whole blood for inhibition of cytokine-stimulated signal transducers and activators of transcription-3 phosphorylation.This study was limited by the relatively short study duration and small sample size.Topical INCB018424 is safe, is well tolerated, and exhibits clinical activity in the topical treatment of psoriasis.

<h3>Background</h3> Although etanercept is used as a continuous therapy for moderate to severe plaque psoriasis, intermittent use may be necessary in some instances. <h3>Objective</h3> In this randomized, open-label study, we evaluated the effectiveness and safety of continuous versus interrupted etanercept therapy. <h3>Methods</h3> All patients received uninterrupted etanercept 50 mg twice weekly during the first 12 weeks, followed by either continuous (n = 1272) or interrupted (n = 1274) etanercept 50 mg once weekly in the next 12 weeks. The primary effectiveness end point was the proportion of responders (those who achieved a Physician's Global Assessment [PGA] score ≤2 and improvement from baseline) at week 24. Secondary end points included the PGA "clear/almost clear" status, the PGA Scalp Psoriasis score, and the Dermatology Life Quality Index. A modified intent-to-treat analysis was performed. <h3>Results</h3> At week 12, comparable high proportions of responders were reported in the continuous (71.3%) and interrupted (72.0%) arms. However, the proportion of responders at week 24 was greater in the continuous group than in the interrupted group (71.0% vs 59.5%; <i>P</i> < .0001). Similar results were observed in secondary end points. The mean number of etanercept doses (1 dose=50 mg) received by patients in the continuous group was 33.4, compared with 28.0 in the interrupted group. Etanercept was well tolerated in both treatment arms. <h3>Limitations</h3> We examined one round of discontinuation and re-treatment; interrupted therapy provided less total medication to responding patients. <h3>Conclusions</h3> Continuous and interrupted etanercept therapy was effective and generally well tolerated in patients with psoriasis, with greater improvements observed in the continuous arm at week 24. Most patients regained their response after reinitiation of etanercept.

The Canadian Guidelines for the Management of Plaque Psoriasis were reviewed by the entire National Psoriasis Foundation Medical Board and updated to include newly approved agents such as ustekinumab and to reflect practice patterns in the United States, where the excimer laser is approved for psoriasis treatment. Management of psoriasis in special populations is discussed. In the updated guidelines, we include sections on children, pregnant patients or pregnant partners of patients, nursing mothers, the elderly, patients with hepatitis B or C virus infections, human immunodeficiency virus-infected patients, and patients with malignant neoplasms, as well as sections on tumor necrosis factor blockers, elective surgery, and vaccinations.

An urgent need exists in the United States to establish treatment goals in psoriasis.We aim to establish defined treatment targets toward which clinicians and patients with psoriasis can strive to inform treatment decisions, reduce disease burden, and improve outcomes in practice.The National Psoriasis Foundation conducted a consensus-building study among psoriasis experts using the Delphi method. The process consisted of: (1) literature review, (2) pre-Delphi question selection and input from general dermatologists and patients, and (3) 4 Delphi rounds.A total of 25 psoriasis experts participated in the Delphi process. The most preferred instrument was body surface area (BSA). The most preferred time for evaluating patient response after starting new therapies was at 3 months. The acceptable response at 3 months postinitiation was either BSA 3% or less or BSA improvement 75% or more from baseline. The target response at 3 months postinitiation was BSA 1% or less. During the maintenance period, evaluation every 6 months was most preferred. The target response at every 6 months maintenance evaluation is BSA 1% or less.Although BSA is feasible in practice, it does not encompass health-related quality of life, costs, and risks of side effects.With defined treatment targets, clinicians and patients can regularly evaluate treatment responses and perform benefit-risk assessments of therapeutic options individualized to the patient.

BackgroundExisting therapies for vitiligo are limited in efficacy and can be associated with undesirable side effects. Topical Janus kinase inhibitors may offer a new therapeutic option for vitiligo.ObjectiveWe sought to assess the role of topical ruxolitinib 1.5% cream, a Janus kinase inhibitor, in vitiligo treatment.MethodsThis 20-week, open-label, proof-of-concept trial of twice-daily topical ruxolitinib 1.5% cream was conducted in 12 patients with a minimum of 1% affected body surface area of vitiligo. The primary outcome was percent improvement in Vitiligo Area Scoring Index from baseline to week 20.ResultsOf 12 patients screened, 11 were enrolled and 9 completed the study (54.5% men; mean age, 52 years). Four patients with significant facial involvement at baseline had a 76% improvement in facial Vitiligo Area Scoring Index scores at week 20 (95% confidence interval, 53-99%; P = .001). A 23% improvement in overall Vitiligo Area Scoring Index scores was observed in all enrolled patients at week 20 (95% confidence interval, 4-43%; P = .02). Three of 8 patients responded on body surfaces and 1 of 8 patients responded on acral surfaces. Adverse events were minor, including erythema, hyperpigmentation, and transient acne.LimitationsLimitations of the study include the small sample size and open-label study design.ConclusionsTopical ruxolitinib 1.5% cream provided significant repigmentation in facial vitiligo and may offer a valuable new treatment for vitiligo. Existing therapies for vitiligo are limited in efficacy and can be associated with undesirable side effects. Topical Janus kinase inhibitors may offer a new therapeutic option for vitiligo. We sought to assess the role of topical ruxolitinib 1.5% cream, a Janus kinase inhibitor, in vitiligo treatment. This 20-week, open-label, proof-of-concept trial of twice-daily topical ruxolitinib 1.5% cream was conducted in 12 patients with a minimum of 1% affected body surface area of vitiligo. The primary outcome was percent improvement in Vitiligo Area Scoring Index from baseline to week 20. Of 12 patients screened, 11 were enrolled and 9 completed the study (54.5% men; mean age, 52 years). Four patients with significant facial involvement at baseline had a 76% improvement in facial Vitiligo Area Scoring Index scores at week 20 (95% confidence interval, 53-99%; P = .001). A 23% improvement in overall Vitiligo Area Scoring Index scores was observed in all enrolled patients at week 20 (95% confidence interval, 4-43%; P = .02). Three of 8 patients responded on body surfaces and 1 of 8 patients responded on acral surfaces. Adverse events were minor, including erythema, hyperpigmentation, and transient acne. Limitations of the study include the small sample size and open-label study design. Topical ruxolitinib 1.5% cream provided significant repigmentation in facial vitiligo and may offer a valuable new treatment for vitiligo.

Journal Article Successful treatment of moderate to severe plaque psoriasis with the PEGylated Fab′ certolizumab pegol: results of a phase II randomized, placebo‐controlled trial with a re‐treatment extension Get access K. Reich, K. Reich Dermatologikum Hamburg, Stephansplatz 5, 20354 Hamburg, GermanyGeorg‐August‐University, Göttingen, Germany Kristian Reich. E‐mail: kreich@dermatologikum.de Search for other works by this author on: Oxford Academic Google Scholar J.‐P. Ortonne, J.‐P. Ortonne Department of Dermatology, University of Nice‐Sophia Antipolis, Nice, France Search for other works by this author on: Oxford Academic Google Scholar A.B. Gottlieb, A.B. Gottlieb Tufts Medical Center, Boston, MA, U.S.A Search for other works by this author on: Oxford Academic Google Scholar I.J. Terpstra, I.J. Terpstra UCB Pharma, Brussels, Belgium Search for other works by this author on: Oxford Academic Google Scholar G. Coteur, G. Coteur UCB Pharma, Brussels, Belgium Search for other works by this author on: Oxford Academic Google Scholar C. Tasset, C. Tasset UCB Pharma, Brussels, Belgium Search for other works by this author on: Oxford Academic Google Scholar P. Mease P. Mease Swedish Medical Center and University of Washington, Seattle, WA, U.S.A Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 167, Issue 1, 1 July 2012, Pages 180–190, https://doi.org/10.1111/j.1365-2133.2012.10941.x Published: 01 July 2012 Article history Accepted: 06 March 2012 Published: 01 July 2012

To evaluate the efficacy of clazakizumab, a monoclonal antibody with high affinity and specificity for the interleukin-6 (IL-6) cytokine, in psoriatic arthritis (PsA).In this randomized, double-blind, placebo-controlled, dose-ranging study (ClinicalTrials. gov identifier: NCT01490450), patients with active PsA and an inadequate response to nonsteroidal antiinflammatory drugs were randomized (1:1:1:1) to receive subcutaneous placebo or clazakizumab 25 mg, 100 mg, or 200 mg every 4 weeks, with or without methotrexate. The primary end point was the response rate according to the American College of Rheumatology 20% criteria for improvement (ACR20) at week 16, with secondary efficacy end points at weeks 16 and 24.A total of 165 patients were randomized. At week 16, the ACR20 response rate was significantly higher with clazakizumab 100 mg versus placebo (52.4% versus 29.3%; P = 0.039). ACR20 response rates at week 16 were 46.3% with clazakizumab 25 mg (P = 0.101 versus placebo) and 39.0% with clazakizumab 200 mg (P = 0.178 versus placebo). ACR50/ACR70 response rates were numerically higher with clazakizumab versus placebo at weeks 16 and 24. Compared with placebo, clazakizumab treatment significantly improved musculoskeletal manifestations (joint signs and symptoms, enthesitis, and dactylitis), with minimal improvements in skin disease, without clear evidence of a dose response. Clazakizumab was well tolerated.This is the first clinical trial of an IL-6-targeted therapy in PsA. Clazakizumab may be an effective treatment option for musculoskeletal aspects of PsA, but because of the lack of a dose response in this study, further studies are required to confirm the appropriate dose. The safety profile is consistent with the pharmacology of IL-6 blockade and prior clinical experience with this antibody in rheumatoid arthritis.

Objective To evaluate ustekinumab efficacy and safety in psoriatic arthritis (PsA) patients with peripheral arthritis and physician-reported spondylitis (termed the ‘spondylitis subset’). Methods Adults with active PsA (PSUMMIT-1/PSUMMIT-2, n=615/312) were randomised to ustekinumab 45 mg, 90 mg or placebo at week 0/week 4/q12 week. At week 16, patients with &lt;5% improvement in tender and swollen joints entered blinded early escape. A subset of patients with physician-identified spondylitis was evaluated with spondylitis-specific assessments, including Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and Ankylosing Spondylitis Disease Activity Score employing C reactive protein (ASDAS-CRP), through week 24. Results 256/927 (27.6%) PSUMMIT-1/PSUMMIT-2 patients (placebo/ustekinumab, n=92/164) comprised the evaluable spondylitis subset. At week 24, in this analysis subset, significantly more patients achieved BASDAI20/50/70 responses (54.8%/29.3%/15.3% vs 32.9%/11.4%/0%; p≤0.002), improvement in BASDAI question 2 concerning axial pain (1.85 vs 0.24; p&lt;0.001) and mean per cent ASDAS-CRP improvements (27.8% vs 3.9%; p&lt;0.001) for ustekinumab versus placebo recipients, respectively. Comparable to the overall study population, significant improvements were also achieved in psoriasis, peripheral arthritis, enthesitis, dactylitis, physical function and peripheral joint radiographs in the spondylitis subset. Conclusions In this post-hoc analysis of PsA patients with baseline peripheral arthritis and physician-reported spondylitis, ustekinumab-treated patients demonstrated significant improvements in axial signs and symptoms through week 24. Trial registration number PSUMMIT-1 ( NCT01009086 , EudraCT 2009-012264-14) and PSUMMIT-2 ( NCT01077362 , EudraCT 2009-012265-60); post-study results.

BackgroundThere is no consensus on core outcome domains for hidradenitis suppurativa (HS). Heterogeneous outcome measure instruments in clinical trials likely leads to outcome‐reporting bias and limits the ability to synthesize evidence.

Background The anti‐interleukin‐12/23p40 monoclonal antibody briakinumab has been shown in a phase II study to be effective psoriasis treatment.

To assess long-term efficacy, safety and tolerability of secukinumab up to 104 weeks in patients with active PsA.Patients with PsA (n = 397) were randomized to s.c. secukinumab 300, 150 or 75 mg or placebo at baseline, weeks 1, 2, 3 and 4 and every 4 weeks thereafter. Placebo-treated patients were re-randomized to receive secukinumab 300 or 150 mg s.c. from week 16 (placebo non-responders) or week 24 (placebo responders). Exploratory endpoints at week 104 included 20, 50 and 70% improvement in ACR criteria (ACR20, 50, 70); 75 and 90% improvement in the Psoriasis Area Severity Index, 28-joint DAS with CRP, presence of dactylitis and enthesitis and other patient-reported outcomes. For binary variables, missing values were imputed; continuous variables were analysed by a mixed-effects model for repeated measures.A total of 86/100 (86%), 76/100 (76%) and 65/99 (66%) patients in the secukinumab 300, 150 and 75 mg groups, respectively, completed 104 weeks. At week 104, ACR20 response rates after multiple imputation in the 300, 150 and 75 mg groups were 69.4, 64.4 and 50.3%, respectively. Sustained clinical improvements were observed through week 104 with secukinumab across other clinically important domains of PsA. Responses were sustained through week 104 regardless of prior anti-TNF-α use. Over the entire treatment period the incidence, type and severity of adverse events were consistent with those reported previously.Secukinumab provided sustained improvements in signs and symptoms and multiple clinical domains in patients of active PsA through 2 years of therapy. Secukinumab was well tolerated, with a safety profile consistent with that reported previously.ClinicalTrials.gov (https://clinicaltrials.gov), NCT01752634.

Background Etanercept plus methotrexate combination therapy has not been adequately investigated in psoriasis. Objectives To evaluate etanercept plus methotrexate vs. etanercept monotherapy in patients with moderate to severe plaque psoriasis who had not failed prior methotrexate or tumour necrosis factor-inhibitor therapy. Methods Patients received etanercept 50 mg twice weekly for 12 weeks followed by 50 mg once weekly for 12 weeks and were randomized 1 : 1 to receive methotrexate (7·5–15 mg weekly) or placebo. The primary endpoint was the proportion of patients achieving ≥75% improvement in Psoriasis Area and Severity Index (PASI 75) at week 24. Results In total, 239 patients were enrolled in each arm. PASI 75 was significantly higher at week 24 for the combination therapy group compared with the monotherapy group (77·3% vs. 60·3%; P < 0·0001). Other PASI improvement scores at week 12 [PASI 75, 70·2% vs. 54·3% (P = 0·01); PASI 50, 92·4% vs. 83·8% (P = 0·01); and PASI 90, 34·0% vs. 23·1% (P = 0·03)] showed similar results as did week 24 PASI 50 (91·6% vs. 84·6%; P = 0·01) and PASI 90 (53·8% vs. 34·2%; P = 0·01). Significantly more patients receiving combination therapy than monotherapy had static Physician’s Global Assessment of clear/almost clear at week 12 (65·5% vs. 47·0%; P = 0·01) and week 24 (71·8% vs. 54·3%; P = 0·01). Adverse events (AEs) were reported in 74·9% and 59·8% of combination therapy and monotherapy groups, respectively; three serious AEs were reported in each arm. Conclusions Combination therapy with etanercept plus methotrexate had acceptable tolerability and increased efficacy compared with etanercept monotherapy in patients with moderate to severe psoriasis.

Psoriasis is a chronic, inflammatory skin disease and has significant associated morbidity and effect on quality of life. It is important to determine whether dietary interventions help reduce disease severity in patients with psoriatic diseases.To make evidence-based dietary recommendations for adults with psoriasis and/or psoriatic arthritis from the Medical Board of the National Psoriasis Foundation.We used literature from prior systematic reviews as well as additional primary literature from the MEDLINE database from January 1, 2014, to August 31, 2017, that evaluated the impact of diet on psoriasis. We included observational and interventional studies of patients with psoriasis or psoriatic arthritis. The quality of included studies was assessed using the Newcastle-Ottawa scale for observational studies and the Cochrane Risk of Bias Tool for interventional studies. We made evidence-based dietary recommendations, which were voted on by the National Psoriasis Foundation Medical Board.We identified 55 studies meeting the inclusion criteria for this review. These studies represent 77 557 unique participants of which 4534 have psoriasis. Based on the literature, we strongly recommend dietary weight reduction with a hypocaloric diet in overweight and obese patients with psoriasis. We weakly recommend a gluten-free diet only in patients who test positive for serologic markers of gluten sensitivity. Based on low-quality data, select foods, nutrients, and dietary patterns may affect psoriasis. For patients with psoriatic arthritis, we weakly recommend vitamin D supplementation and dietary weight reduction with a hypocaloric diet in overweight and obese patients. Dietary interventions should always be used in conjunction with standard medical therapies for psoriasis and psoriatic arthritis.Adults with psoriasis and/or psoriatic arthritis can supplement their standard medical therapies with dietary interventions to reduce disease severity. These dietary recommendations from the National Psoriasis Foundation Medical Board will help guide clinicians regarding the utility of dietary interventions in adults with psoriatic diseases.

Psoriasis is a chronic inflammatory disease involving multiple organ systems and affecting approximately 3.2% of the world's population. In this section of the guidelines of care for psoriasis, we will focus the discussion on ultraviolet (UV) light–based therapies, which include narrowband and broadband UVB, UVA in conjunction with photosensitizing agents, targeted UVB treatments such as with an excimer laser, and several other modalities and variations of these core phototherapies, including newer applications of pulsed dye lasers, intense pulse light, and light-emitting electrodes. We will provide an in-depth, evidence-based discussion of efficacy and safety for each treatment modality and provide recommendations and guidance for the use of these therapies alone or in conjunction with other topical and/or systemic psoriasis treatments. Psoriasis is a chronic inflammatory disease involving multiple organ systems and affecting approximately 3.2% of the world's population. In this section of the guidelines of care for psoriasis, we will focus the discussion on ultraviolet (UV) light–based therapies, which include narrowband and broadband UVB, UVA in conjunction with photosensitizing agents, targeted UVB treatments such as with an excimer laser, and several other modalities and variations of these core phototherapies, including newer applications of pulsed dye lasers, intense pulse light, and light-emitting electrodes. We will provide an in-depth, evidence-based discussion of efficacy and safety for each treatment modality and provide recommendations and guidance for the use of these therapies alone or in conjunction with other topical and/or systemic psoriasis treatments. The American Academy of Dermatology (AAD) strives to produce clinical guidelines that reflect the best available evidence supplemented with the judgment of expert clinicians. Significant efforts are taken to minimize the potential for conflicts of interest to influence guideline content. The management of conflict of interest for this guideline complies with the Council of Medical Specialty Societies' Code of Interactions with Companies. Funding of guideline production by medical or pharmaceutical entities is prohibited, full disclosure is obtained and evaluated for all guideline contributors throughout the guideline development process, and recusal is used to manage identified relationships. The AAD conflict of interest policy summary may be viewed at www.aad.org. The authors' disclosed relationship with industry during guideline development appear at the end of this guideline. In accordance with AAD policy, a minimum 51% of workgroup members did not have any relevant conflicts of interest. Participation in 1 or more of the following activities constitutes a relevant conflict:•Service as a member of a speaker bureau, consultant, or advisory board member for pharmaceutical companies on the psoriasis disease state or psoriasis drugs in development or US Food and Drug Administration–approved.•Sponsored research funding or investigator-initiated studies with partial/full funding from pharmaceutical companies on the psoriasis disease state or psoriasis drugs in development or US Food and Drug Administration–approved. If a potential conflict was noted, the workgroup member recused himself or herself from discussion and drafting of recommendations pertinent to the topic area of interest. Complete group consensus was obtained for draft recommendations. Areas in which complete consensus was not achieved are shown transparently in the guideline. Authors (listed alphabetically) with relevant conflicts with respect to this guideline are noted with an asterisk*. April W. Armstrong,* MD, MPH, served as an investigator for AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Dermira, Eli Lilly and Company, Janssen-Ortho Inc, Leo Pharma Inc, National Institutes of Health, Novartis, Regeneron, and UCB, receiving grants and/or research funding; as an investigator for Regeneron and Sanofi, receiving no compensation; as an advisory board member for AbbVie, Amgen, Janssen-Ortho Inc, Merck & Co, Inc, Novartis, Pfizer, Inc, and UCB, receiving honoraria; as a consultant for AbbVie, Bristol-Myers Squibb, Celgene, Dermavant, Eli Lilly and Company, Genentech, Sanofi Genzyme, GlaxoSmithKline, Janssen-Ortho Inc, Janssen Pharmaceuticals, Inc, Leo Pharma, Inc, Menlo Therapeutics, Modernizing Medicine, Novartis Pharmaceuticals Corp, Ortho Dermatologics, Pfizer, Inc, Regeneron, Science 37, Inc, and Valeant, receiving honoraria; as a speaker for AbbVie, Eli Lilly and Company, Janssen Pharmaceuticals, Inc, Regeneron Pharmaceuticals, Inc, and Sanofi, receiving honoraria; and as a data safety member for Boehringer Ingelheim, and Merck & Co, Inc, receiving honoraria. Cody Connor, MD, has no relationships to disclose. Kelly M. Cordoro,* MD, served as a consultant for Valeant, receiving honoraria; as a consultant for Pfizer, Inc, receiving fees; as an advisory board member for Anacor Pharmaceuticals, Inc, receiving honoraria; and in another position as a member of the scientific steering committee for Celgene, receiving fees. Dawn M.R. Davis, MD, served as an investigator for Regeneron, receiving no compensation. Boni E. Elewski,* MD, served as a consultant for Boehringer Ingelheim, Celgene Corporation, Leo Pharma, Lilly ICOS LLC, Menlo Therapeutics, Novan (receiving no fees), Novartis Pharmaceuticals Corp, Pfizer, Inc, Sun Pharmaceutical Industries, Ltd, Valeant Pharmaceuticals International, and Verrica Pharmaceuticals, receiving honoraria; as a principal investigator for AbbVie, Amgen, AnaptysBio, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene Corporation, Eli Lilly and Company, Incyte Corporation, InflaRX GmbH, Janssen-Ortho Inc, LEO Pharma, Menlo Therapeutics, Merck & Co, Inc, Novartis Pharmaceuticals Corp, Pfizer, Inc, Regeneron, Sun Pharmaceuticals,Ltd, Valeant Pharmaceuticals International, Vanda Pharmaceuticals, and Vioment, receiving grants/research funding; as an advisory board member for Foundation for Research & Education of Dermatology, LEO Pharma, and Verrica Pharmaceuticals, Inc, receiving honoraria; and in another role for Hoffman-La Roche Ltd, receiving fees. Craig A. Elmets, MD, served as a consultant for Ferndale Laboratories, Inc, receiving honoraria; as a consultant/advisory board member for Vertex Pharmaceuticals, receiving fees and/or honoraria; as a principal investigator for the California Association of Winegrape Growers, receiving grants and/or research funding; as an investigator for Elorac,Inc, Idera Pharmaceuticals,Inc, Kyowa Hakko USA, and Solgenix LLC, receiving grants/research funding; as a data safety monitoring board member for Astellas Pharma US, Inc, and LEO Laboratories Ltd, receiving fees; as a stockholder for Medgenics, Inc, receiving no fees; and as a stockholder for Aevi Genomic Medicine (receiving stock) and Immunogen (paid to spouse). Joel M. Gelfand,* MD, MSCE, served as a consultant for AbbVie, BMS, Boehringer Ingelheim, Dermira, Dr Reddy, GlaxoSmithKline, Janssen Pharmaceuticals, Inc, Menlo Therapeutics, Novartis Pharmaceuticals Corp, Pfizer, Inc, Regeneron, Sanofi US Services, UCB (DSMB), and Valeant Pharmaceuticals North America LLC, receiving honoraria; as a consultant for BMS, receiving fees; as a speaker and/or faculty educator for CME supported by Eli Lilly and Company, receiving fees; as a principal investigator for AbbVie, Boehringer Ingelheim, Celgene, Eli Lilly and Company, Janssen Pharmaceuticals, Inc, Novartis Pharmaceuticals Corp, Ortho Dermatologics, Pfizer, Inc, Regeneron, and Sanofi/Sanofi US Services, receiving grants/research funding; as an investigator for Sanofi, receiving grants and/or research funding; as an advisory board member for Sanofi US Services, receiving honoraria; as a data safety monitoring board member for Coherus Biosciences and Merck & Co, Inc, receiving honoraria. In addition, Dr Gelfand has received payment for CME work related to psoriasis that was supported indirectly by Lilly and Company, Ortho Dermatologics, and Novartis; served in another role for Elsevier, Inc, receiving no compensation; served in another role for Eli Lilly and Company and UCB, receiving fees; and served in another role for Resiquimod, receiving patent royalties or other compensation for intellectual rights. Kenneth B. Gordon,* MD, served as a consultant for AbbVie, Almirall, Amgen, Boehringer Ingelheim, Bristol-Myers Squibb, Demira, Dermavant Sciences, Kyowa Hakko Kirin Pharma, Inc, Leo Pharma, Ortho Dermatologics, Sun Pharmaceuticals Ltd, and UCB, receiving honoraria; as a consultant for Genzyme, receiving fees; as a principal investigator for AbbVie, Amgen, Boehringer Ingelheim, Celgene Corporation, Eli Lilly and Company, Janssen Pharmaceuticals, Inc, Merck & Co, Inc, and Novartis Pharmaceuticals Corp, receiving grants and/or research funding; and as an advisory board member for Celgene Corporation, Janssen Pharmaceuticals Inc, Lilly ICOS LLC, Novartis Pharmaceuticals Corp, and Pfizer, Inc, receiving honoraria. Alice B. Gottlieb,* MD, PhD, served as a consultant for Abbott Laboratories, AbbVie, Akros Pharma, Inc, Allergan, Amgen, Amicus Therapeutics, Baxalta Incorporated, Bristol-Myers Squibb, Canfite, Celgene Corporation, CSL Behring, Dermira, Dr Reddy, DUSA Pharmaceuticals, Inc, GlaxoSmithKline, Incyte Corporation, KPI Therapeutics, Lilly ICOS LLC, Meiji Seika Pharma Co, Ltd, Merck & Co, Inc, Mitsubishi Pharma, Novartis Pharmaceuticals Corp, Sanofi-Aventis, Sienna Biopharmaceuticals, Sun Pharmaceutical Industries, Takeda Pharmaceuticals USA, Inc, Teva, UCB, Valeant Pharmaceuticals International, Valeant Pharmaceuticals North America LLC, XBiotech, and Xenoport, Inc, receiving honoraria; as a consultant for Aclaris Therapeutics, Inc, Avotres Inc, Merck & Co Inc, and XBiotech, receiving no compensation; as a speaker for AbbVie, Eli Lilly and Company, and Janssen Biotech, receiving honoraria; as a principal investigator for Abbott Laboratories, AbbVie, Allergan, Amgen, Celgene Corporation, Coronado Biosciences, Immune Control, Incyte Corporation, Janssen-Ortho Inc, LEO Pharma, Lerner Medical Devices,Inc, Lilly ICOS LLC, Merck & Co, Inc, Novartis Pharmaceuticals Corp, Novo Nordisk A/S, Pfizer Inc, UCB, Xbiotech, and Xenoport,Inc, receiving grants/research funding; as a principal investigator for Janssen-Ortho Inc, receiving honoraria; as an advisory board member for Abbott Laboratories, Actelion, Allergan, Amgen, Astellas Pharma US, Inc, Beiersdorf, Inc, BMS, Celgene Corporation, Coronado Biosciences, Dermira, Dr Reddy, Genentech, Janssen-Ortho Inc, Janssen Biotech, Leo Pharma US, Lilly ICOS LLC, Novartis Pharmaceuticals Corp, Novo Nordisk A/S, Pfizer, Inc, UCB, and Valeant, receiving honoraria; in another role for Amgen, receiving grants and/or research funding; in another role for Crescendo Bioscience and Karyopharm Therapeutics, receiving no compensation; in another role (data safety) for Catabasis Pharmaceuticals, Inc, receiving honoraria; and in another role for DermiPsor, receiving honoraria. Daniel H. Kaplan, MD, PhD, served as a consultant for Eli Lilly and Company, receiving no compensation and as a member of the data safety monitoring board for Hapten Sciences, receiving fees. Arthur Kavanaugh,* MD, served as a principal investigator for AbbVie, Amgen, BMS, Celgene Corporation, Eli Lilly and Company, Janssen Biotech, Novartis, Pfizer, Inc, and UCB, receiving grants/research funding. Matthew Kiselica, BA/BS, has no relationships to disclose. Dario Kivelevitch, MD, has a first-degree relative employed by Boehringer Ingelheim. Neil J. Korman,* MD, PhD, served as a consultant for Novartis Pharmaceuticals Corp, receiving honoraria; as a consultant for Dr Reddy's Laboratory, receiving fees; as a speaker for AbbVie, Celgene, Eli Lilly and Company, Genentech, Janssen, Novartis, Regeneron, and Sanofi, receiving honoraria; as a principal investigator for AbbVie, Amgen, Celgene Corporation, Chugai, Dermira, Eli Lilly and Company, Kyowa Hakko Kirin Pharma, Inc, LEO Pharma, Menlo Therapeutics, Merck, Pfizer, Prothena, Regeneron, Rhizen,Inc, Syntimmune, Trevi, and UCB, receiving grants and/or research funding; as an advisory board member for Amgen, Celgene Corporation, Eli Lilly and Company, Genentech, GlaxoSmithKline, Janssen Pharmaceuticals, Inc, Novartis Pharmaceuticals Corp, Pfizer, Inc, and Principia Biopharma, receiving honoraria; as an advisory board member for Dr Reddy's Laboratory, Immune Pharmaceuticals, Regeneron, Sanofi, Sun Pharma, and Valeant, receiving fees; as an advisory board member/consultant for AbbVie, Eli Lilly and Company, GlaxoSmithKline, Pfizer Inc, and Principa, receiving honoraria/fees; and in another role for Janssen Pharmaceuticals, Inc, receiving grants and/or research funding. Daniela Kroshinsky, MD, MPH, has no relationships to disclose. Mark Lebwohl,* MD, served as a consultant for Allergan, Almirall, Arcutis, Inc, Boehringer Ingelheim, Bristol-Myers Squibb, Castle Biosciences, Inc, Leo Pharma, Menlo Therapeutics, Mitsubishi Pharma, Neuroderm LTD, Pfizer, Inc, Promius/Dr Reddy, Theravance Biopharma, and Verrica Pharmaceuticals, Inc, receiving honoraria; as a principal investigator or investigator for AbbVie, Amgen, Inc, AstraZeneca, Boehringer Ingelheim, Celgene Corporation, Eli Lilly and Company, Incyte Corporation, Janssen Research and Development LLC/Johnson & Johnson, Leo Pharma, Medimmune, Novartis Pharmaceuticals Corp, Ortho-Dermatologics, Pfizer, Inc, SCIDerm, UCB, and ViDac Pharma receiving grants and/or research funding; and in another role for Corrona, Inc, Facilitation of International Dermatology Education, and the Foundation for Research and Education in Dermatology, receiving honoraria. Craig L. Leonardi,* MD, served as a consultant/advisory board member for AbbVie, Amgen, Boehringer Ingelheim, Celgene Dermira, Eli Lilly and Company, Janssen Pharmaceuticals, Inc, Leo Pharma A/S, Ortho Dermatologics, Pfizer, Inc, Sandoz (a Novartis Company), UCB, and Vitae, receiving honoraria; as a speaker for AbbVie, Amgen, Celgene Corporation, Eli Lilly and Company, Novartis, Sun Pharmaceuticals, Ltd, and UCB, receiving honoraria; and as a principal investigator for Actavis, Amgen, Boehringer Ingelheim, Celgene Corporation, Cellceutix, Coherus Biosciences, Corrona, Dermira, Eli Lilly and Company, Galderma Laboratories, LP, Glenmark Generics, Inc, Janssen Pharmaceuticals, Inc, Leo Pharma, Inc, Merck, Novartis, Novella, Pfizer, Inc, Sandoz (a Novartis Company), Sienna Biopharmaceuticals, Stiefel a GsK company, UCB, and Warner Chillcott, receiving other financial benefits (fee for service). Jason Lichten, MD, has no relationships to disclose. Henry W. Lim, MD, served as a principal or coinvestigator for Estee Lauder, Ferndale Laboratories,Inc, Incyte, and Unigen, receiving grants and/or research funding; and as a speaker and/or faculty education for Pierre Fabre Dermatologie, receiving honoraria. Nehal N. Mehta,* MD, MSCE, is a full-time US government employee and has served as a consultant for Amgen, Eli Lilly and Company, and Leo Pharma, receiving grants/other payments; as principal investigator and/or investigator for AbbVie, Celgene, Janssen Pharmaceuticals, Inc, and Novartis, receiving grants and/or research funding; and as a principal investigator for the National Institute of Health, receiving grants and/or research funding. Alan Menter,* MD, served as a consultant for Abbott Labs, AbbVie, Amgen, Eli Lilly and Company, Galderma USA, Janssen Pharmaceuticals Inc, LEO Pharma US, Menlo Therapeutics, Novartis, Sienna Biopharmaceuticals, and Wyeth Labs, receiving honoraria; as a consultant for New Enterprise Associates, Promius Pharma LLC, Spherix Global Insights US, UCB, and Valeant Pharmaceuticals North America, receiving fees; as a consultant for Afecta Pharmaceuticals, receiving no compensation; as a speaker for Abbott Labs, AbbVie, Amgen, Janssen Biotech, LEO Pharma, US, Pfizer, Inc, Promius Pharma LLC, Sienna Pharmaceuticals, UCB, and Wyeth Labs, receiving honoraria; as a principal investigator for AbbVie, Amgen, Boehringer Ingelheim, Celgene Corporation, Eli Lilly and Company, Janssen Pharmaceuticals, Inc, Medimetriks Pharmaceuticals,Inc, Merck & Co, Inc, Novartis Pharmaceutical Corp, and Pfizer, Inc, receiving grant and/or research funding; as an investigator for Eli Lilly and Company, and UCB, receiving honoraria; as an investigator for Abbott Labs, Leo Pharma US, and Sienna Biopharmaceuticals, receiving grants; as an advisory board member for Abbott Labs, AbbVie, Boehringer Ingelheim, Eli Lilly and Company, Janssen Pharmaceuticals, Inc, LEO Pharma US, Medscape, Pfizer, Inc, and Sienna Biopharmaceuticals, receiving honoraria; as an advisory board member for Amgen, receiving grant and/or research funding; as an advisory board member for Afecta Pharmaceuticals, receiving no compensation; and as an independent contractor for Prime Education, receiving fees. Amy S. Paller,* MD, served as a consultant for Amgen, Amicus Therapeutics, Anacor Pharmaceuticals, Inc, Aqua Pharmaceuticals, Boehringer Ingelheim International GmbH, BridgeBio Pharma, Castle Creek Pharma, Celgene Corporation, Dermavant Sciences, Dermira, Eli Lilly and Company, Galderma Laboratories, LP, Leo Pharma Inc, Genentech, Menlo Therapeutics, MorphoSys AG, Novartis Pharmaceuticals Corp, Pfizer Inc, Pierre Fabre Dermatologie, Proctor and Gamble, Regeneron, Sanofi, Scioderm, Shire, Sol-Gel Technologies, Stiefel a GSK company, Theravance Biopharma, UCB, Union Therapeuthic, Valeant Pharmaceuticals North America LLC, Vitae Pharmaceuticals, and Verrica, receiving honoraria; as a speaker/educator for Expanscience, receiving honoraria; as a principal investigator for AbbVie, Amgen, Anacor Pharmaceuticals, Inc, AnaptysBio, Celgene Corporation, Eli Lilly and Company, Galderma, Janssen Pharmaceuticals, Inc, Leo Pharma, Regeneron, and Scioderm, receiving no compensation. Sylvia L. Parra, MD, has no relationships to disclose. Arun L. Pathy, MD, has no relationships to disclose. Elizabeth A. Farley Prater, MD, has no relationships to disclose. Reena N. Rupani, MD, served as speaker for Nutrafol, receiving honoraria. Michael Siegel, PhD has no relationships to disclose. Benjamin Stoff, MD, MA, served as an investigator for Celtaxsys, Inc, receiving fees. Bruce E. Strober,* MD, PhD, served as a consultant for AbbVie, Almirall, Amgen, Boehringer Ingelheim, Celgene Corporation, Dermira, Eli Lilly and Company, GlaxoSmithKline, Janssen-Ortho Inc, Leo Pharma, Inc, Maruho Co, Ltd, Medac Pharma, Inc, Menlo Therapeutics, Novartis Pharmaceuticals Corp, Ortho Dermatologics, Pfizer, Inc, Sanofi-Regeneron, Sun Pharmaceuticals Industries, and UCB, receiving honoraria; as a consultant for Affibody, Arena, Bristol-Myers Squibb, Dermavant, Meiji Seika Pharma Co, Ltd, Sebela Pharmaceuticals, Sirtris, and UCB, receiving fees; as a principal investigator for AbbVie, Boehringer Ingelheim, Celgene Corporation, Eli Lilly and Company, Galderma, Janssen-Ortho Inc, Merck & Co, Pfizer, Inc, Sienna, and Sun Pharmaceutical Industries, receiving no compensation; as an advisory board member for AbbVie, Amgen, Bristol-Myers Squibb, Celgene Corporation, Dermira, Eli Lilly and Company, Janssen-Ortho Inc, Novartis Pharmaceuticals Corp, Pfizer, Inc, Sanofi-Regeneron, Sun Pharmaceuticals Industries, and UCB, receiving honoraria; as consultant/advisory board for AstraZeneca Pharmaceuticals LP, receiving fees/honoraria; and in another role for AbbVie and Janssen-Ortho Inc, receiving no compensation. Emily B. Wong, MD, has no relationships to disclose. Jashin J. Wu,* MD, served as a consultant for Abbvie, Allergan, Almirall, Amgen, Bristol-Myers Squibb, Celgene, Dermira, Dr Reddy's Laboratories, Eli Lilly and Company, Janssen Biotech, LEO Pharma, Novartis, Ortho Dermatologics, Pfizer, Inc, Promius Pharma, Regeneron, Sun Pharmaceutical Industries, Ltd, UCB, and Valeant Pharmaceuticals North America, LLC, receiving fees and/or honoraria; as a speaker for Abbvie, Celgene, Novartis, Regeneron, Sanofi Genzyme, Sun Pharmaceutical Industries Ltd, UCB, and Valeant Pharmaceuticals North America LLC, receiving honoraria; and as a principal/investigator for AbbVie, Amgen, AstraZeneca, Boehringer Ingelheim, Coherus Biosciences, Dermira, Eli Lilly and Company, Janssen Pharmaceuticals, Inc, Merck & Co, Inc, Novartis, Pfizer, Inc, Regeneron, Sandoz (a Novartis Company), and Sun Pharmaceutical Industries Ltd, receiving research and/or grant funding. Vidhya Hariharan, PhD, has no relationships to disclose. Adherence to these guidelines will not ensure successful treatment in every situation. Furthermore, these guidelines should not be interpreted as setting a standard of care, nor should they be deemed either inclusive of all proper methods of care or exclusive of other methods of care reasonably directed toward obtaining the same results. The ultimate judgment regarding the propriety of any specific therapy must be made by the physician and the patient in light of all the circumstances presented by the individual patient and the known variability and biologic behavior of the disease. Furthermore, the treatment dosages used in clinical trials may not be effective in certain cases, and some patients may require shorter intervals between doses and/or higher treatment doses of a particular treatment methodology. This guideline reflects the best available data at the time the guideline was prepared. The results of future studies will likely require revisions to the recommendations in this guideline to reflect new data. Although many patients with psoriasis may be capable of adequately controlling their disease with the use of topical treatments alone, often these interventions are insufficient and disease severity dictates the need for alternative options. While systemic and biologic treatments are heavily relied on for severe and widespread skin disease, these medications do come with risks of systemic side effects and immunosuppression that many patients may not be willing or able to assume. Phototherapy serves as a reasonable and effective treatment option for patients requiring more than topical medications and/or those wishing to avoid systemic medications or simply seeking an adjunct to a failing regimen. See Appendix 1 for definitions. This section covers the use of phototherapy in the treatment of psoriasis in adults; psoriasis treatment in the pediatric population is addressed in the Joint American Academy of Dermatology–National Psoriasis Foundation Guidelines of Care for the Management and Treatment of Psoriasis in Pediatric Population (in preparation). An evidence-based model was used, and evidence was obtained by using a search of the PubMed and MEDLINE databases from January 1, 2008, to December 31, 2017, for all newly identified clinical questions (Table I). Searches were limited to publications in the English language. Medical Subject Heading (MeSH) terms used alone or in various combinations in the search included psoriasis (plaque, vulgaris, guttate, erythrodermic, inverse, pustular), phototherapy, ultraviolet (short-wave, long-wave), targeted phototherapy (excimer laser), narrowband ultraviolet B (NB-UVB), photochemotherapy, psolaren ultraviolet A, broadband ultraviolet B (BB-UVB), grenz ray, climatotherapy, photodynamic therapy, visible light (red/blue), TURBO-UVB, intense pulsed light, and Goeckerman therapy.Table IClinical questionWhat are the efficacy, effectiveness, and adverse effects of the following phototherapy/photochemotherapy modalities used as monotherapy or in combination with other psoriasis therapies to treat psoriasis in adults?1)Narrowband ultraviolet B (NB-UVB)2)Broadband ultraviolet B (BB-UVB)3) Targeted phototherapy (excimer laser and excimer lamp)4)Psoralen plus ultraviolet A (PUVA) therapya.Topicalb.Bathc.Oral5)Photodynamic therapy6)Grenz ray therapy7)Climatotherapy8)Visible light therapy9)Goeckerman therapy10)Pulsed dye laser and Intense pulsed light Open table in a new tab For detailed methodology, see Appendix I. NB-UVB refers to wavelengths ranging from 311 to 313 nm, which are widely used for the treatment of generalized plaque psoriasis.1Almutawa F. Alnomair N. Wang Y. Hamzavi I. Lim H.W. Systematic review of UV-based therapy for psoriasis.Am J Clin Dermatol. 2013; 14: 87-109Crossref PubMed Scopus (55) Google Scholar, 2Archier E. Devaux S. Castela E. et al.Efficacy of psoralen UV-A therapy vs. narrowband UV-B therapy in chronic plaque psoriasis: a systematic literature review.J Eur Acad Dermatol Venereol. 2012; 26: 11-21Crossref PubMed Scopus (48) Google Scholar, 3Dayal S. Mayanka Jain V.K. Comparative evaluation of NBUVB phototherapy and PUVA photochemotherapy in chronic plaque psoriasis.Indian J Dermatol Venereol Leprol. 2010; 76: 533-537Crossref PubMed Scopus (9) Google Scholar, 4El-Mofty M. Mostafa W.Z. Bosseila M. et al.A large scale analytical study on efficacy of different photo(chemo)therapeutic modalities in the treatment of psoriasis, vitiligo and mycosis fungoides.Dermatol Ther. 2010; 23: 428-434Crossref PubMed Scopus (17) Google Scholar As outlined in Table II,5Mehta N.N. Shin D.B. Joshi A.A. et al.Effect of 2 psoriasis treatments on vascular inflammation and novel inflammatory cardiovascular biomarkers: a randomized placebo-controlled trial.Circ Cardiovasc Imaging. 2018; 11: e007394Crossref PubMed Scopus (41) Google Scholar, 6Ward W.H. Lambreton F. Goel N. Yu J.Q. Farma J.M. Clinical presentation and staging of melanoma.in: Ward W.H. Farma J.M. Cutaneous Melanoma: Etiology and Therapy. Codon Publications, Brisbane, Australia2017Crossref Google Scholar, 7Zanolli M. Feldman S.R. Phototherapy Treatment Protocols for Psoriasis and Other Photoherapy Responsive Dermatoses.2nd ed. Taylor & Francis, Milton, Abingdon, UK2005Google Scholar, 8Boztepe G. Karaduman A. Sahin S. Hayran M. Kolemen F. The effect of maintenance narrow-band ultraviolet B therapy on the duration of remission for psoriasis: a prospective randomized clinical trial.Int J Dermatol. 2006; 45: 245-250Crossref PubMed Scopus (23) Google Scholar, 9Menter A. Korman N.J. Elmets C.A. et al.Guidelines of care for the management of psoriasis and psoriatic arthritis: section 5. Guidelines of care for the treatment of psoriasis with phototherapy and photochemotherapy.J Am Acad Dermatol. 2010; 62: 114-135Abstract Full Text Full Text PDF PubMed Scopus (247) Google Scholar the starting dose for NB-UVB therapy can be based on skin phototype or minimal erythema dose (MED).2Archier E. Devaux S. Castela E. et al.Efficacy of psoralen UV-A therapy vs. narrowband UV-B therapy in chronic plaque psoriasis: a systematic literature review.J Eur Acad Dermatol Venereol. 2012; 26: 11-21Crossref PubMed Scopus (48) Google Scholar, 9Menter A. Korman N.J. Elmets C.A. et al.Guidelines of care for the management of psoriasis and psoriatic arthritis: section 5. Guidelines of care for the treatment of psoriasis with phototherapy and photochemotherapy.J Am Acad Dermatol. 2010; 62: 114-135Abstract Full Text Full Text PDF PubMed Scopus (247) Google Scholar, 10Parlak N. Kundakci N. Parlak A. Akay B.N. Narrowband ultraviolet B phototherapy starting and incremental dose in patients with psoriasis: comparison of percentage dose and fixed dose protocols.Photodermatol Photoimmunol Photomed. 2015; 31: 90-97Crossref PubMed Scopus (8) Google Scholar, 11Dawe R.S. Cameron H.M. Yule S. Ibbotson S.H. Moseley H.H. Ferguson J. A randomized comparison of methods of selecting narrowband UV-B starting dose to treat chronic psoriasis.Arch Dermatol. 2011; 147: 168-174Crossref PubMed Scopus (12) Google Scholar A frequency of twice or thrice weekly is effective and is therefore recommended.1Almutawa F. Alnomair N. Wang Y. Hamzavi I. Lim H.W. Systematic review of UV-based therapy for psoriasis.Am J Clin Dermatol. 2013; 14: 87-109Crossref PubMed Scopus (55) Google Scholar, 12Cameron H. Dawe R.S. Yule S. Murphy J. Ibbotson S.H. Ferguson J. A randomized, observer-blinded trial of twice vs. three times weekly narrowband ultraviolet B phototherapy for chronic plaque psoriasis.Br J Dermatol. 2002; 147: 973-978Crossref PubMed Scopus (0) Google Scholar, 13Dawe R.S. Wainwright N.J. Cameron H. Ferguson J. Narrow-band (TL-01) ultraviolet B phototherapy for chronic plaque psoriasis: three times or five times weekly treatment?.Br J Dermatol. 1998; 138: 833-839Crossref PubMed Scopus (83) Google Scholar A frequency greater than thrice weekly results in little added benefit, while at the same time exposing the patient to a higher total dose of UVB radiation and greater risk of ultraviolet (UV)-induced erythema.13Dawe R.S. Wainwright N.J. Cameron H. Ferguson J. Narrow-band (TL-01) ultraviolet B phototherapy for chronic plaque psoriasis: three times or five times weekly treatment?.Br J Dermatol. 1998; 138: 833-839Crossref PubMed Scopus (83) Google Scholar Although both twice-weekly treatment and thrice-weekly treatment eventually achieve clearance in equal proportions, twice-weekly treatments appear to take about 1.5 times longer to achieve skin disease clearance as compared with thrice-weekly treatments.12Cameron H. Dawe R.S. Yule S. Murphy J. Ibbotson S.H. Ferguson J. A randomized, observer-blinded trial of twice vs. three times weekly narrowband ultraviolet B phototherapy for chronic plaque psoriasis.Br J Dermatol. 2002; 147: 973-978Crossref PubMed Scopus (0) Google Scholar More specifically, patients receiving twice-weekly NB-UVB treatments achieve clearance in a mean of 88 days compared with 58 days for those receiving 3 treatments per week.12Cameron H. Dawe R.S. Yule S. Murphy J. Ibbotson S.H. Ferguson J. A randomized, observer-blinded trial of twice vs. three times weekly narrowband ultraviolet B phototherapy for chronic plaque psoriasis.Br J Dermatol. 2002; 147: 973-978Crossref PubMed

Over the past 2 decades, considerable progress has been made to further elucidate the complex pathogenesis of psoriasis, facilitating the development of a new armamentarium of more effective, targeted therapies. Despite these important advances, substantial deficits remain in our understanding of psoriasis and its treatment, necessitating further research in many areas. In the sixth section of the American Academy of Dermatology Psoriasis Guidelines of Care, gaps in research and care were identified. We discuss the most important gaps in research that currently exist and make suggestions for studies that should be performed to address these deficits. These encompass both basic science and clinical research studies, including large, prospective epidemiologic studies to determine the true prevalence and natural history of psoriasis; further molecular studies in patients with psoriatic and psoriatic arthritis to understand the function of psoriasis susceptibility genes and to identify novel therapeutic targets; studies to examine the role of environmental factors in the development of psoriasis; further investigation of the relationship between psoriasis and cardiometabolic disease; studies that examine the role of adjunctive therapies such as psychological interventions in appropriate patient groups; and finally, studies to identify biomarkers of disease severity and treatment response to optimize patient therapy.

Advancements in phosphodiesterase (PDE)-targeted therapies have shown promise in recent years for treating patients with a variety of autoimmune diseases. This review summarizes the development of PDE4 inhibitors and the associated literature with a focus on treatments for autoimmune diseases. After the initial investigations of the prototypic PDE inhibitor, rolipram, more selective inhibitors targeting the PDE4 isozyme have been developed. With phase II and phase III clinical trials currently underway to evaluate the safety and efficacy of the latest generation of PDE4 inhibitors, namely apremilast, a new class of treatments may be around the corner for patients suffering from chronic, autoimmune diseases.

To evaluate the efficacy and safety of ustekinumab through 2 years in adult patients with active psoriatic arthritis (PsA).A total of 615 adult patients with active PsA were randomized to placebo, ustekinumab 45 mg, or ustekinumab 90 mg, at weeks 0, 4, and every 12 weeks through week 88 (last dose). At week 16, patients with <5% improvement in both tender and swollen joint counts entered blinded early escape (placebo to 45 mg, 45 mg to 90 mg, and 90 mg to 90 mg). All remaining placebo patients crossed over to ustekinumab 45 mg at week 24. Clinical efficacy measures included American College of Rheumatology criteria for 20% improvement (ACR20), Disease Activity Score in 28 joints using the C-reactive protein level (DAS28-CRP), and ≥75% improvement in the Psoriasis Area and Severity Index (PASI75). Radiographic progression was evaluated using the modified Sharp/van der Heijde score (SHS).At week 100, ACR20, DAS28-CRP moderate/good response, and PASI75 rates ranged from 56.7-63.6%, 71.9-76.7%, and 63.9-72.5%, respectively, across the 3 treatment groups. In both ustekinumab groups, the median percent improvement in dactylitis and enthesitis was 100% at week 100. The mean changes in SHS score from week 52 to week 100 were similar to those observed from week 0 to week 52 in the ustekinumab groups. Through week 108, 70.7% and 9.7% of patients had an adverse event (AE) or serious AE, respectively. The rates and type of AEs were similar between the dose groups.Clinical and radiographic benefits from ustekinumab treatment were maintained through week 100 in the PSUMMIT 1 study. No unexpected safety events were observed; the safety profile of ustekinumab in this population was similar to that previously observed in psoriasis patients treated with ustekinumab.

Genital psoriasis (GenPs) is a common, debilitating and difficult-to-treat manifestation of plaque psoriasis. However, few controlled, interventional studies of GenPs exist.To determine the efficacy of ixekizumab vs. placebo in patients with moderate-to-severe GenPs with ≥ 1% involved body surface area (BSA).Patients with moderate-to-severe GenPs, defined as a baseline static Physician's Global Assessment of Genitalia (sPGA-G) score of ≥ 3, with BSA ≥ 1% were randomized 1 : 1 to receive placebo (n = 74) or the recommended dosing of ixekizumab (n = 75). Major outcomes included the percentage of patients achieving 0 or 1 scores on the sPGA-G (primary end point), overall sPGA, GenPs Sexual Frequency Questionnaire (GenPs-SFQ) item 2, and ≥ 3-point improvement from baseline on the GenPs itch numerical rating scale.At week 12, ixekizumab was superior to placebo for sPGA-G 0/1 (73% vs. 8%, P < 0·001), overall sPGA 0/1 (73% vs. 3%, P < 0·001), GenPs-SFQ item 2 score of 0 or 1 (78% vs. 21%, P < 0·001) and genital itch (60% vs. 8%, P < 0·001). No candidiasis was reported, no deaths occurred and one (1%) serious adverse event was reported in a patient receiving placebo.Ixekizumab was superior to placebo for the treatment of moderate-to-severe GenPs with BSA ≥ 1%. The safety profile of ixekizumab was consistent with previous studies in moderate-to-severe plaque psoriasis.

Psoriasis is a complex inflammatory skin condition associated with serious medical comorbidities in adults, including obesity, hypertension, dyslipidemia, type 2 diabetes mellitus, psoriatic arthritis, nonalcoholic fatty liver disease, depression, anxiety, and decreased quality of life. Because psoriasis begins in childhood in almost one-third of patients, early identification of risk may be critical to minimizing effects on future health.To develop the first set of guidelines for comorbidity screening for patients with pediatric psoriasis based on current evidence.A literature review was performed using PubMed from January 1999 through December 2015. Limiting the search to human studies published in English and removing reviews and editorials produced 153 relevant manuscripts. An expert panel in psoriasis, pediatric dermatology, pediatric rheumatology, pediatric gastroenterology, pediatric endocrinology, and adult and pediatric cardiology used the patient-centered Strength of Recommendation Taxonomy (SORT) method to evaluate and grade the quality of evidence.Because of the limited number of pediatric studies published on these topics, the strength of the panel's recommendations is classified as SORT level C expert consensus recommendations. The majority of recommendations coincide with those endorsed by the American Academy of Pediatrics for the general pediatric patient but with added attention to signs and symptoms of arthritis, depression, and anxiety. The panel also identified key areas for further investigation.Patients with pediatric psoriasis should receive routine screening and identification of risk factors for associated comorbidities. These guidelines are relevant for all health care providers caring for patients with pediatric psoriasis, including primary care clinicians, dermatologists, and pediatric specialists. Because these are the first pediatric guidelines, re-review and refinement will be necessary as studies further detail, and possibly stratify, risk in affected children.

Objective Guselkumab, a human monoclonal antibody specific to interleukin‐23p19, demonstrated efficacy and safety versus placebo through week 24 of the phase III DISCOVER‐2 trial in biologic‐naive patients with psoriatic arthritis (PsA). Here we report 1‐year DISCOVER‐2 findings. Methods Adults with active PsA (≥5 swollen and ≥5 tender joints; C‐reactive protein level ≥0.6 mg/dl) despite standard nonbiologic treatment were randomized to receive subcutaneous injections of guselkumab 100 mg every 4 weeks, guselkumab 100 mg at week 0, week 4 and every 8 weeks thereafter, or placebo with crossover to guselkumab 100 mg every 4 weeks at week 24. We primarily evaluated clinical efficacy through week 52 by imputing missing data (nonresponse for categorical end points; no change/using multiple imputation for continuous end points). Observed radiographic scores and adverse events (AEs) were summarized. Results Of 739 randomized, treated patients, 93% completed week 52. The proportions of patients in whom a ≥20% improvement from baseline in American College of Rheumatology criteria (ACR20) was achieved were maintained after week 24, reaching 71% (173 of 245) and 75% (185 of 248) for patients randomized to receive treatment every 4 weeks or every 8 weeks, respectively, by week 52. The proportions of patients in whom ACR50/ACR70 and skin responses, minimal or very low disease activity, and dactylitis or enthesitis resolution were achieved at week 24 were also maintained through week 52. Further, low levels of radiographic progression, along with improvements in physical function and health‐related quality of life, were sustained through week 52 with continued guselkumab treatment. Few patients experienced serious infections through week 52, with no evidence of a dosing regimen response or increase from weeks 0–24 (4 of 493 [0.8%]) to weeks 24–52 (3 of 493 [0.6%]) among guselkumab‐randomized patients. No patient developed an opportunistic infection or died. Conclusion In biologic‐naive PsA patients, guselkumab provided sustained improvements across diverse manifestations and maintained a favorable risk–benefit profile through week 52.

Objectives To evaluate efficacy and safety of the anti-interleukin-23p19 monoclonal antibody tildrakizumab in patients with psoriatic arthritis (PsA). Methods In this randomised, double-blind, placebo-controlled, phase IIb study, patients with active PsA were randomised 1:1:1:1:1 to tildrakizumab 200 mg every 4 weeks (Q4W); tildrakizumab 200, 100 or 20 mg Q12W; or placebo Q4W. Patients receiving tildrakizumab 20 mg or placebo switched to tildrakizumab 200 mg Q12W at W24; treatment continued to W52. The primary efficacy endpoint was proportion of patients with ACR20 response (≥20% improvement by American College of Rheumatology criteria) at W24. Secondary efficacy endpoints were assessed without adjustment for multiplicity. Safety was evaluated from treatment-emergent adverse events (TEAEs). Results 391/500 patients screened were randomised and treated. At W24, 71.4%–79.5% of tildrakizumab-treated versus 50.6% of placebo-treated patients achieved ACR20 (all p&lt;0.01). Patients receiving tildrakizumab versus placebo generally achieved higher rates of ACR50, Disease Activity Score in 28 joints with C reactive protein &lt;3.2, minimal disease activity and 75%/90%/100% improvement from baseline Psoriasis Area and Severity Index responses at W24 and through W52. Improvement in dactylitis and enthesitis was not observed; results were mixed for other outcomes. Responses in patients switched to tildrakizumab 200 mg at W24 were consistent with treatment from baseline. TEAEs and serious TEAEs occurred in 64.5% and 3.3%, respectively, of all patients through W52 and were comparable among treatment arms. Conclusions Tildrakizumab treatment significantly improved joint and skin manifestations of PsA other than dactylitis and enthesitis. Treatment was generally well tolerated through W52. Clinicaltrials.gov NCT02980692 .

Psoriasis is a chronic, immune-mediated, systemic, inflammatory disorder characterized by skin plaques and, often, nail disease and arthritis that contribute to reduced quality of life. Psoriatic arthritis—a heterogeneous, inflammatory, musculoskeletal disease that can cause permanent damage to both peripheral and axial joints—is the most common comorbidity of psoriasis. Axial disease occurs in 25% to 70% of patients with PsA, with some patients exclusively experiencing axial joint involvement. Early therapeutic intervention is important for preventing permanent joint and spine damage and loss of functionality in these patients. Because skin symptoms associated with psoriasis often precede psoriatic arthritis, dermatologists are uniquely positioned to play an important role in identifying and treating patients with psoriatic arthritis. Proactive screening of patients with all severities of psoriasis for the signs and symptoms of psoriatic arthritis is key to early diagnosis and intervention. In this review, we discuss the clinical presentation, risk factors, and treatment options for psoriatic arthritis with axial involvement, with the aim of helping dermatologists understand the disease and identify patients who might benefit from further assessment, treatment, and/or referral to a rheumatology practice. Psoriasis is a chronic, immune-mediated, systemic, inflammatory disorder characterized by skin plaques and, often, nail disease and arthritis that contribute to reduced quality of life. Psoriatic arthritis—a heterogeneous, inflammatory, musculoskeletal disease that can cause permanent damage to both peripheral and axial joints—is the most common comorbidity of psoriasis. Axial disease occurs in 25% to 70% of patients with PsA, with some patients exclusively experiencing axial joint involvement. Early therapeutic intervention is important for preventing permanent joint and spine damage and loss of functionality in these patients. Because skin symptoms associated with psoriasis often precede psoriatic arthritis, dermatologists are uniquely positioned to play an important role in identifying and treating patients with psoriatic arthritis. Proactive screening of patients with all severities of psoriasis for the signs and symptoms of psoriatic arthritis is key to early diagnosis and intervention. In this review, we discuss the clinical presentation, risk factors, and treatment options for psoriatic arthritis with axial involvement, with the aim of helping dermatologists understand the disease and identify patients who might benefit from further assessment, treatment, and/or referral to a rheumatology practice. Capsule Summary•Psoriasis is an inflammatory immune disease associated with psoriatic arthritis, a disease that can involve peripheral and axial joints and cause permanent joint damage and loss of function if untreated.•Dermatologists play an important role in the early diagnosis and treatment of psoriatic arthritis by proactively screening patients with psoriasis. •Psoriasis is an inflammatory immune disease associated with psoriatic arthritis, a disease that can involve peripheral and axial joints and cause permanent joint damage and loss of function if untreated.•Dermatologists play an important role in the early diagnosis and treatment of psoriatic arthritis by proactively screening patients with psoriasis. Psoriasis is a chronic, inflammatory, immune-mediated skin disorder associated with significant morbidity, reduced quality of life (QOL), and mortality1Helmick C.G. Lee-Han H. Hirsch S.C. Baird T.L. Bartlett C.L. Prevalence of psoriasis among adults in the U.S.: 2003-2006 and 2009-2010 National Health and Nutrition Examination Surveys.Am J Prev Med. 2014; 47: 37-45Abstract Full Text Full Text PDF PubMed Scopus (127) Google Scholar, 2Krueger G. Koo J. Lebwohl M. Menter A. Stern R.S. Rolstad T. The impact of psoriasis on quality of life: results of a 1998 National Psoriasis Foundation patient-membership survey.Arch Dermatol. 2001; 137: 280-284PubMed Google Scholar, 3Rachakonda T.D. Schupp C.W. Armstrong A.W. Psoriasis prevalence among adults in the United States.J Am Acad Dermatol. 2014; 70: 512-516Abstract Full Text Full Text PDF PubMed Scopus (480) Google Scholar that affects approximately 7.4 million adults in the United States.3Rachakonda T.D. Schupp C.W. Armstrong A.W. Psoriasis prevalence among adults in the United States.J Am Acad Dermatol. 2014; 70: 512-516Abstract Full Text Full Text PDF PubMed Scopus (480) Google Scholar Comorbidities are common in patients with psoriasis, and psoriatic arthritis (PsA) is one of the most frequently observed.4Elmets C.A. Leonardi C.L. Davis D.M.R. et al.Joint AAD-NPF guidelines of care for the management and treatment of psoriasis with awareness and attention to comorbidities.J Am Acad Dermatol. 2019; 80: 1073-1113Abstract Full Text Full Text PDF PubMed Scopus (90) Google Scholar Approximately 25% to 30% of patients with psoriasis develop PsA,5Alinaghi F. Calov M. Kristensen L.E. et al.Prevalence of psoriatic arthritis in patients with psoriasis: a systematic review and meta-analysis of observational and clinical studies.J Am Acad Dermatol. 2019; 80: 251-265Abstract Full Text Full Text PDF PubMed Scopus (129) Google Scholar,6Mease P.J. Gladman D.D. Papp K.A. et al.Prevalence of rheumatologist-diagnosed psoriatic arthritis in patients with psoriasis in European/North American dermatology clinics.J Am Acad Dermatol. 2013; 69: 729-735Abstract Full Text Full Text PDF PubMed Scopus (255) Google Scholar an inflammatory, seronegative, musculoskeletal disease that can involve the joints, entheses, or spine.7Taylor W. Gladman D. Helliwell P. et al.Classification criteria for psoriatic arthritis: development of new criteria from a large international study.Arthritis Rheum. 2006; 54: 2665-2673Crossref PubMed Scopus (2121) Google Scholar Characteristics of PsA are heterogeneous and include nail and skin changes, peripheral arthritis, enthesitis, dactylitis, and axial spondyloarthritis (SpA)8Sieper J. Poddubnyy D. Axial spondyloarthritis.Lancet. 2017; 390: 73-84Abstract Full Text Full Text PDF PubMed Scopus (343) Google Scholar,9Coates L.C. Helliwell P.S. Psoriatic arthritis: state of the art review.Clin Med (Lond). 2017; 17: 65-70Crossref PubMed Scopus (72) Google Scholar; the symptoms can present alone or in combination with one another.10Coates L.C. Kavanaugh A. Mease P.J. et al.Group for Research and Assessment of Psoriasis and Psoriatic Arthritis 2015 treatment recommendations for psoriatic arthritis.Arthritis Rheumatol. 2016; 68: 1060-1071PubMed Google Scholar PsA affects men and women equally, and it commonly develops when patients are 30 to 50 years old.11Gottlieb A. Korman N.J. Gordon K.B. et al.Guidelines of care for the management of psoriasis and psoriatic arthritis: section 2. Psoriatic arthritis: overview and guidelines of care for treatment with an emphasis on the biologics.J Am Acad Dermatol. 2008; 58: 851-864Abstract Full Text Full Text PDF PubMed Scopus (350) Google Scholar Like psoriasis, PsA is associated with multiple comorbidities, including cardiovascular disease, metabolic syndrome, obesity, diabetes, depression, uveitis, and anxiety.12Ogdie A. Schwartzman S. Husni M.E. Recognizing and managing comorbidities in psoriatic arthritis.Curr Opin Rheumatol. 2015; 27: 118-126Crossref PubMed Scopus (107) Google Scholar PsA is a potentially erosive disease, and approximately 50% of patients exhibit structural damage and functional impairment within 2 years of initial assessment13Kane D. Stafford L. Bresnihan B. FitzGerald O. A prospective, clinical and radiological study of early psoriatic arthritis: an early synovitis clinic experience.Rheumatology (Oxford). 2003; 42: 1460-1468Crossref PubMed Scopus (424) Google Scholar; many patients experience irreversible joint damage and disability with disease progression.14Husted J.A. Tom B.D. Farewell V.T. Schentag C.T. Gladman D.D. A longitudinal study of the effect of disease activity and clinical damage on physical function over the course of psoriatic arthritis: does the effect change over time?.Arthritis Rheum. 2007; 56: 840-849Crossref PubMed Scopus (70) Google Scholar,15Mease P. van der Heijde D. Landewé R. et al.Secukinumab improves active psoriatic arthritis symptoms and inhibits radiographic progression: primary results from the randomised, double-blind, phase III FUTURE 5 study.Ann Rheum Dis. 2018; 77: 890-897PubMed Google Scholar Axial involvement occurs in 25% to 70% of patients with PsA,11Gottlieb A. Korman N.J. Gordon K.B. et al.Guidelines of care for the management of psoriasis and psoriatic arthritis: section 2. Psoriatic arthritis: overview and guidelines of care for treatment with an emphasis on the biologics.J Am Acad Dermatol. 2008; 58: 851-864Abstract Full Text Full Text PDF PubMed Scopus (350) Google Scholar,16Gladman D.D. Axial disease in psoriatic arthritis.Curr Rheumatol Rep. 2007; 9: 455-460Crossref PubMed Scopus (81) Google Scholar with exclusive axial involvement in 5% of patients.11Gottlieb A. Korman N.J. Gordon K.B. et al.Guidelines of care for the management of psoriasis and psoriatic arthritis: section 2. Psoriatic arthritis: overview and guidelines of care for treatment with an emphasis on the biologics.J Am Acad Dermatol. 2008; 58: 851-864Abstract Full Text Full Text PDF PubMed Scopus (350) Google Scholar Common symptoms include inflammatory back pain (eg, pain that improves with activity but worsens with rest, morning stiffness lasting >30 minutes).11Gottlieb A. Korman N.J. Gordon K.B. et al.Guidelines of care for the management of psoriasis and psoriatic arthritis: section 2. Psoriatic arthritis: overview and guidelines of care for treatment with an emphasis on the biologics.J Am Acad Dermatol. 2008; 58: 851-864Abstract Full Text Full Text PDF PubMed Scopus (350) Google Scholar,17Baraliakos X. Coates L.C. Braun J. The involvement of the spine in psoriatic arthritis.Clin Exp Rheumatol. 2015; 33: S31-S35PubMed Google Scholar The diagnosis is confirmed by physical examination and imaging (eg, sacroiliitis, spinal ossifications).11Gottlieb A. Korman N.J. Gordon K.B. et al.Guidelines of care for the management of psoriasis and psoriatic arthritis: section 2. Psoriatic arthritis: overview and guidelines of care for treatment with an emphasis on the biologics.J Am Acad Dermatol. 2008; 58: 851-864Abstract Full Text Full Text PDF PubMed Scopus (350) Google Scholar,17Baraliakos X. Coates L.C. Braun J. The involvement of the spine in psoriatic arthritis.Clin Exp Rheumatol. 2015; 33: S31-S35PubMed Google Scholar Among patients with axial PsA, cervical spinal mobility and lateral flexion significantly decrease within 5 years if untreated.18Chandran V. Barrett J. Schentag C.T. Farewell V.T. Gladman D.D. Axial psoriatic arthritis: update on a longterm prospective study.J Rheumatol. 2009; 36: 2744-2750Crossref PubMed Scopus (69) Google Scholar Additionally, sacroiliitis worsens with time; 37% and 52% of patients develop grade 2 or higher sacroiliitis within 5 and 10 years, respectively.18Chandran V. Barrett J. Schentag C.T. Farewell V.T. Gladman D.D. Axial psoriatic arthritis: update on a longterm prospective study.J Rheumatol. 2009; 36: 2744-2750Crossref PubMed Scopus (69) Google Scholar Therefore, early identification and treatment of patients with axial PsA is critical. Cutaneous manifestations of psoriasis can precede the onset of PsA by approximately 3 to 8 years,19Tascilar K. Aydin S.Z. Akar S. et al.Delay between the onset of psoriasis and arthritis in PsA patients from the PsART international cohort [abstract].Arthritis Rheumatol. 2019; 71: 2854Google Scholar and 1% to 3% of patients with psoriasis develop PsA annually.5Alinaghi F. Calov M. Kristensen L.E. et al.Prevalence of psoriatic arthritis in patients with psoriasis: a systematic review and meta-analysis of observational and clinical studies.J Am Acad Dermatol. 2019; 80: 251-265Abstract Full Text Full Text PDF PubMed Scopus (129) Google Scholar,20Christophers E. Barker J.N. Griffiths C.E. et al.The risk of psoriatic arthritis remains constant following initial diagnosis of psoriasis among patients seen in European dermatology clinics.J Eur Acad Dermatol Venereol. 2010; 24: 548-554Crossref PubMed Scopus (99) Google Scholar Therefore, dermatologists play a critical role in early detection for patients with PsA.11Gottlieb A. Korman N.J. Gordon K.B. et al.Guidelines of care for the management of psoriasis and psoriatic arthritis: section 2. Psoriatic arthritis: overview and guidelines of care for treatment with an emphasis on the biologics.J Am Acad Dermatol. 2008; 58: 851-864Abstract Full Text Full Text PDF PubMed Scopus (350) Google Scholar However, PsA is frequently underdiagnosed, with up to 41% of patients with psoriasis treated at dermatology centers having undiagnosed PsA.6Mease P.J. Gladman D.D. Papp K.A. et al.Prevalence of rheumatologist-diagnosed psoriatic arthritis in patients with psoriasis in European/North American dermatology clinics.J Am Acad Dermatol. 2013; 69: 729-735Abstract Full Text Full Text PDF PubMed Scopus (255) Google Scholar,21Haroon M. Kirby B. FitzGerald O. High prevalence of psoriatic arthritis in patients with severe psoriasis with suboptimal performance of screening questionnaires.Ann Rheum Dis. 2013; 72: 736-740Crossref PubMed Scopus (187) Google Scholar To address this problem, the new American Academy of Dermatology/National Psoriasis Foundation guidelines emphasize the role of dermatologists in recognizing PsA and recommend proactive screening of patients.4Elmets C.A. Leonardi C.L. Davis D.M.R. et al.Joint AAD-NPF guidelines of care for the management and treatment of psoriasis with awareness and attention to comorbidities.J Am Acad Dermatol. 2019; 80: 1073-1113Abstract Full Text Full Text PDF PubMed Scopus (90) Google Scholar Therefore, it is important that dermatologists be familiar with the signs of PsA, including those associated with axial involvement. Here, we review axial PsA and describe its clinical presentation, risk factors, pathology, and treatment options. Axial involvement in PsA usually occurs in young patients (<40 years old).22Jadon D.R. Sengupta R. Nightingale A. et al.Axial disease in psoriatic arthritis study: defining the clinical and radiographic phenotype of psoriatic spondyloarthritis.Ann Rheum Dis. 2017; 76: 701-707Crossref PubMed Scopus (73) Google Scholar Although axial PsA had been thought to be more prevalent in men, an analysis of the US Corrona PsA/Spondyloarthritis Registry—which compared patients with PsA with and without axial involvement—found no significant differences in the proportion of men and women with axial involvement.23Mease P.J. Palmer J.B. Liu M. et al.Influence of axial involvement on clinical characteristics of psoriatic arthritis: analysis from the Corrona Psoriatic Arthritis/Spondyloarthritis Registry.J Rheumatol. 2018; 45: 1389-1396Crossref PubMed Scopus (42) Google Scholar Most patients with PsA have preceding psoriasis, but a small percentage (approximately 15%) have no psoriasis at diagnosis.24Ritchlin C.T. Colbert R.A. Gladman D.D. Psoriatic arthritis.N Engl J Med. 2017; 376: 957-970Crossref PubMed Scopus (439) Google Scholar That proportion may be lower if one includes inverse/intertriginous psoriasis, which occurs in less frequently examined areas of body folds.25Merola J.F. Li T. Li W.Q. Cho E. Qureshi A.A. Prevalence of psoriasis phenotypes among men and women in the USA.Clin Exp Dermatol. 2016; 41: 486-489Crossref PubMed Scopus (30) Google Scholar Patients with PsA can also present with enthesitis, dactylitis (sausage digit), nail changes, and peripheral arthritis.11Gottlieb A. Korman N.J. Gordon K.B. et al.Guidelines of care for the management of psoriasis and psoriatic arthritis: section 2. Psoriatic arthritis: overview and guidelines of care for treatment with an emphasis on the biologics.J Am Acad Dermatol. 2008; 58: 851-864Abstract Full Text Full Text PDF PubMed Scopus (350) Google Scholar,22Jadon D.R. Sengupta R. Nightingale A. et al.Axial disease in psoriatic arthritis study: defining the clinical and radiographic phenotype of psoriatic spondyloarthritis.Ann Rheum Dis. 2017; 76: 701-707Crossref PubMed Scopus (73) Google Scholar,23Mease P.J. Palmer J.B. Liu M. et al.Influence of axial involvement on clinical characteristics of psoriatic arthritis: analysis from the Corrona Psoriatic Arthritis/Spondyloarthritis Registry.J Rheumatol. 2018; 45: 1389-1396Crossref PubMed Scopus (42) Google Scholar,26Perez Alamino R. Maldonado Cocco J.A. Citera G. et al.Differential features between primary ankylosing spondylitis and spondylitis associated with psoriasis and inflammatory bowel disease.J Rheumatol. 2011; 38: 1656-1660Crossref PubMed Scopus (48) Google Scholar Typical symptoms of axial PsA include morning back/neck stiffness that lasts longer than 30 minutes and neck or back pain that improves with activity and worsens after prolonged inactivity,11Gottlieb A. Korman N.J. Gordon K.B. et al.Guidelines of care for the management of psoriasis and psoriatic arthritis: section 2. Psoriatic arthritis: overview and guidelines of care for treatment with an emphasis on the biologics.J Am Acad Dermatol. 2008; 58: 851-864Abstract Full Text Full Text PDF PubMed Scopus (350) Google Scholar,17Baraliakos X. Coates L.C. Braun J. The involvement of the spine in psoriatic arthritis.Clin Exp Rheumatol. 2015; 33: S31-S35PubMed Google Scholar,18Chandran V. Barrett J. Schentag C.T. Farewell V.T. Gladman D.D. Axial psoriatic arthritis: update on a longterm prospective study.J Rheumatol. 2009; 36: 2744-2750Crossref PubMed Scopus (69) Google Scholar,23Mease P.J. Palmer J.B. Liu M. et al.Influence of axial involvement on clinical characteristics of psoriatic arthritis: analysis from the Corrona Psoriatic Arthritis/Spondyloarthritis Registry.J Rheumatol. 2018; 45: 1389-1396Crossref PubMed Scopus (42) Google Scholar which are defining features of inflammatory neck/back pain (Fig 1),27Rudwaleit M. Metter A. Listing J. Sieper J. Braun J. Inflammatory back pain in ankylosing spondylitis: a reassessment of the clinical history for application as classification and diagnostic criteria.Arthritis Rheum. 2006; 54: 569-578Crossref PubMed Scopus (379) Google Scholar,28Sieper J. van der Heijde D. Landewe R. et al.New criteria for inflammatory back pain in patients with chronic back pain: a real patient exercise by experts from the Assessment of SpondyloArthritis International Society (ASAS).Ann Rheum Dis. 2009; 68: 784-788Crossref PubMed Scopus (359) Google Scholar as well as limited mobility.17Baraliakos X. Coates L.C. Braun J. The involvement of the spine in psoriatic arthritis.Clin Exp Rheumatol. 2015; 33: S31-S35PubMed Google Scholar However, 20% of patients show no symptoms of axial involvement18Chandran V. Barrett J. Schentag C.T. Farewell V.T. Gladman D.D. Axial psoriatic arthritis: update on a longterm prospective study.J Rheumatol. 2009; 36: 2744-2750Crossref PubMed Scopus (69) Google Scholar,29Queiro R. Belzunegui J. Gonzalez C. et al.Clinically asymptomatic axial disease in psoriatic spondyloarthropathy. A retrospective study.Clin Rheumatol. 2002; 21: 10-13Crossref PubMed Scopus (58) Google Scholar; these patients are usually diagnosed with PsA because they present with other PsA-related symptoms, such as dactylitis or arthritis.29Queiro R. Belzunegui J. Gonzalez C. et al.Clinically asymptomatic axial disease in psoriatic spondyloarthropathy. A retrospective study.Clin Rheumatol. 2002; 21: 10-13Crossref PubMed Scopus (58) Google Scholar,30Cohen J.M. Husni M.E. Qureshi A.A. Merola J.F. Psoriatic arthritis: it's as easy as “PSA”.J Am Acad Dermatol. 2015; 72: 905-906Abstract Full Text Full Text PDF PubMed Scopus (11) Google Scholar Sacroiliitis is a common feature of axial PsA (25%-50% of patients)31Gladman D.D. Clinical, radiological, and functional assessment in psoriatic arthritis: is it different from other inflammatory joint diseases?.Ann Rheum Dis. 2006; 65: iii22-iii24PubMed Google Scholar, 32Haroon M. Winchester R. Giles J.T. Heffernan E. FitzGerald O. Clinical and genetic associations of radiographic sacroiliitis and its different patterns in psoriatic arthritis.Clin Exp Rheumatol. 2017; 35: 270-276PubMed Google Scholar, 33Williamson L. Dockerty J.L. Dalbeth N. McNally E. Ostlere S. Wordsworth B.P. Clinical assessment of sacroiliitis and HLA-B27 are poor predictors of sacroiliitis diagnosed by magnetic resonance imaging in psoriatic arthritis.Rheumatology (Oxford). 2004; 43: 85-88Crossref PubMed Scopus (93) Google Scholar and is frequently asymmetric (73% of patients).32Haroon M. Winchester R. Giles J.T. Heffernan E. FitzGerald O. Clinical and genetic associations of radiographic sacroiliitis and its different patterns in psoriatic arthritis.Clin Exp Rheumatol. 2017; 35: 270-276PubMed Google Scholar Patients may present with alternating pain over the sacroiliac joint/buttock, with the pain typically lasting longer than 20 minutes and being worse during the second half of the night (Fig 1).27Rudwaleit M. Metter A. Listing J. Sieper J. Braun J. Inflammatory back pain in ankylosing spondylitis: a reassessment of the clinical history for application as classification and diagnostic criteria.Arthritis Rheum. 2006; 54: 569-578Crossref PubMed Scopus (379) Google Scholar,33Williamson L. Dockerty J.L. Dalbeth N. McNally E. Ostlere S. Wordsworth B.P. Clinical assessment of sacroiliitis and HLA-B27 are poor predictors of sacroiliitis diagnosed by magnetic resonance imaging in psoriatic arthritis.Rheumatology (Oxford). 2004; 43: 85-88Crossref PubMed Scopus (93) Google Scholar,34van den Berg R. de Hooge M. Rudwaleit M. et al.ASAS modification of the Berlin algorithm for diagnosing axial spondyloarthritis: results from the Spondyloarthritis Caught Early (SPACE)-cohort and from the Assessment of Spondyloarthritis international Society (ASAS)-cohort.Ann Rheum Dis. 2013; 72: 1646-1653Crossref PubMed Scopus (91) Google Scholar Sacroiliitis can be assessed clinically by asking simple questions (eg, “Is your pain worse at night?” or “How long does your pain typically last?”) to determine if a patient's symptoms are characteristic of inflammatory sacroiliac joint pain (Fig 1). Comorbidities are common, with psoriasis being the most frequent (80% of patients).9Coates L.C. Helliwell P.S. Psoriatic arthritis: state of the art review.Clin Med (Lond). 2017; 17: 65-70Crossref PubMed Scopus (72) Google Scholar Other comorbidities of axial PsA include uveitis and inflammatory bowel disease (IBD). Uveitis occurs in 6% to 7% of patients with PsA but is more common (up to 33%) in those with axial involvement.35Paiva E.S. Macaluso D.C. Edwards A. Rosenbaum J.T. Characterisation of uveitis in patients with psoriatic arthritis.Ann Rheum Dis. 2000; 59: 67-70Crossref PubMed Scopus (109) Google Scholar Uveitis in axial PsA is more common in men, in younger patients (aged <34 years), and in those positive for human leukocyte antigen (HLA)-B27.35Paiva E.S. Macaluso D.C. Edwards A. Rosenbaum J.T. Characterisation of uveitis in patients with psoriatic arthritis.Ann Rheum Dis. 2000; 59: 67-70Crossref PubMed Scopus (109) Google Scholar IBD occurs in 11% of patients with axial PsA and is significantly more common in patients with axial involvement than in those with peripheral-only PsA (2%).22Jadon D.R. Sengupta R. Nightingale A. et al.Axial disease in psoriatic arthritis study: defining the clinical and radiographic phenotype of psoriatic spondyloarthritis.Ann Rheum Dis. 2017; 76: 701-707Crossref PubMed Scopus (73) Google Scholar Axial PsA has a significant impact on QOL and is associated with worse disease than that seen in patients without axial involvement.23Mease P.J. Palmer J.B. Liu M. et al.Influence of axial involvement on clinical characteristics of psoriatic arthritis: analysis from the Corrona Psoriatic Arthritis/Spondyloarthritis Registry.J Rheumatol. 2018; 45: 1389-1396Crossref PubMed Scopus (42) Google Scholar In an analysis of the US Corrona Registry, patients with axial involvement had more severe skin manifestations, higher tender joint counts, more enthesitis, and worse disease activity.23Mease P.J. Palmer J.B. Liu M. et al.Influence of axial involvement on clinical characteristics of psoriatic arthritis: analysis from the Corrona Psoriatic Arthritis/Spondyloarthritis Registry.J Rheumatol. 2018; 45: 1389-1396Crossref PubMed Scopus (42) Google Scholar Similarly, patients with axial PsA had worse pain than patients without axial involvement and had significantly impaired physical function and QOL (P < .001).23Mease P.J. Palmer J.B. Liu M. et al.Influence of axial involvement on clinical characteristics of psoriatic arthritis: analysis from the Corrona Psoriatic Arthritis/Spondyloarthritis Registry.J Rheumatol. 2018; 45: 1389-1396Crossref PubMed Scopus (42) Google Scholar Patients with axial involvement also had decreased work productivity, with significantly higher proportions of missed work time (10.0% vs 3.3%), overall work impairment (32.3% vs 16.8%) and overall activity impairment (37.0% vs 18.1%; P < .001 for all). Problems with walking and self-care and feelings of anxiety and depression were also common.23Mease P.J. Palmer J.B. Liu M. et al.Influence of axial involvement on clinical characteristics of psoriatic arthritis: analysis from the Corrona Psoriatic Arthritis/Spondyloarthritis Registry.J Rheumatol. 2018; 45: 1389-1396Crossref PubMed Scopus (42) Google Scholar Clinical factors associated with axial PsA include more-severe skin psoriasis, a young age at PsA onset, and severe peripheral arthritis. In 1 study, severe skin psoriasis (P = .041) and younger age at PsA onset (P < .001) correlated with developing sacroiliitis.32Haroon M. Winchester R. Giles J.T. Heffernan E. FitzGerald O. Clinical and genetic associations of radiographic sacroiliitis and its different patterns in psoriatic arthritis.Clin Exp Rheumatol. 2017; 35: 270-276PubMed Google Scholar Additionally, peripheral joint erosions were more common in patients with asymmetric sacroiliitis, suggesting a possible association between peripheral arthritis and axial involvement in patients with PsA.32Haroon M. Winchester R. Giles J.T. Heffernan E. FitzGerald O. Clinical and genetic associations of radiographic sacroiliitis and its different patterns in psoriatic arthritis.Clin Exp Rheumatol. 2017; 35: 270-276PubMed Google Scholar This association was further suggested by another study in which radiographic damage to peripheral joints increased the risk of developing axial PsA.36Chandran V. Tolusso D.C. Cook R.J. Gladman D.D. Risk factors for axial inflammatory arthritis in patients with psoriatic arthritis.J Rheumatol. 2010; 37: 809-815Crossref PubMed Scopus (56) Google Scholar IBD, a known comorbidity of psoriasis,4Elmets C.A. Leonardi C.L. Davis D.M.R. et al.Joint AAD-NPF guidelines of care for the management and treatment of psoriasis with awareness and attention to comorbidities.J Am Acad Dermatol. 2019; 80: 1073-1113Abstract Full Text Full Text PDF PubMed Scopus (90) Google Scholar is also a risk factor for PsA and other SpAs, with both being more common in patients with Crohn's disease.37Fragoulis G.E. Liava C. Daoussis D. Akriviadis E. Garyfallos A. Dimitroulas T. Inflammatory bowel diseases and spondyloarthropathies: from pathogenesis to treatment.World J Gastroenterol. 2019; 25: 2162-2176Crossref PubMed Scopus (45) Google Scholar,38Halling M.L. Kjeldsen J. Knudsen T. Nielsen J. Hansen L.K. Patients with inflammatory bowel disease have increased risk of autoimmune and inflammatory diseases.World J Gastroenterol. 2017; 23: 6137-6146Crossref PubMed Scopus (71) Google Scholar Sacroiliitis is estimated to occur in 12% to 46% of patients with IBD,37Fragoulis G.E. Liava C. Daoussis D. Akriviadis E. Garyfallos A. Dimitroulas T. Inflammatory bowel diseases and spondyloarthropathies: from pathogenesis to treatment.World J Gastroenterol. 2019; 25: 2162-2176Crossref PubMed Scopus (45) Google Scholar and clinically silent macroscopic and microscopic colitis occur in approximately 60% of patients with axial SpA (axSpA),37Fragoulis G.E. Liava C. Daoussis D. Akriviadis E. Garyfallos A. Dimitroulas T. Inflammatory bowel diseases and spondyloarthropathies: from pathogenesis to treatment.World J Gastroenterol. 2019; 25: 2162-2176Crossref PubMed Scopus (45) Google Scholar emphasizing the gut-axial axis. Uveitis has been identified as a risk factor for PsA, but its role as a risk factor for axial involvement remains unclear.39Eder L. Haddad A. Rosen C.F. et al.The incidence and risk factors for psoriatic arthritis in patients with psoriasis: a prospective cohort study.Arthritis Rheumatol. 2016; 68: 915-923Crossref PubMed Scopus (102) Google Scholar A notable risk factor for axial PsA is the presence of HLA-B27.36Chandran V. Tolusso D.C. Cook R.J. Gladman D.D. Risk factors for axial inflammatory arthritis in patients with psoriatic arthritis.J Rheumatol. 2010; 37: 809-815Crossref PubMed Scopus (56) Google Scholar,40Brewerton D.A. Caffrey M. Nicholls A. Walters D. James D.C. HL-A 27 and arthropathies associated with ulcerative colitis and psoriasis.Lancet. 1974; 1: 956-958Abstract PubMed Scopus (105) Google Scholar HLA-B27 is a known key genetic marker of ankylosing spondylitis (AS), is present in more than 80% of patients with AS, and is the only known genetic marker common to AS and axial PsA.41Feld J. Chandran V. Haroon N. Inman R. Gladman D. Axial disease in psoriatic arthritis and ankylosing spondylitis: a critical comparison.Nat Rev Rheumatol. 2018; 14: 363-371Crossref PubMed Scopus (58) Google Scholar Although its prevalence is lower in patients with PsA (20%),41Feld J. Chandran V. Haroon N. Inman R. Gladman D. Axial disease in psoriatic arthritis and ankylosing spondylitis: a critical comparison.Nat Rev Rheumatol. 2018; 14: 363-371Crossr

Deucravacitinib is an oral, selective tyrosine kinase 2 inhibitor that demonstrated therapeutic benefit in a Phase 2 clinical trial of adults with moderate to severe plaque psoriasis. This analysis was designed to evaluate the effect of deucravacitinib on additional clinical and quality-of-life (QoL) outcomes and assess the relationship between these outcomes in adults with psoriasis. Post-hoc analysis of a 12-week Phase 2 trial was conducted for the three most efficacious dosage groups (3 mg twice daily, 6 mg twice daily, 12 mg once daily) and placebo. Investigator assessments for efficacy included Psoriasis Area and Severity Index (PASI), body surface area (BSA) involvement, and static Physician's Global Assessment; QoL was assessed using the Dermatology Life Quality Index (DLQI). Treatment responses and their associations were evaluated over time. Deucravacitinib elicited improvement versus placebo as early as Week 4 for most efficacy measures (including changes in absolute PASI and BSA), with efficacy trends observed from Week 2 to Week 12. Improvements in QoL, assessed by achievement of a DLQI overall score of 0/1 (no effect at all on patient’s life), followed a pattern similar to deucravacitinib-related clinical outcomes over 12 weeks. Overall, patients with greater improvements in psoriasis-related clinical signs and symptoms also reported greater improvement in QoL. However, complete skin clearance was not required for achieving DLQI 0/1. Deucravacitinib treatment produced early response and similar trends in improvements across multiple efficacy assessments and QoL in moderate to severe plaque psoriasis. Deucravacitinib has the potential to become a promising new oral therapy for this condition. ClinicalTrials.gov identifier; NCT02931838. Psoriasis is a skin disease that affects up to 2% of the population. In psoriasis, red, scaly lesions develop on the skin driven by an aberrant immune response. Psoriasis impacts not only physical and mental health but also quality of life (QoL). Deucravacitinib is being investigated as a treatment for psoriasis. We performed a Phase 2 dose-ranging, placebo-controlled, 12-week study of deucravacitinib in adults with moderate to severe psoriasis. Patients in the USA, Australia, Canada, Germany, Japan, Latvia, Mexico, and Poland participated. The study showed that oral treatment with deucravacitinib was effective using a disease severity score (percentage of patients with ≥ 75% reduction from baseline in Psoriasis Area and Severity Index score) at Week 12—placebo 7% and deucravacitinib 67%–75% for the three highest dosages—and was generally well tolerated. We further analyzed the association between efficacy and a QoL measure, the Dermatology Life Quality Index (DLQI), in patients who received placebo or the most effective dosages of deucravacitinib (≥ 3 mg twice daily). Deucravacitinib was effective at the three dosage levels tested. Skin improvement occurred early during treatment and was mirrored by improvements in DLQI score during the 12 weeks of treatment. Although some patients did not have complete clearance of their psoriasis, a large percentage of those patients still achieved considerable improvement in QoL as measured by achieving a DLQI score of 0/1 (i.e., no effect at all on the patient’s QoL).

Generalized pustular psoriasis (GPP) is a serious, immune-mediated inflammatory skin disease with significant morbidity and mortality. Estimates of GPP prevalence vary between 1.8 and 124 per million people.1 GPP pathogenesis primarily involves abnormal activation of the interleukin (IL)-36 pathway of the innate immune system, with secondary contributions from the adaptive immune system. Through a validated Delphi method,2,3 32 physicians specializing in psoriatic diseases from the Medical Board of the National Psoriasis Foundation formulated the following consensus statements to guide clinicians, payors, and patients in GPP management.

Psoriatic arthritis (PsA) is a chronic inflammatory disease that often goes unrecognized in patients with psoriasis. As a result, patients may develop significant structural damage before diagnosis and initiation of adequate treatment. Dermatologists are in an unique position to identify early signs and symptoms of PsA. Here, we briefly review the pathogenesis of PsA, differences in PsA presentation within real-world dermatology practice versus rheumatology clinical trials, and imaging modalities that can be used to assess structural damage. We then discuss several ongoing controversies related to prediction, assessment, and treatment of PsA-related structural damage. Debated questions include the following: (1) Does subclinical enthesitis predict progression from psoriasis to PsA?, (2) Does methotrexate inhibit progression of structural damage?, (3) Does structural damage correlate with clinical disease activity?, and (4) Can progression from psoriasis to PsA be prevented? Evidence presented herein suggests that dermatologists, together with rheumatologists, can play important roles in the early diagnosis and treatment of PsA, thereby potentially preventing irreversible structural damage.

Infliximab monotherapy provided a rapid and high degree of clinical benefit in patients with moderate to severe psoriasis in a previously conducted trial. Herein we describe the pharmacodynamic and pharmacokinetic results observed in this clinical trial.Patients with psoriasis received 5 or 10 mg/kg of infliximab or placebo at weeks 0, 2, and 6. Immunohistochemical analysis of lesional (weeks 0, 2, 10) and nonlesional (week 0) biopsies was conducted. Median infliximab half-life and peak serum concentrations over time were calculated.Infliximab immunotherapy resulted in rapid and dramatic decreases in epidermal inflammation and normalization of keratinocyte differentiation in psoriatic plaques; these changes preceded maximal clinical response. Infliximab concentrations were maintained above the detection limit (0.1 mg/mL) in the majority of patients through week 14.The clinical and immunohistologic data demonstrate a pivotal role for tumor necrosis factor-alpha in the pathogenesis of psoriasis and support further development of drugs targeting tumor necrosis factor-alpha.

Effective, rapid-acting, safe therapies are needed for the long-term treatment of psoriasis.We sought to evaluate infliximab monotherapy in maintaining clinical benefit in psoriasis.A total of 33 patients received 3 doses of 5 or 10 mg/kg of infliximab or placebo at weeks 0, 2, and 6 (double-blind phase). During the open-label phase (weeks 10-26), responding patients were evaluated for relapse (loss of at least half of the improvement in the Psoriasis Area Severity Index score at week 10) and retreated with open-label infliximab (5 or 10 mg/kg) as needed. Placebo nonresponders were treated with an induction regimen of infliximab (5 or 10 mg/kg) and followed up through week 26.In all, 29 patients received either 5 or 10 mg/kg of infliximab in the open-label extension. At week 26, psoriasis area severity index response was maintained in 40% and 73% of patients receiving 5 and 10 mg/kg of infliximab, respectively.Infliximab produced a rapid, effective, and sustainable (through week 26) effect in patients with moderate to severe psoriasis.

OKTcdr4a (IMUCLONE) is a humanized anti-CD4 IgG4 monoclonal antibody that retains the binding and in vitro immunosuppressive properties of the parent murine antibody. Psoriasis is a chronic disease for which treatment with multiple doses of monoclonal antibodies is likely to be required for adequate control.This study was performed to test the efficacy and safety of OKTcdr4a, given in sequential courses over a period of several weeks, in the treatment of moderate to severe psoriasis vulgaris.Twenty-eight patients (45.6 +/- 10.1 years of age) were studied, with a mean pretreatment Psoriasis Area and Severity Index (PASI) score of 18.3. In the first double-blind phase of the study, patients were randomized to receive OKTcdr4a as a 225 mg/course (low dose), 750 mg/course (high dose), or placebo divided into 3 identical infusions over a 5-day period. After 42 days, patients who met the criteria for re-treatment with OKTcdr4a were re-treated with the 750 mg/course in an open phase of the study.After the double-blind course of treatment, the mean PASI decreased by 11% in the placebo group, by 4% in the low-dose group, and by 17% in the high-dose group at 15 days. Twenty patients met the criteria for re-treatment (ie, did not experience a decrease in PASI score of 50% at 42 days). They were re-treated with OKTcdr4a at 43 days with the 750 mg/course in the open phase of the study. By day 99, the mean PASI score decreased from 19.9 at baseline to 17 in those patients who had received either placebo or low-dose OKTcdr4a followed by high-dose OKTcdr4a. In contrast, the mean PASI score decreased from 17.4 at baseline to only 7.7 in those patients who had received high-dose OKTcdr4a for both courses. Sustained CD4 saturation was not necessary for sustained clinical response. No patients had significant changes in circulating CD4(+) T-cell counts. The infusions were well tolerated.Targeting CD4 using sequential treatments with a humanized monoclonal antibody (OKTcdr4a) may offer another therapeutic option for the treatment of moderate to severe psoriasis.