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Background: Two phase 3 trials, POETYK PSO-1 and PSO-2, previously established the efficacy and overall safety of deucravacitinib, an oral, selective, allosteric tyrosine kinase 2 (TYK2) inhibitor, in plaque psoriasis., Objectives: To further assess the safety of deucravacitinib over 52 weeks in the pooled population from these two trials., Methods: Pooled safety data were evaluated from PSO-1 and PSO-2 in which patients with moderate-to-severe plaque psoriasis were randomized 1:2:1 to receive oral placebo, deucravacitinib or apremilast., Results: A total of 1683 patients were included in the pooled analysis. Adverse event (AE) incidence rates were similar in each treatment group, serious AEs were low and balanced across groups, and discontinuation rates were lower with deucravacitinib versus placebo or apremilast. No new safety signals emerged with longer deucravacitinib treatment. Exposure-adjusted incidence rates of AEs of interest with placebo, deucravacitinib and apremilast, respectively, were as follows: serious infections (0.8/100 person-years [PY], 1.7/100 PY, and 1.8/100 PY), major adverse cardiovascular events (1.2/100 PY, 0.3/100 PY, and 0.9/100 PY), venous thromboembolic events (0, 0.2/100 PY, and 0), malignancies (0, 1.0/100 PY and 0.9/100 PY), herpes zoster (0.4/100 PY, 0.8/100 PY, and 0), acne (0.4/100 PY, 2.9/100 PY, and 0) and folliculitis (0, 2.8/100 PY, and 0.9/100 PY). No clinically meaningful changes from baseline in mean levels, or shifts from baseline to CTCAE grade ≥3 abnormalities, were reported in laboratory parameters with deucravacitinib., Conclusions: Deucravacitinib was well-tolerated with acceptable safety over 52 weeks in patients with psoriasis., (© 2024 The Authors. Journal of the European Academy of Dermatology and Venereology published by John Wiley & Sons Ltd on behalf of European Academy of Dermatology and Venereology.)

Importance: Generalized pustular psoriasis (GPP) lacks internationally accepted definitions and diagnostic criteria, impeding timely diagnosis and treatment and hindering cross-regional clinical and epidemiological study comparisons., Objective: To develop an international consensus definition and diagnostic criteria for GPP using the modified Delphi method., Evidence Review: The rarity of GPP presents a challenge in acquiring comprehensive published clinical data necessary for developing standardized definition and criteria. Instead of relying on a literature search, 43 statements that comprehensively addressed the fundamental aspects of the definitions and diagnostic criteria for GPP were formulated based on expert reviews of 64 challenging GPP cases. These statements were presented to a panel of 33 global GPP experts for voting, discussion, and refinements in 2 virtual consensus meetings. Consensus during voting was defined as at least 80% agreement; the definition and diagnostic criteria were accepted by all panelists after voting and in-depth discussion., Findings: In the first and second modified Delphi round, 30 (91%) and 25 (76%) experts participated. In the initial Delphi round, consensus was achieved for 53% of the statements, leading to the approval of 23 statements that were utilized to develop the proposed definitions and diagnostic criteria for GPP. During the second Delphi round, the final definition established was, "Generalized Pustular Psoriasis is a systemic inflammatory disease characterized by cutaneous erythema and macroscopically visible sterile pustules." It can occur with or without systemic symptoms, other psoriasis types, and laboratory abnormalities. GPP may manifest as an acute form with widespread pustules or a subacute variant with an annular phenotype. The identified essential criterion was, "Macroscopically visible sterile pustules on erythematous base and not restricted to the acral region or within psoriatic plaques.", Conclusions and Relevance: The achievement of international consensus on the definition and diagnostic criteria for GPP underscores the importance of collaboration, innovative methodology, and expert engagement to address rare diseases. Although further validation is needed, these criteria can serve as a reference point for clinicians, researchers, and patients, which may contribute to more accurate diagnosis and improved management of GPP.

Background: Limited data exist on the characteristics of SARS-CoV-2 infections in German patients with psoriasis or psoriasis arthritis (PsA). This study analyses COVID-19 prevalence and severity of symptoms in these patients., Patients and Methods: Participants of the German registries PsoBest and CoronaBest were surveyed in February 2022. Descriptive analyses were conducted., Results: 4,818 patients were included in the analysis, mean age of 56.4 years. Positive SARS-CoV-2 tests were reported by 737 (15.3%) patients. The most frequently reported acute symptoms were fatigue (67.3%), cough (58.8%), and headache (58.3%). Longer-lasting symptoms after COVID-19 were reported by 231 of 737 patients after the acute phase. For most patients (92.9%), systemic treatment for their psoriasis or PsA was not modified during the pandemic. Patients positively tested for SARS-CoV-2 were younger on average and had more often changes in the therapy of psoriasis than negatively tested patients (8.5% vs. 5.4%)., Conclusions: In this cohort of patients with psoriasis or PsA undergoing systemic treatment, SARS-CoV-2 infections were common but less frequent than in the general German population. No risk signals for more severe COVID-19 or increased infection rates were observed in the patients. In addition, systemic treatments remained largely unchanged, so that no risks can be attributed to these therapies., (© 2024 The Authors. Journal der Deutschen Dermatologischen Gesellschaft published by Wiley‐VCH GmbH on behalf of Deutsche Dermatologische Gesellschaft.)

Aim: In the global phase 3 POETYK PSO-1 and PSO-2 trials, significantly greater proportions of deucravacitinib-treated patients met the coprimary endpoints (PASI 75, sPGA 0/1) at Week 16 versus placebo or apremilast-treated patients. This analysis evaluated onset of action and maintenance of response in patients randomized to deucravacitinib and placebo only., Methods: Adults with moderate to severe plaque psoriasis at baseline were randomized 1:2:1 to oral placebo, deucravacitinib, or apremilast. Onset of action was determined through changes from baseline in mean PASI, BSA, BSA × sPGA, and DLQI. Maintenance of response was assessed using PASI 75, PASI 90, PASI 100, sPGA 0/1, and sPGA 0 response rates through Week 52 in patients who were treated continuously with deucravacitinib, crossed over from placebo to deucravacitinib at Week 16, or received deucravacitinib and achieved PASI 75 by Week 24., Results: Deucravacitinib showed significantly higher increases in mean percent change from baseline in PASI versus placebo by Week 1. Significant improvement versus placebo was observed in all other efficacy measures by Week 8. Efficacy with deucravacitinib was maintained through Week 52., Conclusion: Deucravacitinib displayed efficacy as early as 1 week and clinical responses were maintained over 52 weeks in patients with moderate to severe plaque psoriasis.

Background: The anti-interleukin-23 antibody guselkumab (GUS) demonstrated favourable week 24 efficacy and safety over fumaric acid esters (FAE) in systemic treatment-naïve patients with moderate-to-severe plaque psoriasis (study part I)., Objectives: To compare, in study part II, the sustainability of treatment responses (weeks 24-32) in GUS- and FAE-treated patients and treatment responses (weeks 32-56) in patients treated with GUS and FAE and in FAE nonresponders switching to GUS; and, in part III, to investigate the maintenance of response through week 100 in patients withdrawn from GUS at week 56., Methods: At week 0, systemic treatment-naïve patients were randomized 1 : 1 to GUS or FAE as per label. At week 32, patients with a Psoriasis Area and Severity Index (PASI) 75 (≥ 75% improvement in PASI score) response (r) continued assigned treatment (GUSr-GUS; FAEr-FAE), whereas nonresponders (nr) received GUS (FAEnr-GUS; GUSnr-GUS). GUS-treated patients with a week 56 PASI 90 response (≥ 90% improvement in PASI score) were withdrawn (w) and followed until loss of response or week 100., Results: At week 32, 98% (n = 54/55) of GUS- and 41% (n = 14/34) of FAE-treated patients were PASI 75 responders. At week 56, 91%, 50% and 80% of GUSr-GUS, FAEr-FAE and FAEnr-GUS patients, respectively, achieved a PASI 90 response; 72%, 29% and 45%, respectively, achieved a Dermatology Life Quality Index score of 0/1. At week 100, 44 weeks postwithdrawal, 47% (n = 17/36) and 25% (n = 3/12) of GUS-GUSw and FAE-GUSw patients, respectively, maintained a PASI score ≤ 5. Overall, the adverse event and discontinuation rates were lower for GUS than FAE., Conclusions: In these exploratory analyses, GUS, as a first-line systemic treatment or second-line systemic treatment in FAE nonresponders, was associated with long-term clinical efficacy up to week 100, including a withdrawal period., Competing Interests: Conflicts of interest D.T. has received investigator honoraria, honoraria for consultancy and/or has received speakers’ honoraria and/or research grants from AbbVie, Almirall, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Galapagos, Galderma, Janssen, LEO Pharma, Lilly, MSD, Novartis, Pfizer, Regeneron/Sanofi, Samsung and UCB. C.T. has received investigator honoraria and/or has received speakers’ honoraria and/or has received grants from and/or has been an advisor for the following companies: AbbVie, Allergopharma, Almirall, Janssen, LEO Pharma and UCB. A.P. has received investigator honoraria and/or has received speakers’ honoraria and/or has received grants from and/or has been an advisor for the following companies: AbbVie, Almirall-Hermal, Amgen, Biogen Idec, Boehringer Ingelheim, Celgene, Eli Lilly, Galderma, GSK, Hexal, Janssen, LEO Pharma, Medac, Merck Serono, Mitsubishi, MSD, Novartis, Pfizer, Regeneron, Roche, Sandoz Biopharmaceuticals, Schering-Plough, Tigercat Pharma and UCB Pharma. M. Sebastian has received investigator honoraria, has received grants from and/or has been an advisor/consultant for the following companies: AbbVie, Almirall, Boehringer Ingelheim, Celgene, Dr. Reddy, Galderma, GSK, Janssen, LEO Pharma, Lilly, MSD, Mundipharma, Novartis, Regeneron and UCB Pharma. M. Sticherling has received investigator and/or speaker honoraria, has received grants from and/or has participated in clinical studies for the following companies: AbbVie, Actelion, Almirall, Amgen, Boehringer Mannheim, Celgene, Galderma, GSK, Hexal, Janssen, LEO Pharma, Lilly, MSD, Mundipharma, Novartis, Pfizer, Sandoz, Sanofi and UCB Pharma. S.G. has been an advisor for and/or has received speakers’ honoraria and/or has received grants and/or has participated in clinical trials for the following companies: AbbVie, Affibody, Akari Therapeutics, Almirall-Hermal, Amgen, Argenx, Aristea Therapeutics, Biogen Idec, Bioskin, Bristol Myers Squibb, Boehringer Ingelheim, Celgene, Dermira, Eli Lilly, Galderma, Hexal, Incyte, Janssen-Cilag, Johnson & Johnson, Klinge Pharma, Kymab, LEO Pharma, Medac, MSD, Neubourg Skin Care, Novartis, Pfizer, Pierre Fabre, Principia Biopharma, Regeneron Pharmaceuticals, Sandoz Biopharmaceuticals, Sanofi-Aventis, Trevi Therapeutics and UCB Pharma. K.S. has received investigator and/or speaker honoraria, has received grants from and/or has participated in clinical studies for the following companies: AbbVie, Almirall, Boehringer Ingelheim, Celgene, Eli Lilly, Galderma, Janssen-Cilag, LEO Pharma, Novartis, Pfizer and UCB. S.W., S.K., C.R. and H.B. are employees of Janssen-Cilag, Germany. F.T. owns Taut Science and Service, a consultancy specialized in clinical development and medical affairs, and is receiving consultancy fees from the Janssen group. K.E. has received investigator honoraria and/or has received speakers’ honoraria from and/or received grants and/or has been an advisor for the following companies: AbbVie, BMS, Boehringer Ingelheim, Janssen, Lilly, LEO Pharma, Novartis, Pfizer, Sanofi and UCB., (© The Author(s) 2023. Published by Oxford University Press on behalf of British Association of Dermatologists.)

Background: In the phase III POETYK PSO-1 and PSO-2 trials, deucravacitinib, an oral selective allosteric tyrosine kinase 2 inhibitor, was well tolerated and efficacious over 1 year in patients with psoriasis., Objective: To evaluate deucravacitinib safety and efficacy over 2 years in patients participating in the phase III trials., Methods: In the POETYK long-term extension (LTE), an ongoing phase IIIb open-label trial, adults with moderate-to-severe plaque psoriasis who completed PSO-1 or PSO-2 receive deucravacitinib 6 mg once daily. Safety was assessed via adverse events (AEs) and laboratory parameter abnormalities. Efficacy endpoints, including ≥ 75% reduction from baseline Psoriasis Area and Severity Index score (PASI 75) and static Physician's Global Assessment (sPGA) score of 0/1 (clear/almost clear), were evaluated in patients originally randomized to deucravacitinib, patients who crossed over from placebo at week 16 and patients who achieved PASI 75 at week 24 (peak efficacy)., Results: At data cutoff (1 October 2021), 1519 patients had received at least one dose of deucravacitinib; 79.0% and 39.9% had ≥ 52 weeks and ≥ 104 weeks of total deucravacitinib exposure, respectively. Exposure-adjusted incidence rates (EAIRs) per 100 person-years were similar at 1 year and 2 years for any AEs (229.2 vs. 154.4, respectively), serious AEs (5.7 vs. 6.1), discontinuations (4.4 vs. 2.8), deaths (0.2 vs. 0.4), serious infections (1.7 vs. 2.6), herpes zoster (0.9 vs. 0.8), major adverse cardiovascular events (0.3 vs. 0.4), venous thromboembolic events (0.2 vs. 0.1) and malignancies (1.0 vs. 0.9). EAIRs for COVID-19 infections were higher at 2 years than at 1 year (5.1 vs. 0.5) owing to the peak of the global COVID-19 pandemic occurring during the LTE. No clinically meaningful changes from baseline or trends were observed over 2 years in haematological, chemistry or lipid parameters. Clinical responses were maintained in patients who received continuous deu-cravacitinib treatment from baseline [PASI 75: week 52, 72.4%; week 112, 79.7%; sPGA 0/1: week 52, 57.9%; week 112, 61.1% (as observed)]. Responses at week 52 were also maintained in placebo crossovers and in week-24 PASI-75 responders., Conclusions: Deucravacitinib maintained efficacy and demonstrated consistent safety with no new safety signals observed through 2 years., Competing Interests: Conflicts of interest M.L. has received research funds on behalf of Mount Sinai from: AbbVie, Amgen, Arcutis, Avotres, Boehringer Ingelheim, Cara Therapeutics, Dermavant Sciences, Eli Lilly, Incyte, Inozyme, Janssen Research & Development, LLC, Ortho Dermatologics, Pfizer, Sanofi-Regeneron, and UCB, Inc., and is a consultant for Almirall, AltruBio Inc., AnaptysBio, Apogee, Arcutis, Inc., AstraZeneca, Atomwise, Avotres Therapeutics, Brickell Biotech, Boehringer Ingelheim, Bristol Myers Squibb, Castle Biosciences, Celltrion, CorEvitas, Dermavant Sciences, EPI, Evommune, Inc., Facilitation of International Dermatology Education, Forte Biosciences, Foundation for Research and Education in Dermatology, Galderma, Genentech, Incyte, LEO Pharma, Meiji Seika Pharma, Mindera, Pfizer, Sanofi-Regeneron, Seanergy, Strata, Takeda, Trevi, and Verrica. R.B.W. has received research grants from AbbVie, Almirall, Amgen, Celgene, Eli Lilly, Janssen, LEO Pharma, Novartis, Pfizer and UCB, and has received consulting fees from AbbVie, Almirall, Amgen, Biogen, Boehringer Ingelheim, Celgene, DICE Therapeutics, Eli Lilly, Janssen, LEO Pharma, Novartis, Pfizer, Sanofi, UCB and Union Therapeutics. H.S. has been a clinical investigator for AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, Janssen, LEO Pharma, Novartis and Sun Pharma. S.I. has received grants and personal fees from AbbVie, Eisai, GlaxoSmithKline, Janssen, Kyowa Kirin, LEO Pharma, Maruho, Sun Pharma, Taiho Yakuhin, Tanabe Mitsubishi and Torii Yakuhin, and has received personal fees from Amgen (Celgene), Boehringer Ingelheim, Bristol Myers Squibb, Daiichi Sankyo, Eli Lilly, Novartis, and UCB. C.P. has received grants from and served as a consultant for AbbVie, Almirall, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eli Lilly, Janssen, LEO Pharma, Merck, Mylan, Novartis, Pfizer, Sandoz, and UCB. J.C.S. has served on an advisory board and served as a consultant for AbbVie, LEO Pharma, Novartis, Pierre-Fabre, Sanofi Genzyme, and Trevi; has served as a speaker for AbbVie, Eli Lilly, Janssen-Cilag, LEO Pharma, Novartis and Sanofi Genzyme; and has been an investigator for AbbVie, Amgen, Bristol Myers Squibb, Galapagos, Galderma, Incyte, InfraRX, Janssen-Cilag, Manlo Therapeutics, Merck, Novartis, Pfizer, Regeneron, Trevi, and UCB. L.S. has served as a consultant, paid investigator, and/or speaker for AbbVie, Amgen, Anacor, Ascend, Astellas, AstraZeneca, Blaze Bioscience, Boehringer Ingelheim, Botanix, Bristol Myers Squibb, Celgene, Dermira, Eli Lilly, Galderma, Genentech, GlaxoSmithKline, Hexima, Janssen, LEO Pharma, Mayne Pharma, MedImmune, Merck, Merck-Serono, Novartis, Otsuka, Pfizer, Phosphagenics, Photon MD, Regeneron, Roche, Samumed, Sanofi Genzyme, Sun Pharma ANZ, Trius, UCB and Zai Lab. T.P. has served on an advisory board for and received consulting fees from AbbVie, Almirall, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eli Lilly, Galderma, Incyte, Janssen, LEO Pharma, Novartis, Pfizer, Sanofi Genzyme, Sun Pharma and UCB. E.V., A.N., R.M.K. and S.B. are employees of and shareholders in Bristol Myers Squibb. A.B. is a consultant for Bristol Myers Squibb through functional service provider Cytel. D.T. has received research support from and has been a principal investigator (clinical trials) for AbbVie, Almirall, Amgen, Biogen Idec, Boehringer Ingelheim, Eli Lilly, Galderma, GlaxoSmithKline, Janssen-Cilag, LEO Pharma, Merck Sharp & Dohme, Novartis, Pfizer, Regeneron, Roche, Sandoz-Hexal, Sanofi and UCB; has served as a consultant for AbbVie, Almirall, Galapagos, LEO Pharma, Novartis, Pfizer, and UCB; has been a lecturer for AbbVie, Almirall, Amgen, Janssen, Eli Lilly, Leo Pharma, Merck Sharp & Dohme, Novartis, Pfizer, Roche-Posay, Sandoz-Hexal, Sanofi, Target-Solution and UCB; and has served on a scientific advisory board for AbbVie, Amgen, Eli Lilly, Janssen-Cilag, LEO Pharma, Morphosis, Merck Sharp & Dohme, Novartis, Pfizer, Sanofi and UCB. A.B. has served as a speaker (received honoraria) for AbbVie, Bristol Myers Squibb, Eli Lilly and Company, Pfizer, Regeneron and Sanofi; served as a scientific adviser (received honoraria) for AbbVie, Abcentra, Aclaris, Affibody, Aligos, Almirall, Alumis, Amgen, Anaptysbio, Apogee, Arcutis, Arena, Aslan, Athenex, Bluefin Biomedicine, Boehringer Ingelheim, Bristol Myers Squibb, Cara Therapeutics, CTI BioPharma, Dermavant, EcoR1, Eli Lilly and Company, Escient, Evelo, Evommune, Forte, Galderma, HighlightII Pharma, Incyte, InnoventBio, Janssen, Landos, LEO, Lipidio, Merck, Monte Rosa Therapeutics, Nektar, Novartis, Overtone Therapeutics, Pfizer, Rani, Rapt, Regeneron, Sanofi Genzyme, Spherix Global Insights, Sun Pharma, Takeda, TLL Pharmaceutical, TrialSpark, UCB Pharma, Union, Ventyx, Vibliome and Xencor; and has acted as a clinical study investigator (institution has received clinical study funds) for AbbVie, Acelyrin, Allakos, Almirall, Alumis, Amgen, Arcutis, Athenex, Boehringer Ingelheim, Bristol Myers Squibb, Concert, Dermavant, Eli Lilly and Company, Evelo, Evommune, Galderma, Incyte, Janssen, LEO Pharma, Merck, Novartis, Pfizer, Regeneron, Sanofi, Sun Pharma, UCB Pharma and Ventyx., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Association of Dermatologists.)

Background: Scalp involvement in plaque psoriasis is challenging to treat., Objective: To evaluate the efficacy and safety of deucravacitinib (DEUC) in scalp psoriasis., Methods: POETYK PSO-1 and PSO-2 were global phase 3, 52-week, double-blinded trials in adults with moderate to severe psoriasis. Patients were randomized 1:2:1 to oral placebo, DEUC 6 mg once daily, or apremilast 30 mg twice daily. This pooled secondary analysis evaluated scalp-specific Physician Global Assessment score of 0 or 1 (0/1), ≥90% improvement from baseline in Psoriasis Scalp Severity Index, and change from baseline in Psoriasis Scalp Severity Index. Adverse events were evaluated through week 16., Results: Overall, 1084 patients with moderate to severe scalp psoriasis at baseline were included. At week 16, response rates were greater with DEUC versus placebo or apremilast for scalp-specific Physician Global Assessment 0/1 (64.0% vs 17.3% vs 37.7%; P < .0001), ≥90% improvement from baseline in Psoriasis Scalp Severity Index (50.6% vs 10.5% vs 26.1%; P < .0001), and change from baseline in Psoriasis Scalp Severity Index. Responses were maintained through 52 weeks with continuous DEUC. Safety was consistent with the entire study population., Limitations: Lack of data in milder scalp psoriasis., Conclusion: DEUC was significantly more efficacious than placebo or apremilast in improving moderate to severe scalp psoriasis and was well tolerated., Competing Interests: Conflicts of interest Dr Blauvelt has served as a speaker/received honoraria from AbbVie, Eli Lilly and Company, and UCB, served as a scientific adviser/received honoraria from AbbVie, Abcentra, Affibody, Aligos, Almirall, Alumis, Amgen, AnaptysBio, Arcutis, Arena, Aslan, Athenex, Bluefin Biomedicine, Boehringer Ingelheim, Bristol Myers Squibb, Cara Therapeutics, Dermavant, EcoR1, Eli Lilly, Escient, Evelo Biosciences, Evommune, Forte Biosciences, Galderma, HighlightII Pharma, Incyte, Janssen, Landos, Leo Pharma, Merck, Novartis, Pfizer, Rapt, Regeneron, Sanofi Genzyme, Spherix Global Insights, Sun Pharma, TLL Pharmaceutical, TrialSpark, UCB, Vibliome, and Xencor, and has acted as a clinical study investigator/institution has received clinical study funds from AbbVie, Acelyrin, Amgen, Arcutis, Athenex, Boehringer Ingelheim, Bristol Myers Squibb, Concert, Dermavant, Eli Lilly, Evelo Biosciences, Galderma, Incyte, Janssen, Leo Pharma, Merck, Novartis, Pfizer, Regeneron, Sun Pharma, and UCB. Dr Rich has conducted research as a principal investigator for AbbVie, Arcutis, Bristol Myers Squibb, Dermavant, Eli Lilly, Janssen, Novartis, Sun Pharma, and UCB. Dr Sofen has served as a clinical investigator for AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, Janssen, Leo Pharma, Novartis, and Sun Pharma. Dr Strober has served as a consultant (with honoraria) for AbbVie, Alumis, Almirall, Amgen, Arcutis, Arena, Aristea, Asana, Boehringer Ingelheim, Immunic Therapeutics, Bristol Myers Squibb, Connect Biopharma, Dermavant, Eli Lilly, EPI Health, Evelo Biosciences, Janssen, Leo Pharma, Maruho, Meiji Seika Pharma, Mindera Health, Novartis, Ono Pharmaceutical, Pfizer, Regeneron, Sanofi Genzyme, Sun Pharma, UCB, UNION Therapeutics, Ventyx Biosciences, and vTv Therapeutics; has stock options in Connect Biopharma and Mindera Health; has served as a speaker for AbbVie, Eli Lilly, Incyte, Janssen, Regeneron, and Sanofi Genzyme; served a scientific co-director (with a consulting fee) for CorEvitas Psoriasis Registry; and has served as an investigator for AbbVie, Cara Therapeutics, CorEvitas Psoriasis Registry, Dermavant, Dermira, and Novartis. Dr Merola has served as a consultant and/or investigator for Amgen, AbbVie, Biogen, Bristol Myers Squibb, Dermavant, Eli Lilly, Janssen, Leo Pharma, Novartis, Pfizer, Regeneron, Sanofi, Sun Pharma, and UCB. Dr Lebwohl has received research funds on behalf of Mount Sinai from AbbVie, Amgen, Arcutis, Avotres, Boehringer Ingelheim, Dermavant, Eli Lilly, Incyte, Janssen, Ortho Dermatologics, Regeneron, and UCB, and has served as a consultant for Aditum Bio, Almirall, AltruBio, AnaptysBio, Arcutis, Arena, Aristea, Arrive Technologies, Avotres, BiomX, Boehringer Ingelheim, Brickell Biotech, Bristol Myers Squibb, Cara Therapeutics, Castle Biosciences, CorEvitas Psoriasis Registry, Dermavant, Dr Reddy's Laboratories, Evelo Biosciences, Evommune, Forte Biosciences, Helsinn Therapeutics, Hexima, Leo Pharma, Meiji Seika Pharma, Mindera Health, Pfizer, Seanergy, and Verrica. Dr Morita has received honoraria as meeting chair/lecturer from AbbVie, AYUMI Pharmaceutical, Boehringer Ingelheim Japan, Celgene K.K., Eisai, Eli Lilly Japan K.K., Inforward, Janssen Pharmaceutical K.K., Kyowa Kirin, Maruho, Mitsubishi Tanabe Pharma, Nippon Kayaku, Novartis Pharma K.K., Taiho Pharmaceutical, Torii Pharmaceutical, and Ushio; has received funding from AbbVie GK, Eisai, Eli Lilly Japan K.K., Kyowa Hakko Kirin, Leo Pharma KK, Maruho, Mitsubishi Tanabe Pharma, Novartis Pharma K.K., Taiho Pharmaceutical, and Torii Pharmaceutical; and has received consulting fees from AbbVie GK, Boehringer Ingelheim Japan, Bristol Myers Squibb, Celgene K.K., Eli Lilly Japan K.K., GlaxoSmithKline K.K., Janssen Pharmaceutical K.K., Kyowa Kirin, Maruho, Mitsubishi Tanabe Pharma, Nichi-Iko Pharmaceutical, Nippon Kayaku, Novartis Pharma K.K., NPO Health Institute Research of Skin, Pfizer Japan, Sun Pharma, Torii Pharmaceutical, and UCB Japan. Dr Szepietowski has served as an advisory board member/consultant for AbbVie, Leo Pharma, Novartis, Pierre-Fabre, Sanofi Genzyme, and Trevi; has served as a speaker for AbbVie, Eli Lilly, Janssen-Cilag, Leo Pharma, Novartis, and Sanofi Genzyme; and has served as an investigator for AbbVie, Amgen, Bristol Myers Squibb, Galapagos, Galderma, Incyte, InfraRx, Janssen-Cilag, Menlo Therapeutics, Merck, Novartis, Pfizer, Regeneron, Trevi, and UCB. Dr Lambert has received unrestricted grants from AbbVie, Almirall, Celgene, Eli Lilly, Janssen-Cilag, Leo Pharma, Novartis, and UCB; has served as a speaker for AbbVie, Almirall, Bristol Myers Squibb, Janssen-Cilag, Pfizer, and UCB; and has served as a consultant for AbbVie, Bristol Myers Squibb, Celgene, Eli Lilly, Janssen-Cilag, Leo Pharma, Novartis, and UCB. Ms. Hippeli, Dr Colston, Dr Balagula, and Dr Banerjee are employees of and stockholders in Bristol Myers Squibb. Dr Thaçi has received grant/research support from, served as a consultant for, and served on a scientific advisory board speakers bureau for AbbVie, Almirall, Amgen, Biogen Idec, Boehringer Ingelheim, Bristol Myers Squibb, Celltrion, Eli Lilly, Galderma, Janssen-Cilag, Leo Pharma, New Bridge, Novartis, Pfizer, Regeneron, Roche, Sandoz-Hexal, Sanofi, Target-Solution, and UCB., (Copyright © 2023 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Immune-mediated inflammatory diseases (IMID) can lead to a substantial disease burden for those affected, in particular by the concomitant occurrence of other IMIDs or in the presence of comorbidities. The care of patients with IMIDs is complex and involves various medical disciplines., Objective: To describe the burden of disease and the current routine drug treatment of patients with IMID., Material and Methods: The retrospective cross-sectional analysis was based on statutory health insurance claims data from the InGef database. Prevalent patients with psoriasis (Pso), psoriatic arthritis (PsA), spondylarthritis (SpA), rheumatoid arthritis (RA), Crohn's disease (MC), ulcerative colitis (CU), or connective tissue disease were identified among 3,988,695 insured patients in 2018. The concomitant occurrence of different IMIDs and the extent to which patients with IMID are affected by other comorbidities compared to a reference population were investigated. The current routine drug treatment was described based on the use of predefined forms of treatment., Results: In the database 188,440 patients with IMID (4.7%) were identified. Compared to the reference population the prevalence of comorbidities, such as depressive episodes and cardiovascular risk factors was higher in patients with IMID. For MC, CU, RA, and PsA disease-modifying antirheumatic drugs (DMARD) and classical systemic forms of treatment were used most commonly. In Pso, SpA, and connective tissue disease nonsteroidal anti-inflammatory drugs (NSAID) were the most frequently used treatment often in combination with other drugs., Conclusion: A considerable number of patients with IMIDs (16.9-27.5%) suffer from different diseases of the IMID group. They are frequently affected by accompanying illnesses and require interdisciplinary medical treatment., (© 2022. The Author(s).)

Background: Patients with psoriasis require long-term management; therefore, understanding the long-term safety of new treatments, such as bimekizumab (BKZ), is crucial., Objectives: To evaluate BKZ's 3-year safety profile in patients with moderate-to-severe plaque psoriasis., Methods: Three years of safety data were pooled from three phase III trials (BE VIVID, BE READY and BE SURE) and their ongoing open-label extension (BE BRIGHT). Treatment-emergent adverse events (TEAEs) are reported using exposure-adjusted incidence rates (EAIRs) per 100 patient-years (PY)., Results: In total, 1495 patients received at least one BKZ dose; total BKZ exposure was 3876.4 PY. The overall EAIR of TEAEs was 175.5/100 PY and decreased with longer exposure to BKZ. The most commonly reported TEAEs were nasopharyngitis, oral candidiasis and upper respiratory tract infection (EAIRs of 15.0/100 PY, 10.1/100 PY and 6.5/100 PY, respectively); 99.3% of oral candidiasis events were mild or moderate in severity, none were serious and few led to discontinuation. EAIRs of other TEAEs of interest were low, including serious infections (1.2/100 PY), adjudicated inflammatory bowel disease (0.2/100 PY) and laboratory elevations in aspartate aminotransferase or alanine aminotransferase (> 5 × upper limit of normal: 0.6/100 PY)., Conclusions: In these analyses pooled across 3 years, no new safety signals were observed with longer exposure to BKZ. The vast majority of oral candidiasis events were mild or moderate in severity, as reported previously., (© The Author(s) 2023. Published by Oxford University Press on behalf of British Association of Dermatologists.)

Background: Cancer risk after long-term exposure to interleukin (IL)-23 inhibitors (IL-23i) and IL-17 inhibitors (IL-17i) remains to be delineated., Objective: To evaluate the risk of malignancies in patients with psoriasis treated with IL-23i and IL-17i relative to those prescribed tumour necrosis factor inhibitors (TNFi) during the first 5 years following drug initiation., Methods: A global population-based cohort study included two distinct analyses comparing patients with psoriasis under different therapeutic modalities; (i) new users of IL-17i(n = 15,331) versus TNFi (n = 15,331) and (ii) new users of IL-23i (n = 5832) versus TNFi (n = 5832)., Results: Patients prescribed IL-17i experienced a decreased risk of non-Hodgkin lymphoma (NHL; HR, 0.58; 95% CI, 0.40-0.82; p = 0.002), colorectal cancer (HR, 0.68; 95% CI, 0.49-0.95; p = 0.024), hepatobiliary cancer (HR, 0.68; 95% CI, 0.58-0.80; p < 0.001), ovary cancer (HR, 0.48; 95% CI, 0.29-0.81; p = 0.005), melanoma (HR, 0.52; 95% CI, 0.37-0.73; p < 0.001), and basal cell carcinoma (BCC; HR, 0.57; 95% CI, 0.48-0.67; p < 0.001). IL-23i was associated with a reduced risk of NHL (HR, 0.39; 95% CI, 0.19-0.78; p = 0.006), hepatobiliary cancer (HR, 0.44; 95% CI, 0.31-0.62; p < 0.001) and BCC (HR, 0.76; 95% CI, 0.57-0.99; p = 0.046). In a sensitivity analysis comparing patients managed by IL-17i and IL-23i with their biologic-naïve counterparts, these classes were associated with decreased risk of several malignancies., Conclusion: IL-17i and IL-23i are associated with decreased risk of several malignancies. These findings should be considered prior to the prescription of biologics., (© 2023 The Authors. Journal of the European Academy of Dermatology and Venereology published by John Wiley & Sons Ltd on behalf of European Academy of Dermatology and Venereology.)

Generalized pustular psoriasis (GPP) is a rare but severe skin inflammatory disorder characterized by the eruption of widespread sterile neutrophilic pustules, often accompanied by systemic inflammation. Given its life-threatening potential, GPP requires prompt accurate diagnosis and effective treatment, but its rarity and relapsing-remitting nature pose challenges in performing large-scale randomized controlled clinical trials. Established international guidelines are currently lacking and management guidance often follows that for plaque psoriasis. However, while it can co-exist with plaque psoriasis and has traditionally been classified as a most severe form of psoriasis, GPP is now recognized as a distinct entity, with its own clinicopathological, autoinflammatory, immunologic and genetic features. Research conducted over the past decade revealed that an imbalance of interleukin (IL)-36 signaling favoring the proinflammatory activity is the central driver of the pathogenesis of GPP, thereby laying the groundwork for the development of targeted therapies for the disease. This article reviews the evidence thus far on spesolimab, a selective humanized antibody against the IL-36 receptor that was recently licensed in Europe and the United States for the treatment of GPP flares in adults. In phase II, randomized controlled clinical trials, spesolimab led to rapid and effective skin clearance in patients experiencing a GPP flare and demonstrated superiority to placebo in preventing flares for up to 48 weeks with maintenance treatment, with reassuring safety and tolerability profiles. Spesolimab is considered to be a first-in-class medication establishing itself as the standard of care for the treatment of GPP flares, thus changing the paradigm of the management of GPP to a new era of scientifically- and evidence-based targeted therapy for this distinctive disease., (© 2023. The Author(s).)

Background: CT-P43 is a candidate ustekinumab biosimilar in clinical development., Objectives: This paper aims to demonstrate equivalent efficacy of CT-P43 to originator ustekinumab in adults with moderate to severe plaque psoriasis., Methods: This double-blind, phase III trial randomised patients (1:1) to receive subcutaneous CT-P43 or originator ustekinumab (45/90 mg for patients with baseline body weight ≤ 100 kg/> 100 kg) at week 0 and week 4 in Treatment Period I. Prior to week 16 dosing in Treatment Period II, patients receiving originator ustekinumab were re-randomised (1:1) to continue originator ustekinumab or switch to CT-P43; patients initially randomised to CT-P43 continued receiving CT-P43 (at weeks 16, 28 and 40). The primary endpoint of the trial was mean per cent improvement from baseline in Psoriasis Area Severity Index (PASI) score at week 12. Equivalence was concluded if confidence intervals (CIs) for the estimate of treatment difference were within pre-defined equivalence margins: ± 10% [90% CI; modified intent-to-treat set; Food and Drug Administration (FDA) approach] or ± 15% [95% CI; full analysis set for patients only receiving 45 mg doses in Treatment Period I; European Medicines Agency (EMA) approach]. Additional efficacy, pharmacokinetic, safety and immunogenicity endpoints were evaluated through week 52. Results to week 28 are reported here., Results: In Treatment Period I, 509 patients were randomised (CT-P43: N = 256; originator ustekinumab: N = 253). The mean per cent improvement in PASI score at week12 was 77.93% and 75.89% for CT-P43 and originator ustekinumab, respectively (FDA approach); per the EMA approach, corresponding values were 78.26% and 77.33%. Estimated treatment differences were 2.05 (90% CI -0.23, 4.32) and 0.94 (95% CI -2.29, 4.16); equivalence was achieved for both sets of assumptions. Further efficacy parameters and pharmacokinetic, safety and immunogenicity outcomes were comparable between treatment groups, including after switching from originator ustekinumab to CT-P43., Conclusions: CT-P43 demonstrated equivalent efficacy to originator ustekinumab in patients with moderate to severe plaque psoriasis, with comparable pharmacokinetic, safety and immunogenicity profiles., Clinical Trial Registration: ClinicalTrials.gov Identifier: NCT04673786; date of registration: 17 December, 2020., (© 2023. The Author(s).)

Background: Five-year tildrakizumab safety data have been reported as exposure-adjusted incidence rates (EAIRs) of patients with events per 100 patient-years (PYs) of exposure., Objectives: To present 5-year safety data from reSURFACE 1/2 phase 3 trials as EAIRs of events per 100 PYs of exposure, and the number needed to harm (NNH) for one adverse event of special interest (AESI) to occur., Methods: Pooled analysis from two randomized controlled trials in patients with moderate-to-severe plaque psoriasis ( n  = 1800). PSOLAR registry was used as safety reference data for NNH estimation., Results: Rates of AESI with tildrakizumab were comparable with rates reported in PSOLAR. The NNH for one-year severe infection occurrence was 412 with tildrakizumab 200 mg, and negative for tildrakizumab 100 mg due to lower rates in reSURFACE trials; the NNH for malignancy was 990 for one year with tildrakizumab 100 mg (negative for tildrakizumab 200 mg); and the NNH for major adverse cardiovascular events was 355 for one year with tildrakizumab 200 mg (negative for tildrakizumab 100 mg)., Conclusion: Tildrakizumab demonstrated a favorable safety profile over 5 years with low rates of AESI, comparable to those of the PSOLAR. Consequently, the NNH for AESI with tildrakizumab were very high or negative due to lower event rates for tildrakizumab.

Background: Spesolimab is an anti-interleukin-36 receptor monoclonal antibody approved to treat generalised pustular psoriasis (GPP) flares. We aimed to assess the efficacy and safety of spesolimab for GPP flare prevention., Methods: This multicentre, randomised, placebo-controlled, phase 2b trial was done at 60 hospitals and clinics in 20 countries. Eligible study participants were aged between 12 and 75 years with a documented history of GPP as per the European Rare and Severe Psoriasis Expert Network criteria, with a history of at least two past GPP flares, and a GPP Physician Global Assessment (GPPGA) score of 0 or 1 at screening and random assignment. Patients were randomly assigned (1:1:1:1) to receive subcutaneous placebo, subcutaneous low-dose spesolimab (300 mg loading dose followed by 150 mg every 12 weeks), subcutaneous medium-dose spesolimab (600 mg loading dose followed by 300 mg every 12 weeks), or subcutaneous high-dose spesolimab (600 mg loading dose followed by 300 mg every 4 weeks) over 48 weeks. The primary objective was to demonstrate a non-flat dose-response curve on the primary endpoint, time to first GPP flare., Findings: From June 8, 2020, to Nov 23, 2022, 157 patients were screened, of whom 123 were randomly assigned. 92 were assigned to receive spesolimab (30 high dose, 31 medium dose, and 31 low dose) and 31 to placebo. All patients were either Asian (79 [64%] of 123) or White (44 [36%]). Patient groups were similar in sex distribution (76 [62%] female and 47 [38%] male), age (mean 40·4 years, SD 15·8), and GPP Physician Global Assessment score. A non-flat dose-response relationship was established on the primary endpoint. By week 48, 35 patients had GPP flares; seven (23%) of 31 patients in the low-dose spesolimab group, nine (29%) of 31 patients in the medium-dose spesolimab group, three (10%) of 30 patients in the high-dose spesolimab group, and 16 (52%) of 31 patients in the placebo group. High-dose spesolimab was significantly superior versus placebo on the primary outcome of time to GPP flare (hazard ratio [HR]=0·16, 95% CI 0·05-0·54; p=0·0005) endpoint. HRs were 0·35 (95% CI 0·14-0·86, nominal p=0·0057) in the low-dose spesolimab group and 0·47 (0·21-1·06, p=0·027) in the medium-dose spesolimab group. We established a non-flat dose-response relationship for spesolimab compared with placebo, with statistically significant p values for each predefined model (linear p=0·0022, emax1 p=0·0024, emax2 p=0·0023, and exponential p=0·0034). Infection rates were similar across treatment arms; there were no deaths and no hypersensitivity reactions leading to discontinuation., Interpretation: High-dose spesolimab was superior to placebo in GPP flare prevention, significantly reducing the risk of a GPP flare and flare occurrence over 48 weeks. Given the chronic nature of GPP, a treatment for flare prevention is a significant shift in the clinical approach, and could ultimately lead to improvements in patient morbidity and quality of life., Funding: Boehringer Ingelheim., Competing Interests: Declaration of interests AM reports consulting fees from AbbVie, Boehringer Ingelheim, Nichi-Iko, Nippon Kayaku, and Novartis; grant support from AbbVie, Eisai, Kyowa Kirin, LEO Pharma, Maruho, Mitsubishi Tanabe, Sun Pharmaceutical Industries, Torii Pharmaceutical, and Taiho Pharmaceutical; and honoraria from AbbVie, Eli Lilly Japan, Eisai, Janssen, Kyowa Kirin, Maruho, Mitsubishi Tanabe, Novartis, Pfizer Japan, Sun Pharmaceutical Industries, Taiho Pharmaceutical, Torii Pharmaceutical, and UCB Japan; and declares advisory board participation for Bristol Myers Squibb, Eli Lilly Japan, GlaxoSmithKline, Kyowa Kirin, Pfizer Japan, and UCB Japan. BS reports consulting fees from AbbVie, Alamar, Almirall, Alumis, Amgen, Arcutis, Arena, Aristea, Asana, Bristol Myers Squibb, Boehringer Ingelheim, Connect Biopharma, Dermavant, Eli Lilly, Evelo Biosciences, Immunic Therapeutics Janssen, Kangpu Pharmaceuticals, LEO Pharma, Maruho, Meiji Seika Pharma, Mindera Health, Nimbus, Novartis, Pfizer, Protagonist, Regeneron, Sanofi-Genzyme, Sun Pharmaceutical Industries, UCB, Union Therapeutics, Ventyxbio, and vTv Therapeutics; has been a speaker for AbbVie, Arcutis, Dermavant, Eli Lilly, Incyte, Janssen, Regeneron, and Sanofi-Genzyme; is a scientific co-director (receiving a consulting fee) for the CorEvitas Psoriasis Registry; is an investigator for the CorEvitas Psoriasis Registry; has stock options in Connect Biopharma and Mindera Health; and is the editor-in-chief (receiving an honorarium) of the Journal of Psoriasis and Psoriatic Arthritis. ADB reports consulting fees from AbbVie, Boehringer Ingelheim, Bristol Myers Squibb, and UCB; honoraria from Almirall and Boehringer Ingelheim; and grant support from Boehringer Ingelheim, Bristol Myers Squibb, and Novartis. SEC reports consulting fees from AbbVie, Boehringer Ingelheim, Eli Lilly, Janssen, and Novartis; honoraria from AbbVie, Boehringer Ingelheim, Janssen, and Novartis; meeting attendance support from AbbVie, Boehringer Ingelheim, and Novartis; and leadership or fiduciary roles for the International Psoriasis Council and Malaysian Skin Foundation. MJA reports consulting fees from Boehringer Ingelheim, Eli Lilly, Innovaderm, and UCB; and a leadership or fiduciary role for the Association of Professors in Dermatology. SM declares no competing interests. T-FT reports consulting fees from AbbVie, Boehringer Ingelheim, Bristol Myers Squibb, Pfizer, and Sanofi; honoraria from AbbVie, Boehringer Ingelheim, Eli Lilly, Janssen, Pfizer, and UCB; meeting attendance support from Pfizer; and declares advisory board participation for AbbVie, Boehringer Ingelheim, Eli Lilly, and Pfizer. KBG reports grant support from AbbVie, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, and UCB; and consulting fees from AbbVie, Almirall, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Dermavant, Eli Lilly, Janssen, LEO Pharma, Moonlake, Novartis, Pfizer, Protagonist, and UCB. DT reports grant support from LEO Pharma and Novartis; consulting fees, honoraria, or advisory board participation from AbbVie, Boehringer Ingelheim, Eli Lilly, Janssen-Cilag, Novartis, and Pfizer; and a leadership or fiduciary role for the German Psoriasis Patients Association. MZ reports consulting fees from AbbVie, Boehringer Ingelheim, Bristol Myers Squibb, LEO Pharma China, Novartis, Pfizer, and Xian-Janssen. NH, TH, and CT are employees of Boehringer Ingelheim. MGL is an employee of Mount Sinai and has received research funds from AbbVie, Amgen, Arcutis, Avotres, Boehringer Ingelheim, Cara Therapeutics, Dermavant Sciences, Eli Lilly, LEO Pharma, Incyte, Janssen Research & Development, Ortho Dermatologics, Pfizer, Regeneron, and UCB; and is a consultant for Aditum Bio, Allergan, Almirall, AltruBio, AnaptysBio, Arcutis, Aristea Therapeutics, Avotres Therapeutics, BirchBioMed, BMD Skincare, Boehringer Ingelheim, Brickell Biotech, Bristol Myers Squibb, Cara Therapeutics, Castle Biosciences, Celltrion, CorEvitas, Dermavant Sciences, Dr Reddy, EMD Serono, EPI, Evelo Biosciences, Evommune, Facilitation of International Dermatology Education, Forte Biosciences, Foundation for Research and Education in Dermatology, Galderma, Genentech, Helsinn, Incyte, Inozyme Pharma, Kyowa Kirin, LEO Pharma, Meiji Seika Pharma, Menlo, Mindera, Mitsubishi, Neuroderm, Pfizer, Seanergy, Strata, Theravance, Trevi, and Verrica., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: Bimekizumab is a monoclonal IgG1 antibody that inhibits interleukin-17A/F. Bimekizumab is more efficacious than secukinumab over 1 year in the treatment of psoriasis., Objective: Evaluate the safety and efficacy of bimekizumab through 2 years in patients with moderate to severe plaque psoriasis., Methods: The BE RADIANT phase 3b randomized controlled trial consisted of a 48-week double-blinded period, where patients received bimekizumab (320 mg every 4 or 8 weeks) or secukinumab (300 mg weekly to Week 4, then every 4 weeks), and an open-label extension (OLE). From Week 48, all patients received bimekizumab in the OLE., Results: At Week 48, more patients achieved complete skin clearance (PASI 100; modified non-responder imputation) with bimekizumab than secukinumab (74.8% vs 52.8%). PASI 100 responses were maintained to Week 96 in continuous bimekizumab patients (70.8%); patients who switched from secukinumab to bimekizumab had increased rates at Week 96 (76.6%). The most common adverse events were: nasopharyngitis, oral candidiasis, and urinary tract infection. Safety data were consistent with the known safety profile of bimekizumab., Limitations: Limited racial diversity; overlap with the COVID-19 pandemic., Conclusions: High PASI 100 responses achieved with bimekizumab over 48 weeks were sustained through Week 96; secukinumab patients who switched to bimekizumab achieved similar responses by Week 96., Competing Interests: Conflicts of interest Dr Strober is a consultant (honoraria) for AbbVie, Alumis, Almirall, Amgen, Arcutis, Arena, Aristea, Asana, Boehringer Ingelheim, Bristol-Myers-Squibb, Connect Biopharma, Dermavant, Eli Lilly, EPI Health, Evelo Biosciences, Immunic Therapeutics, Janssen, LEO Pharma Maruho, Meiji Seika Pharma, Mindera Health, Novartis, Ono, Pfizer, Regeneron, Sanofi-Genzyme, Sun Pharma, UCB Pharma, Union Therapeutics, Ventyxbio, vTv Therapeutics; has stock options from Connect Biopharma and Mindera Health; is a speaker for AbbVie, Eli Lilly, Incyte, Janssen, Regeneron, Sanofi-Genzyme; is a scientific codirector (consulting fee) for CorEvitas (formerly Corrona) Psoriasis Registry; is an investigator for AbbVie, Cara, CorEvitas Psoriasis Registry, Dermavant, Dermira, and Novartis; and serves as editor-in-chief (honorarium) of Journal of Psoriasis and Psoriatic Arthritis. Dr Paul receives consulting fees and/or grants from AbbVie, Almirall, Amgen, Aslan, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Galderma, GSK, Janssen, LEO Pharma, Eli Lilly, Mylan, Novartis, Pierre Fabre, Pfizer, Sanofi Regeneron, and UCB Pharma. Dr Blauvelt has served as a speaker (received honoraria) for AbbVie, Arcutis, Bristol Myers Squibb, Eli Lilly, Pfizer, Regeneron, Sanofi, and UCB Pharma; served as a scientific adviser (received honoraria) for AbbVie, Abcentra, Affibody, Aligos, Almirall, Alumis, Amgen, Anaptysbio, Arcutis, Arena, Aslan, Athenex, Bluefin Biomedicine, Boehringer Ingelheim, Bristol Myers Squibb, Cara Therapeutics, Dermavant, EcoR1, Eli Lilly, Escient, Evelo, Evommune, Forte, Galderma, HighlightII Pharma, Incyte, InnoventBio, Janssen, Landos, LEO Pharma, Merck, Novartis, Pfizer, Rapt, Regeneron, Sanofi Genzyme, Spherix Global Insights, Sun Pharma, TLL Pharmaceutical, TrialSpark, UCB Pharma, Vibliome, and Xencor; and has served as a clinical study investigator (institution has received clinical study funds) for AbbVie, Acelyrin, Almirall, Amgen, Arcutis, Athenex, Boehringer Ingelheim, Bristol Myers Squibb, Concert, Dermavant, Eli Lilly, Evelo, Evommune, Galderma, Incyte, Janssen, LEO Pharma, Merck, Novartis, Pfizer, Regeneron, Sun Pharma, and UCB Pharma. Dr Thaçi receives honoraria for participation on advisory boards; as a speaker and for consultancy from AbbVie, Almirall, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, Galapagos, Janssen, LEO Pharma, Morphosis, Novartis, Pfizer, Regeneron, Samsung, Sandoz, Sanofi Genzyme, and UCB Pharma; and has research grants received from LEO Pharma and Novartis. Dr Puig received consultancy/speaker’s honoraria from and/or participated in trials sponsored by AbbVie, Almirall, Amgen, Baxalta, Biogen, Boehringer Ingelheim, Celgene, Eli Lilly, Gebro, Janssen, JS BIOCAD, LEO Pharma, Merck-Serono, MSD, Mylan, Novartis, Pfizer, Regeneron, Roche, Samsung-Bioepis, Sandoz, Sanofi Genzyme, and UCB Pharma. Dr Lebwohl is an employee of Mount Sinai; receives research funds from AbbVie, Amgen, Arcutis, Avotres, Boehringer Ingelheim, Dermavant, Eli Lilly, Incyte, Janssen, LLC, Ortho Dermatologics, Regeneron, and UCB Pharma; and is a consultant for Aditum Bio, Almirall, AltruBio Inc, AnaptysBio, Arcutis, Inc, Aristea Therapeutics, Arrive Technologies, Avotres Therapeutics, BiomX, Boehringer Ingelheim, Bristol Myers Squibb, Cara Therapeutics, Castle Biosciences, Corrona, Dermavant, Dr. Reddy’s Laboratories, Evelo Biosciences, Evommune, Inc, Facilitation of International Dermatology Education, Forte Biosciences, Foundation for Research and Education in Dermatology, Helsinn Therapeutics, Hexima Ltd, LEO Pharma, Meiji Seika Pharma, Mindera, Pfizer, Seanergy, and Verrica. Ms White, Ms Vanvoorden, and Ms Deherder are employees and shareholders of UCB Pharma. Dr Gomez is a former employee and shareholder of UCB Pharma. Dr Eyerich is a speaker and/or advisor for AbbVie, Almirall, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, Janssen, LEO Pharma, Pfizer, Novartis, Sanofi and UCB Pharma., (Copyright © 2023 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

What Is This Summary About?: This is a summary of a paper published in a medical journal that describes the results of a study called POETYK PSO-1, which looked at a new treatment called deucravacitinib for plaque psoriasis. Plaque psoriasis appears on the body as round or oval raised patches (called plaques) typically covered by scales. This can cause the skin to itch, crack or bleed, and the associated itching and pain can make it difficult to perform basic everyday tasks. Living with psoriasis can cause emotional distress. Treatments are available, but some do not always reduce the symptoms of psoriasis, some may need to be injected or taken multiple times a day, and some may have side effects. Researchers are looking for new treatments that are more effective, convenient to take, and have acceptable safety and tolerability., What Happened in the Study?: Deucravacitinib is a once-daily pill taken by mouth (orally) that was studied as a treatment for moderate to severe plaque psoriasis in adults in two large studies conducted globally, PSO-1 and PSO-2. The POETYK PSO-1 study compared deucravacitinib with placebo (an inactive pill designed to have no effect) and an approved psoriasis treatment called apremilast, which is a pill taken twice a day. These were tested in adults with moderate to severe plaque psoriasis, which involved 10% or more of their body (equal to 10 or more handprints). The aim of the study was to compare the ability of deucravacitinib with placebo or apremilast to improve psoriasis for the people in the study, and to compare side effects that people had., What Do the Results of the Poetyk Pso-1 Study Show?: After 4 months of treatment, more people taking deucravacitinib had improvements in psoriasis plaques and skin appearance than those taking placebo or apremilast. The study also showed that people continued to see these improvements after taking deucravacitinib for up to 1 year. Side effects are events that happened during the study treatment phase that may or may not be caused by that treatment. Side effects for people taking deucravacitinib were generally mild and occurred in similar numbers overall to those in people taking placebo. The most common side effects in people taking deucravacitinib were inflammation or infection of the nasal (nose) passages and throat. Clinical Trial Registration: NCT03624127 (POETYK PSO-1 study) (ClinicalTrials.gov).

What Is This Summary About?: This is a summary of a paper published in a medical journal that describes the results of a study called POETYK PSO-2, which investigated a new treatment for plaque psoriasis. Plaque psoriasis appears on the body as dry, discolored, patches of skin that can be flaky and covered in scales. This can make the skin itch, crack or bleed and make it difficult for people with psoriasis to perform basic everyday tasks. Treatments are available, but some do not always reduce symptoms or may need to be injected or taken multiple times a day, which can be difficult to do, or can have undesirable side effects. Researchers are looking for new treatments for psoriasis., What Happened in the Study?: Deucravacitinib is a once-daily pill taken by mouth (orally) that was studied as a treatment for moderate to severe plaque psoriasis in two large studies conducted globally, PSO-1 and PSO-2. POETYK PSO-2 was a Phase 3 research study, which is a study that tests a treatment in a large group of participants, that looked at how well deucravacitinib worked in participants with moderate to severe plaque psoriasis compared to a placebo (an inactive pill that has no effect) and an approved psoriasis treatment called apremilast, which is a pill taken twice a day. These medications were tested in adults with moderate to severe plaque psoriasis, which is psoriasis involving 10% or more of their body (equal to 10 or more handprints). The aims of the POETYK PSO-2 study were to find out if treatment with deucravacitinib could improve psoriasis for the participants in the study and to see if there were any side effects. Side effects are events that happened during treatment that may or may not be caused by that treatment. The study also wanted to find out what would happen after stopping treatment with deucravacitinib in participants who had shown major improvements in their psoriasis., What Do the Results of the Poetyk Pso-2 Study Show?: After 4 months of treatment, more participants taking deucravacitinib had significantly greater improvements in psoriasis than those taking placebo or apremilast. The study also showed that participants continued to see these improvements after taking deucravacitinib for up to 1 year. Some participants maintained the improvements in their psoriasis with deucravacitinib after stopping treatment and switching to a placebo. Side effects for participants taking deucravacitinib were generally mild and occurred in similar numbers to those in participants taking placebo. The most common side effects in participants taking deucravacitinib were inflammation of the nose and throat (a common cold) which occurred at a similar rate in participants who took placebo. Clinical Trial Registration: NCT03611751 (POETYK PSO-2 study) (ClinicalTrials.gov).

Competing Interests: Conflicts of interest See Appendix 1 in the Supporting Information for the full list.

Background: Guselkumab has demonstrated favourable safety and efficacy across individual clinical studies in adults with moderate-to-severe plaque psoriasis., Objectives: To evaluate the safety of guselkumab in patients with psoriasis using pooled data from seven phase II/III studies (X-PLORE, VOYAGE 1, VOYAGE 2, NAVIGATE, ORION, ECLIPSE, Japan registration)., Methods: All studies, except NAVIGATE and ECLIPSE (active comparator-controlled only), included a 16-week placebo-controlled period; X-PLORE, VOYAGE 1 and VOYAGE 2 included both placebo and active controls. In most studies, guselkumab-treated patients received 100-mg subcutaneous injections at week 0, week 4, and then every 8 weeks thereafter. Safety data were summarized for the placebo-controlled period (weeks 0-16) and through the end of the reporting period (up to 5 years). Incidence rates of key safety events were integrated post hoc, adjusted for the duration of follow-up and reported per 100 patient-years (PY)., Results: During the placebo-controlled period, 544 patients received placebo (165 PY) and 1220 received guselkumab (378 PY). Through the end of the reporting period, 2891 guselkumab-treated patients contributed 8662 PY of follow-up. During the placebo-controlled period, in the guselkumab and placebo groups, respectively, rates of adverse events (AEs) were 346/100 PY and 341/100 PY, and infections were 95.9/100 PY and 83.6/100 PY. Rates of serious AEs (6.3/100 PY vs. 6.7/100 PY), AEs leading to discontinuation (5.0/100 PY vs. 9.7/100 PY), serious infections (1.1/100 PY vs. 1.2/100 PY), malignancy (0.5 patients/100 PY vs. 0.0 patients/100 PY) and major adverse cardiovascular events (MACE; 0.3/100 PY vs. 0.0/100 PY) were low and comparable between guselkumab and placebo. Through the end of the reporting period, safety event rates were lower than or comparable to the placebo-controlled period in guselkumab-treated patients: AEs, 169/100 PY; infections, 65.9/100 PY; serious AEs, 5.3/100 PY; AEs leading to discontinuation, 1.6/100 PY; serious infections, 0.9/100 PY; malignancy, 0.7/100 PY; and MACE, 0.3/100 PY. There were no cases of Crohn disease, ulcerative colitis, opportunistic infection or active tuberculosis related to guselkumab., Conclusions: In this comprehensive analysis of 2891 guselkumab-treated patients with psoriasis followed for up to 5 years (8662 PY), guselkumab demonstrated favourable safety, consistent with previous reports. Safety event rates in guselkumab-treated patients were similar to those observed with placebo and were consistent throughout long-term treatment., Competing Interests: Conflicts of interest M.G.L. is an employee of Mount Sinai and receives research funds from AbbVie, Amgen, Arcutis, Avotres, Boehringer Ingelheim, Cara Therapeutics, Dermavant Sciences, Eli Lilly, Incyte, Janssen Research & Development, Ortho Dermatologics, Regeneron and UCB; and is a consultant for Aditum Bio, Almirall, AltruBio, AnaptysBio, Arcutis, Aristea Therapeutics, Avotres Therapeutics, Brickell Biotech, Boehringer Ingelheim, Bristol Myers Squibb, Cara Therapeutics, Castle Biosciences, Celtrion, CorEvitas, Dermavant Sciences, Dr. Reddy, EPI, Evommune, Facilitation of International Dermatology Education, Forte Biosciences, Foundation for Research and Education in Dermatology, Helsinn, Hexima, Incyte, LEO Pharma, Meiji Seika Pharma, Mindera, Pfizer, Seanergy, Strata, Trevi and Verrica. J.F.M. is a consultant and/or investigator for AbbVie, Amgen, Biogen, Bristol Myers Squibb, Dermavant, Eli Lilly, Incyte, Janssen, LEO Pharma, Novartis, Pfizer, Regeneron, Sanofi, Sun Pharma and UCB. K.R. and D.C. are employees of Janssen Scientific Affairs; employees own stock in Johnson & Johnson, of which Janssen is a subsidiary. M.M., J.Y. and Y.Y. are employees of Janssen Research & Development; employees own stock in Johnson & Johnson, of which Janssen is a subsidiary. Y.-W.Y. is an employee of Immunology Global Medical Affairs, Janssen Pharmaceutical Companies of Johnson & Johnson; employees own stock in Johnson & Johnson, of which Janssen is a subsidiary. D.T. has received honoraria for participation on advisory boards, as a speaker and for consultancy from AbbVie, Almirall, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, Galapagos, Galderma, Janssen, Kyowa Hakko Kirin, LEO Pharma, Merck Sharp & Dohme, Morphosys, Novartis, Pfizer, Regeneron, Sandoz-Hexal, Sanofi, Sun Pharma and UCB; and has received research grants from LEO Pharma and Novartis. R.G.L. has served and received compensation in the form of grant funding and/or honoraria as principal investigator; and is on the scientific advisory board or has served as a speaker for AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eli Lilly, Janssen, LEO Pharma, Merck, Novartis, Pfizer, Sun Pharma and UCB Pharma., (© The Author(s) 2023. Published by Oxford University Press on behalf of British Association of Dermatologists.)

Background: BE SURE 1-year results demonstrated the superior efficacy of bimekizumab compared with adalimumab with no unexpected safety findings., Objectives: To provide efficacy and safety data over 2 years of bimekizumab treatment compared with adalimumab from BE SURE and the BE BRIGHT open-label extension (OLE) in patients with moderate-to-severe plaque psoriasis., Methods: The 56-week double-blinded BE SURE phase III randomized controlled trial randomized patients 1 : 1 : 1 to bimekizumab 320 mg every 4 weeks (Q4W), bimekizumab 320 mg Q4W to week 16 then every 8 weeks (Q8W), or adalimumab 40 mg every 2 weeks to week 24 then bimekizumab 320 mg Q4W. After completing BE SURE, patients could enter the ongoing BE BRIGHT OLE, with possible dosing adjustments based on Psoriasis Area and Severity Index (PASI). The primary outcome in BE BRIGHT was incidence of treatment-emergent adverse events (TEAEs); safety data are reported by study period through week 104. Efficacy data are reported for the intention-to-treat population through week 104 by initial randomization group, with ≥ 90% improvement from baseline PASI (PASI 90) and 100% improvement (PASI 100) as key outcomes., Results: Of the patients randomized to bimekizumab, 158 were assigned to Q4W, and 161 to Q4W/Q8W. At week 104, PASI 90 was achieved by 91.2% and 89.7%, and PASI 100 was achieved by 72.3% and 68.1%, for Q4W and Q4W/Q8W, respectively; comparable to week 16 results. Among the 159 patients randomized to adalimumab, responses rapidly and substantially increased after the week 24 bimekizumab switch; at week 104, 96.9% and 70.2% of patients achieved PASI 90 and PASI 100 respectively. Through weeks 24-104, the three most common TEAEs in any bimekizumab-treated group were nasopharyngitis, oral candidiasis and upper respiratory tract infection. Rates of serious TEAEs were low., Conclusions: Clinical responses observed through week 16 of BE SURE in patients randomized to bimekizumab were sustained through 104 weeks of treatment, regardless of Q4W or Q8W maintenance dosing. Response rates were also sustained through week 104 in patients who switched from adalimumab to bimekizumab at week 24, and were similar to those observed in the bimekizumab groups. Bimekizumab was well tolerated with no new safety signals., Competing Interests: Conflicts of interest: See Appendix., (© The Author(s) 2022. Published by Oxford University Press on behalf of British Association of Dermatologists.)

Background: Effective, well-tolerated oral psoriasis treatments are needed., Objective: To compare the efficacy and safety of deucravacitinib, an oral, selective, allosteric tyrosine kinase 2 inhibitor, versus placebo and apremilast in adults with moderate to severe plaque psoriasis., Methods: Participants were randomized 2:1:1 to deucravacitinib 6 mg every day (n = 332), placebo (n = 166), or apremilast 30 mg twice a day (n = 168) in the 52-week, double-blinded, phase 3 POETYK PSO-1 trial (NCT03624127). Coprimary end points included response rates for ≥75% reduction from baseline in Psoriasis Area and Severity Index (PASI 75) and static Physician's Global Assessment score of 0 or 1 (sPGA 0/1) with deucravacitinib versus placebo at week 16., Results: At week 16, response rates were significantly higher with deucravacitinib versus placebo or apremilast for PASI 75 (194 [58.4%] vs 21 [12.7%] vs 59 [35.1%]; P < .0001) and sPGA 0/1 (178 [53.6%] vs 12 [7.2%] vs 54 [32.1%]; P < .0001). Efficacy improved beyond week 16 and was maintained through week 52. Adverse event rates with deucravacitinib were similar to those with placebo and apremilast., Limitations: One-year duration, limited racial diversity., Conclusion: Deucravacitinib was superior to placebo and apremilast across multiple efficacy end points and was well tolerated in moderate to severe plaque psoriasis., Competing Interests: Conflicts of interest Dr Armstrong has received research grants and personal fees from Bristol Myers Squibb, Eli Lilly, Janssen, Leo Pharma, and Novartis; has received personal fees from Boehringer Ingelheim/Parexel, Celgene, Dermavant, Genentech, GlaxoSmithKline, Menlo Therapeutics, Merck, Modernizing Medicine, Ortho Dermatologics, Pfizer, Regeneron, Sanofi Genzyme, Science 37, Sun Pharma, and Valeant; and has received grants from Dermira, Kyowa Hakko Kirin, and UCB, outside the submitted work. Dr Gooderham has served on an advisory board and as a principal investigator for, and has received lecture fees from, AbbVie, Galderma, Leo Pharma, Pfizer, and Regeneron; has served on an advisory board for, and has received lecture fees from, Actelion; has served as a principal investigator for, and received consulting fees from, Akros Pharma; has served on an advisory board and as a principal investigator for, and received lecture and consulting fees from, Amgen, Boehringer Ingelheim, Celgene, Eli Lilly, Janssen, Novartis, Sanofi Genzyme, and Valeant; has served as a principal investigator for Arcutis, Bristol Myers Squibb, Dermira, GlaxoSmithKline, MedImmune, Merck, Roche Laboratories, and UCB; and has served as a principal investigator for, and received lecture fees from, Glenmark. Dr Warren has received research grants from AbbVie, Almirall, Amgen, Celgene, Eli Lilly, Janssen, Leo Pharma, Novartis, Pfizer, and UCB and has received consulting fees from AbbVie, Almirall, Amgen, Biogen, Boehringer Ingelheim, Celgene, Eli Lilly, Janssen, Leo Pharma, Novartis, Pfizer, Sanofi, UCB, and UNION. Dr Papp has served on a speakers bureau for AbbVie, Amgen, Astellas, Celgene, Eli Lilly, Galderma, Janssen, Kyowa Hakko Kirin, Leo Pharma, Merck Sharp & Dohme, Novartis, Pfizer, and Valeant; has received grant/research support from AbbVie, Akros, Allergan, Amgen, Anacor, Arcutis, AstraZeneca, Baxalta, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Coherus, Dermira, Dow Pharma, Eli Lilly, Galderma, Genentech, GlaxoSmithKline, Janssen, Kyowa Hakko Kirin, Leo Pharma, MedImmune, Meiji Seika Pharma, Merck Serono, Novartis, Pfizer, Regeneron, Roche, Sanofi Genzyme, Takeda, UCB, and Valeant; has served as a consultant for AbbVie, Akros, Amgen, Arcutis, Astellas, AstraZeneca, Baxalta, Baxter, Boehringer Ingelheim, Bristol Myers Squibb, CanFite, Celgene, Coherus, Dermira, Dow Pharma, Eli Lilly, Forward Pharma, Galderma, Genentech, Janssen, Kyowa Hakko Kirin, Leo Pharma, Meiji Seika Pharma, Merck Serono, Merck Sharp & Dohme, Mitsubishi Pharma, Novartis, Pfizer, Regeneron, Roche, Sanofi Genzyme, Takeda, UCB, and Valeant; has received honoraria from AbbVie, Akros, Amgen, Baxter, Boehringer Ingelheim, Celgene, Coherus, Eli Lilly, Forward Pharma, Galderma, GlaxoSmithKline, Janssen, Kyowa Hakko Kirin, Merck Serono, Merck Sharp & Dohme, Novartis, Pfizer, Takeda, UCB, and Valeant; and has served as a scientific officer, on a steering committee, and on an advisory board for AbbVie, Akros, Amgen, Anacor, Astellas, Baxter, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Dow Pharma, Eli Lilly, Galderma, Janssen, Kyowa Hakko Kirin, Merck Serono, Merck Sharp & Dohme, Novartis, Pfizer, Regeneron, Sanofi Genzyme, and Valeant. Dr Strober has served as a consultant (honoraria) for AbbVie, Almirall, Amgen, Arcutis, Arena, Aristea, Asana, Boehringer Ingelheim, Bristol Myers Squibb, Connect Biopharma, Dermavant, Equillium, GlaxoSmithKline, Immunic Therapeutics, Janssen, Leo Pharma, Eli Lilly, Maruho, Meiji Seika Pharma, Mindera, Novartis, Ortho Dermatologics, Pfizer, Regeneron, Sanofi Genzyme, Sun Pharma, UCB, Ventyxbio, and vTv Therapeutics; has served as a speaker for AbbVie, Eli Lilly, Janssen, and Sanofi Genzyme; has served as coscientific director for, and received consulting fees from, CorEvitas' (Corrona) Psoriasis Registry; and has served as an investigator for AbbVie, Cara, CorEvitas' (Corrona) Psoriasis Registry, Dermavant, Dermira, and Novartis. Dr Thaçi has received grant/research support from, and served on a scientific advisory board member and a speaker's bureau for, AbbVie, Almirall, Amgen, Biogen Idec, Boehringer Ingelheim, Eli Lilly, Galapagos, Galderma, Janssen-Cilag, Leo Pharma, Novartis, Pfizer, Regeneron, Roche, Sandoz-Hexal, Sanofi, Target-Solution, and UCB. Dr Morita has received honoraria as a meeting chair or lecturer from AbbVie, AYUMI, Boehringer Ingelheim Japan, Celgene K.K., Eisai, Eli Lilly Japan K.K., Inforward, Janssen Pharmaceutical K.K., Kyowa Kirin, Maruho Co., Mitsubishi Tanabe Pharma, Nippon Kayaku, Novartis Pharma K.K., Taiho Pharmaceutical, Torii Pharmaceutical, and Ushio; has received funding from AbbVie GK, Eisai, Eli Lilly Japan K.K., Kyowa Hakko Kirin, Leo Pharma K.K., Maruho, Mitsubishi Tanabe Pharma, Novartis Pharma K.K., Taiho Pharmaceutical, and Torii Pharmaceutical; has received consulting fees from AbbVie, Boehringer Ingelheim Japan, Bristol Myers Squibb, Celgene K.K., Eli Lilly Japan K.K., GlaxoSmithKline K.K., Janssen Pharmaceutical K.K., Kyowa Hakko Kirin, Maruho, Mitsubishi Tanabe Pharma, Nichi-Iko Pharmaceutical, Nippon Kayaku, Novartis Pharma K.K., NPO Health Institute Research of Skin, Pfizer Japan, Sun Pharma, Taiho Pharmaceutical, and UCB Japan. Dr Szepietowski has served as an advisory board member/consultant for AbbVie, Leo Pharma, Novartis, Pierre-Fabre, Sanofi Genzyme, and Trevi; has served as a speaker for AbbVie, Eli Lilly, Janssen-Cilag, Leo Pharma, Novartis, and Sanofi Genzyme; and has served as an investigator for AbbVie, Amgen, Bristol Myers Squibb, Galapagos, Galderma, Incyte, InfraRX, Janssen-Cilag, Menlo Therapeutics, Merck, Novartis, Pfizer, Regeneron, UCB, and Trevi. Dr Imafuku has received grants and personal fees from AbbVie, Eisai, Janssen, Kyowa Kirin, Leo Pharma, Maruho, Sun Pharma, Taiho Yakuhin, Tanabe Mitsubishi, and Torii Yakuhin and has received personal fees from Amgen (Celgene), Bristol Myers Squibb, Daiichi Sankyo, Eli Lilly, Novartis, and UCB. Dr Colston, Ms Linaberry, and Dr Banerjee are employees of and shareholders in Bristol Myers Squibb. Dr Throup, Dr Kundu, and Dr Schoenfeld were employees of and shareholders in Bristol Myers Squibb at the time of study conduct. Dr Blauvelt has served as a speaker/received honoraria from AbbVie and UCB; served as a scientific adviser/received honoraria from AbbVie, Abcentra, Affibody, Aligos, Almirall, Alumis, Amgen, AnaptysBio, Arcutis, Arena, Aslan, Athenex, Boehringer Ingelheim, Bristol Myers Squibb, Cara Therapeutics, Dermavant, EcoR1, Eli Lilly and Company, Evelo, Evommune, Forte Biosciences, Galderma, HighlightII Pharma, Incyte, Janssen, Landos, Leo Pharma, Merck, Novartis, Pfizer, Rapt, Regeneron, Sanofi Genzyme, Spherix Global Insights, Sun Pharma, TLL Pharmaceutical, TrialSpark, UCB, Vibliome, and Xencor; and has acted as a clinical study investigator for (institution has received clinical study funds from) AbbVie, Acelyrin, Amgen, Arcutis, Athenex, Boehringer Ingelheim, Bristol Myers Squibb, Dermavant, Eli Lilly and Company, Evelo, Galderma, Incyte, Janssen, Leo, Merck, Novartis, Pfizer, Regeneron, Sun Pharma, and UCB., (Copyright © 2022 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Deucravacitinib, an oral, selective, allosteric tyrosine kinase 2 inhibitor, inhibits cytokine signaling in psoriasis pathogenesis., Objective: The objective of this study was to demonstrate deucravacitinib superiority versus placebo and apremilast in moderate to severe plaque psoriasis based on ≥75% reduction from baseline in Psoriasis Area and Severity Index and a static Physician's Global Assessment score of 0 (clear) or 1 (almost clear) with a ≥2-point improvement from baseline at week 16., Methods: POETYK psoriasis second trial (NCT03611751), a 52-week, double-blinded, phase 3 trial, randomized patients 2:1:1 to deucravacitinib 6 mg every day (n = 511), placebo (n = 255), or apremilast 30 mg twice a day (n = 254)., Results: At week 16, significantly more deucravacitinib-treated patients versus placebo and apremilast patients achieved ≥75% reduction from baseline in Psoriasis Area and Severity Index (53.0% vs 9.4% and 39.8%; P < .0001 vs placebo; P = .0004 vs apremilast) and static Physician's Global Assessment score of 0 or 1 (49.5% vs 8.6% and 33.9%; P < .0001 for both). Efficacy was maintained until week 52 with continuous deucravacitinib. The most frequent adverse event with deucravacitinib was nasopharyngitis. Serious adverse events and discontinuations due to adverse events were infrequent. No clinically meaningful changes were observed in laboratory parameters., Limitations: The study duration was 1 year., Conclusion: Deucravacitinib demonstrated superiority versus placebo and apremilast and was well tolerated in adults with moderate to severe plaque psoriasis., Competing Interests: Conflicts of interest Dr Strober has served as a consultant (honoraria) for AbbVie, Almirall, Amgen, Arcutis, Arena, Aristea, Asana, Boehringer Ingelheim, Bristol Myers Squibb, Connect Biopharma, Dermavant, Eli Lilly, Equillium, GlaxoSmithKline, Immunic Therapeutics, Janssen, Leo Pharma, Maruho, Meiji Seika Pharma, Mindera, Novartis, Ortho Dermatologics, Pfizer, Regeneron, Sanofi Genzyme, Sun Pharma, UCB, Ventyxbio, and vTv Therapeutics; has served as a speaker for AbbVie, Eli Lilly, Janssen, and Sanofi Genzyme; has served as a coscientific director (consulting fee) for CorEvitas' (Corrona) Psoriasis Registry; and has served as an investigator for AbbVie, Cara, CorEvitas' (Corrona) Psoriasis Registry, Dermavant, Dermira, and Novartis. Dr Thaçi has received grant/research support from and served on a scientific advisory board and a speakers bureau for AbbVie, Almirall, Amgen, Biogen Idec, Boehringer Ingelheim, Eli Lilly, Galapagos, Galderma, Janssen-Cilag, Leo Pharma, Novartis, Pfizer, Regeneron, Roche, Sandoz-Hexal, Sanofi, Target-Solution, and UCB. Dr Sofen has served as a clinical investigator for AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, Janssen, Leo Pharma, Novartis, and Sun Pharma. Dr Kircik has received research grants from AbbVie, Allergan, Almirall, Amgen, Arcutis, Boehringer Ingelheim, Breckinridge Pharma, Bristol Myers Squibb, Celgene, Cellceutix, Centocor, Combinatrix, Connetics, Coria, Dermavant, Dermira, Dow Pharma, Dr Reddy's Laboratories, Eli Lilly, Galderma, Genentech, GlaxoSmithKline, Idera, Johnson & Johnson, Leo Pharma, Maruho, Merck, Medicis, Novartis AG, Pfizer, PharmaDerm, Promius, Stiefel, Sun Pharma, UCB, Valeant, and XenoPort; has received honoraria from AbbVie, Allergan, Almirall, Amgen, Arcutis, Biogen Idec, Bristol Myers Squibb, Celgene, Cipher, Connetics, Dermavant, Dermira, Dr Reddy's Laboratories, Eli Lilly, Galderma, Genentech, GlaxoSmithKline, Johnson & Johnson, Leo Pharma, Merck, Novartis AG, PharmaDerm, Promius, Serono (Merck Serono International SA), Stiefel, Sun Pharma, Taro, UCB, and Valeant. Dr Gordon has received grant support and consulting fees from AbbVie, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eli Lilly, Janssen, Novartis, and UCB, and has received consulting fees from Amgen, Almirall, Dermira, Leo Pharma, Pfizer, and Sun Pharma. Dr Foley has received grant support from Amgen, Bristol Myers Squibb, Celgene, Eli Lilly, Galderma, Janssen, Leo Pharma, Merck, Novartis, Pfizer, Sanofi, and Sun Pharma; has served as an investigator for AbbVie, Amgen, Arcutis, Argenx, Aslan, AstraZeneca, Boehringer Ingelheim, Botanix, Bristol Myers Squibb, Celgene, Celtaxsys, CSL, Cutanea, Dermira, Eli Lilly, Evelo, Galderma, Genentech, Geneseq, GlaxoSmithKline, Hexima, Janssen, Kymab, Leo Pharma, Merck, Novartis, Pfizer, Regeneron, Reistone, Roche, Sanofi, Sun Pharma, Teva, UCB, and Valeant; has served on advisory boards for AbbVie, Amgen, Aslan, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eli Lilly, Galderma, GlaxoSmithKline, Janssen, Leo Pharma, Mayne Pharma, MedImmune, Novartis, Pfizer, Sanofi, Sun Pharma, UCB, and Valeant; has served as a consultant for Aslan, Bristol Myers Squibb, Eli Lilly, Galderma, GenesisCare, Hexima, Janssen, Leo Pharma, Mayne Pharma, Novartis, Pfizer, Roche, and UCB; has received travel grants from AbbVie, Eli Lilly, Galderma, Janssen, Leo Pharma, Merck, Novartis, Pfizer, Roche, Sanofi, and Sun Pharma; and has served as a speaker for or received honoraria from AbbVie, Amgen, Celgene, Eli Lilly, Galderma, GlaxoSmithKline, Janssen, Leo Pharma, Merck, Novartis, Pfizer, Roche, Sanofi, Sun Pharma, and Valeant. Dr Rich has received research grants as a principal investigator on pharmaceutical trials from AbbVie, Arcutis, Bristol Myers Squibb, Dermavant, Eli Lilly, Janssen, Novartis, Sun Pharma, and UCB. Dr Paul has received grants from and has been a consultant for AbbVie, Almirall, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eli Lilly, Janssen, Leo Pharma, Merck, Mylan, Novartis, Pfizer, Sandoz, and UCB. Dr Bagel has received research funds payable to the Psoriasis Treatment Center of New Jersey from AbbVie, Amgen, Arcutis, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, CorEvitas' (Corrona) Psoriasis Registry, Dermavant, Dermira/UCB, Eli Lilly, Glenmark, Janssen Biotech, Kadmon, Leo Pharma, Lycera, Menlo Therapeutics, Novartis, Pfizer, Regeneron, Sun Pharma, Taro, and Valeant; has served as a consultant for AbbVie, Amgen, Celgene, Eli Lilly, Janssen Biotech, Novartis, Sun Pharma, and Valeant; and has served as a speaker for AbbVie, Celgene, Eli Lilly, Janssen Biotech, and Novartis. Dr Colston, Dr Sekaran, Ms Linaberry, and Dr Banerjee are employees of and shareholders in Bristol Myers Squibb. Dr Throup and Dr Kundu were employees of and shareholders in Bristol Myers Squibb at the time of study conduct. Dr Papp has served on a speakers bureau for AbbVie, Amgen, Astellas, Celgene, Eli Lilly, Galderma, Janssen, Kyowa Hakko Kirin, Leo Pharma, Merck Sharp & Dohme, Novartis, Pfizer, and Valeant; has received grant/research support from AbbVie, Akros, Allergan, Amgen, Anacor, Arcutis, AstraZeneca, Baxalta, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Coherus, Dermira, Dow Pharma, Eli Lilly, Galderma, Genentech, GlaxoSmithKline, Janssen, Kyowa Hakko Kirin, Leo Pharma, MedImmune, Meiji Seika Pharma, Merck Serono, Novartis, Pfizer, Regeneron, Roche, Sanofi Genzyme, Takeda, UCB, and Valeant; has served as a consultant for AbbVie, Akros, Amgen, Arcutis, Astellas, AstraZeneca, Baxalta, Baxter, Boehringer Ingelheim, Bristol Myers Squibb, CanFite, Celgene, Coherus, Dermira, Dow Pharma, Eli Lilly, Forward Pharma, Galderma, Genentech, Janssen, Kyowa Hakko Kirin, Leo Pharma, Meiji Seika Pharma, Merck Serono, Merck Sharp & Dohme, Mitsubishi Pharma, Novartis, Pfizer, Regeneron, Roche, Sanofi Genzyme, Takeda, UCB, and Valeant; has received honoraria from AbbVie, Akros, Amgen, Baxter, Boehringer Ingelheim, Celgene, Coherus, Eli Lilly, Forward Pharma, Galderma, GlaxoSmithKline, Janssen, Kyowa Hakko Kirin, Merck Serono, Merck Sharp & Dohme, Novartis, Pfizer, Takeda, UCB, and Valeant; and has served as scientific officer or on a steering committee/advisory board for AbbVie, Akros, Amgen, Anacor, Astellas, Baxter, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Dow Pharma, Eli Lilly, Galderma, Janssen, Kyowa Hakko Kirin, Merck Serono, Merck Sharp & Dohme, Novartis, Pfizer, Regeneron, Sanofi Genzyme, and Valeant., (Copyright © 2022 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Psoriasis is a chronic immune-mediated inflammatory disease. Beyond the physical dimensions, the disease has an extensive emotional and psychosocial effect on patients, influencing their quality of life, social life and interpersonal relationships. Thus patient-reported outcomes are a crucial instrument for the evaluation of disease burden. Navigating life in times of the COVID-19 pandemic is challenging, especially for persons suffering from chronic diseases. We here analyzed the impact of lockdown restrictions on psoriasis patients., Objective: To compare the Dermatology Life Quality Index (DLQI) before and during the COVID-19 pandemic of patients with psoriasis., Methods: Retrospective longitudinal analysis in adult patients with moderate to severe psoriasis undergoing biologic treatment between January 2020 and January 2021. DLQI, patient demographics, Psoriasis Area and Severity Index (PASI), and recent biologic treatment were recorded., Results: 103 patients were identified, of whom 19 had additional psoriatic arthritis. Female (n = 29) and male (n = 74) patients were distributed 1 to 3. Median age of patients was 54 years (range 18-85). All patients received biologic systemic treatment: anti-IL-23 (n = 39), anti-IL-17A (n = 30), anti-IL-12/23 (n = 25), or anti-TNFα (n = 9). Comparing DLQI scores before the COVID-19 pandemic and under lockdown restriction showed improved DLQI scores over time. Further analysis displayed that patients mostly ticked "not relevant" on social activities during lockdown. Thus, the DLQI scores may be artificial improved and may not really reflect the actual disease burden., Conclusions: Psoriasis patients showed a contrary improvement of life quality despite harsh COVID-19 lockdown suggesting that DLQI should be modified when social life is restricted., Competing Interests: All authors have read the journal’s policy and the authors of this manuscript have the following competing interests. Diamant Thaçi has received honoraria and lecture fees from AbbVie, Almirall, Amgen, Biogen Idec, Boehringer Ingelheim, Bristol Myers Squibb, Janssen, Leo Pharma, Novartis, Pfizer, Roche-Posay, Sanofi, Target-Solution, and UCB. All other authors have none to declare. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Importance: Psoriasis is a chronic disease requiring long-term management; understanding the long-term safety profiles of psoriasis treatments, such as bimekizumab, is important., Objective: To evaluate the 2-year safety profile of bimekizumab in patients with moderate to severe plaque psoriasis., Design, Setting, and Participants: Safety data were pooled from a cohort of patients from 4 phase 2 randomized clinical trials (BE ABLE 1, BE ABLE 2, PS0016, and PS0018) and 4 phase 3 randomized clinical trials (BE VIVID, BE READY, BE SURE, and BE BRIGHT) to include 2 years of study treatment. Data were obtained on adults with moderate to severe plaque psoriasis (Psoriasis Area and Severity Index level ≥12, ≥10% body surface area affected by psoriasis, and an Investigator's Global Assessment score ≥3 on a 5-point scale) who were eligible for systemic psoriasis therapy and/or phototherapy., Interventions: Included patients received 1 or more doses of bimekizumab during the phase 2 or phase 3 trials., Main Outcomes and Measures: Treatment-emergent adverse events (TEAEs), serious TEAEs, and TEAEs leading to treatment discontinuation are reported using exposure-adjusted incidence rates (EAIRs) per 100 person-years., Results: A total of 1789 patients (1252 [70.0%] men; mean [SD] age, 45.2 [13.5] years) were treated with 1 or more doses of bimekizumab across the phase 2/3 trials and were included in these analyses; total bimekizumab exposure was 3109.7 person-years. TEAEs occurred at an EAIR of 202.4 per 100 person-years and did not increase with longer duration of bimekizumab exposure. The 3 most frequently reported TEAEs were nasopharyngitis (19.1 per 100 person-years; 95% CI, 17.4-20.9 per 100 person-years), oral candidiasis (12.6 per 100 person-years; 95% CI, 11.3-14.0 per 100 person-years), and upper respiratory tract infection (8.9 per 100 person-years; 95% CI, 7.8-10.1 per 100 person-years). Most oral candidiasis events were mild or moderate; 3 events led to discontinuation. The EAIRs of inflammatory bowel disease (0.1 per 100 person-years; 95% CI, 0.0-0.3 per 100 person-years), adjudicated suicidal ideation and behavior (0.0 per 100 person-years; 95% CI, 0.0-0.2 per 100 person-years), and adjudicated major adverse cardiac events (0.5 per 100 person-years; 95% CI, 0.3-0.8 per 100 person-years) were low., Conclusions and Relevance: In these pooled analyses of data from a cohort of patients from 8 randomized clinical trials, bimekizumab was well tolerated aside from an increased incidence of mild to moderate oral candidiasis. No safety signals were observed compared with previous reports, and there was no increased risk of AEs with longer duration of bimekizumab exposure.

Generalized pustular psoriasis (GPP) is a rare, severe, potentially life-threatening, autoinflammatory, neutrophilic skin disease that may be accompanied by fever and leukocytosis. This paper describes the current state of knowledge on GPP in terms of classification, (differential) diagnosis and prevalence. We present a comparison of the genetics and pathoimmunology of GPP and psoriasis vulgaris with the central mechanisms of autoimmunology and autoinflammation. The currently available therapeutic options, expert recommendations for therapy, and data from early clinical trials investigating targeted therapies will be summarized. We present the results of our discussion with 13 experts for psoriasis vulgaris and GPP and give an integrated overview of indication and therapy based on our personal experience and present an outlook on further research questions. Collectively, this article highlights the high unmet need in GPP, as there exists no satisfactory method of diagnosis or treatment to date and new treatment options will be of great therapeutic benefit to those affected., (© 2022 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd.)

Purpose: Guselkumab, an interleukin (IL)-23 inhibitor, effectively treats moderate-to-severe plaque psoriasis., Materials and Methods: ECLIPSE, was a Phase 3, multicenter, 56-week, double-blinded, active-comparator study of guselkumab vs. secukinumab (IL-17A inhibitor) in patients with moderate-to-severe psoriasis. Patients were treated with guselkumab 100 mg ( n  = 534) or secukinumab 300 mg ( n  = 514) through week 44. Efficacy (at least a 90% and 100% improvement from baseline in Psoriasis Area and Severity Index [PASI 90 and PASI 100], Investigator's Global Assessment [IGA] 0/1, and IGA 0) was analyzed across subpopulations defined by baseline: age (<45, 45 to <65, and ≥65 years old), body weight, body mass index (BMI), psoriasis disease severity (body surface area, disease duration, PASI, and IGA), psoriasis by body regions (head, trunk, upper and lower extremities), and prior psoriasis medication history at week 48., Results: Overall, 1048 patients were randomized. At week 48, numerically greater proportions of patients achieved PASI 90, PASI 100, IGA 0/1, and IGA 0 with guselkumab vs. secukinumab regardless of baseline age, body weight, BMI, disease severity, body region, and prior medication. The largest differences were in patients ≥65 years old and patients weighing >100 kg., Conclusions: Guselkumab treatment provided greater efficacy vs. secukinumab at week 48 in most subpopulations of patients with psoriasis.

Objective: To investigate the drug survival of secukinumab (SEC), ustekinumab (UST), and certolizumab pegol (CZP) in real-world conditions and to identify the predictors and reasons for treatment discontinuation., Methods: We performed a 2-year retrospective single-center analysis of 110 treatment courses in 98 patients with moderate to severe plaque-type psoriasis and/or psoriatic arthritis (SEC n  = 68; UST n  = 29; and CZP n  = 13). Drug survival was examined using the Kaplan-Meier analysis and the influence of demographic factors on drug survival with Cox regression analysis., Results: Drug survival rates at 12 and 18 months were respectively 68.5% and 59% for the entire study population, 85% and 69% for UST, 68% and 59% for SEC, and 34% for CZP. Both UST and SEC showed a significantly longer survival rate compared to CZP ( p <.05), but not between each other. A total of 30 treatment discontinuations were observed, predominantly due to loss of efficacy and adverse events. Treatment selection predicted the survival rate. Other predictors could not be identified., Conclusions: Drug survival is the resultant of many factors such as long-term effectiveness, safety, compliance, and convenience of use. UST and SEC had higher retention rates in comparison with CZP.

Brodalumab is approved for treatment of moderate-to-severe plaque psoriasis. Here, we assess the safety profile of brodalumab using pooled safety data from 5 phase II/III trials of brodalumab 140 mg or 210 mg. In total, 4,464 patients received brodalumab, representing 8,891.6 patient-years of exposure. During the placebo-controlled 12-week induction period, rates of serious adverse events per 100 patient-years were 10.8 and 9.6 (brodalumab 140 mg and 210 mg, respectively) vs 4.3 and 6.5 (ustekinumab and placebo, respectively); infections were the most frequent serious adverse event. Rates of serious adverse events during the comparator-controlled 52-week period were 14.4, 10.2 and 8.3 per 100 patient-years for brodalumab 210 mg, brodalumab 140 mg, and ustekinumab, respectively. Brodalumab was not associated with increased risks of malignancy, major adverse cardiac events, suicidal ideation and behaviour, or fatal events. Overall, brodalumab demonstrated an acceptable safety profile in short- and long-term treatment.

Background: It is challenging to select the most appropriate biologic treatment for patients with moderate-to-severe plaque psoriasis., Objective: To compare speed of onset and level of skin improvement between the interleukin (IL)-17A antagonist ixekizumab and the IL-23 p19 inhibitors guselkumab, tildrakizumab, and risankizumab in patients with moderate-to-severe plaque psoriasis., Methods: Using data from controlled clinical trials, both adjusted indirect comparisons (AICs) and matching adjusted indirect comparisons (MAICs) were performed to determine the risk difference (RD) between ixekizumab and each IL-23 p19 inhibitor for the proportion of patients with ≥75%/90%/100% improvement compared with baseline in Psoriasis Area and Severity Index (PASI 75/90/100) up to week 12. Placebo, etanercept, or ustekinumab were used as the comparator bridge., Results: In all (M)AICs, RDs generally significantly favored ixekizumab over guselkumab (placebo bridge), tildrakizumab (placebo or etanercept bridge), and risankizumab (placebo or ustekinumab bridge) from the earliest assessment time (≥ week 2) to week 12 when considering PASI 75/90/100 responses., Conclusion: Ixekizumab provides a faster onset of effect and earlier clinical benefits than guselkumab, tildrakizumab, or risankizumab in patients with moderate-to-severe psoriasis, as reflected by higher levels of skin improvement than with these IL-23 p19 inhibitors up to week 12.

Topical therapies have been available for the treatment of psoriasis for several decades. Despite this and the availability of several types of topicals, with varying potency, and numerous vehicles of administration, the majority of clinical data and guidance is on short-term use in the management of psoriasis. The aim of this manuscript is to review the unmet needs that exist in the long-term management of psoriasis and provide the dermatology community with an understanding that a treatment regimen with topical therapies could be the best treatment option at least for some phases of this chronic relapsing disease. We present a 'call to action' on the need for clinical alignment on terminology in the field and recommend the term 'long-term management' be adopted as the most appropriate in the context of this manuscript. This expert opinion report provides a detailed review of the limited evidence available regarding long-term use of topical therapies for the management of psoriasis, alongside our key considerations and recommendations to assist dermatologists with the implementation of topicals as part of long-term management strategies. Long-term management should be considered mandatory to ensure patients receive appropriate proactive treatment which may help optimize adherence and long-term outcomes.

Generalized pustular psoriasis (GPP) is a rare, severe neutrophilic skin disorder characterized by sudden widespread eruption of superficial sterile pustules with or without systemic inflammation. GPP flares can be life-threatening if untreated due to potential severe complications such as cardiovascular failure and serious infections. Currently, there are no GPP-specific therapies approved in the USA or Europe. Retinoids, cyclosporine, and methotrexate are the most commonly used non-biologic therapies for GPP. The evidence that supports the currently available treatment options is mainly based on case reports and small, open-label, single-arm studies. However, recent advances in our understanding of the pathogenic mechanisms of GPP and the identification of gene mutations linked to the disease have paved the way for the development of specific targeted therapies that selectively suppress the autoinflammatory and autoimmune mechanisms induced during GPP flares. Several biologic agents that target key cytokines involved in the activation of inflammatory pathways, such as tumor necrosis factor-α blockers and interleukin (IL)-17, IL-23, and IL-12 inhibitors, have emerged as potential treatments for GPP, with several being approved in Japan. The evidence supporting the efficacy of these agents is mainly derived from small, uncontrolled trials. A notable recent advance is the discovery of IL36RN mutations and the central role of IL-36 receptor ligands in the pathogenesis of GPP, which has defined key therapeutic targets for the disease. Biologic agents that target the IL-36 pathway have demonstrated promising efficacy in patients with GPP, marking the beginning of a new era of targeted therapy for GPP., (© 2022. The Author(s).)

Objective: Making a differential diagnosis of psoriatic arthritis (PsA) is not straightforward. This is partly because of its heterogeneous presentation and partly because many patients with PsA are initially diagnosed with psoriasis and treated in primary care or by dermatologists, with referral to rheumatologists being delayed. Once diagnosed, optimal disease control requires frequent specialist monitoring, adjustment or switching of therapies, and management of comorbidities and concomitant diseases, as well as attention to patients' overall well-being. Given the breadth of expertise that diagnosis and management of PsA requires, we sought to define a collaborative, structured framework that supports the optimisation of multidisciplinary care for patients with PsA in Europe., Methods: An expert panel comprising four rheumatologists, three dermatologists, two specialist nurses and one psychologist-from Spain, the United Kingdom, The Netherlands, Germany, France and Italy-met face-to-face to take part in a modified Delphi exercise., Results: The result of this exercise is a set of recommendations that are based on combining published evidence with the panel's extensive clinical experience. Recommendations can be implemented in a number of ways, but the central call-to-action of this framework is the need for improved collaboration between dermatologists (or primary care physicians) and rheumatologists. This could occur in a variety of different formats: standard referral pathways, multidisciplinary physician meetings to discuss patient cases, or 'one stop', combined clinics., Conclusion: We anticipate that when the majority of patients with PsA receive regular multidisciplinary care, improved patient outcomes will follow, although robust research is needed to explore this assumption., (Copyright © 2021 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Background: Topical psoriasis treatment relies on a reactive rather than a long-term proactive approach to disease relapse., Objective: Assess long-term efficacy and safety of proactive psoriasis management with twice-weekly calcipotriene 0.005%/betamethasone dipropionate 0.064% (Cal/BD) foam., Methods: Phase III trial (NCT02899962) included a 4-week open-label lead-in phase (Cal/BD foam once daily) and a 52-week, randomized, double-blind, maintenance phase. A total of 545 patients achieved treatment success (physician's global assessment "clear"/"almost clear," ≥2-grade improvement from baseline) and were randomized to proactive management (Cal/BD foam; n = 272) or reactive management (vehicle foam; n = 273) twice-weekly, with rescue treatment of Cal/BD foam once daily for 4 weeks upon relapse. Primary endpoint was time to first relapse (physician's global assessment "mild" or higher)., Results: A total of 251 randomized patients (46.1%) completed the trial. Median time to first relapse was 56 days (proactive) and 30 days (reactive). Patients in the proactive group had an additional 41 days in remission compared with the reactive group over 1 year (P < .001). Number of relapses per year of exposure was 3.1 (proactive) and 4.8 (reactive). Cal/BD foam was well tolerated., Limitations: Maintenance phase dropout rate (53.9%) was within the expected range but provides challenges in statistical analysis., Conclusion: Long-term proactive management with Cal/BD foam demonstrated superior efficacy vs reactive management., (Copyright © 2020 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Psoriasis is a chronic disease requiring long-term treatment strategies. Optimal strategies should include initial rapid relief of symptoms followed by long-term management to maintain remission. This 4-week open-label phase of a long-term proactive management phase 3 trial aimed to select responders to once daily, fixed-dose combination calcipotriene 0.005% and betamethasone dipropionate 0.064% (Cal/BD) foam in adults with psoriasis and assess patient-reported outcomes., Method: This phase 3 trial in adults with psoriasis included a 4-week open-label lead-in phase to determine treatment success prior to entering the randomized maintenance phase. Success was defined as Physician Global Assessment (PGA) score &lsquo;clear&rsquo;/&lsquo;almost clear&rsquo; (PGA &lt;2) with &ge;2-grade improvement from baseline. Those achieving treatment success at week 4 entered the maintenance phase; non-responders were withdrawn from the trial., Results: 650 patients enrolled in the open-label phase, and 623 were treated with Cal/BD foam for 4 weeks; 521 (80%) patients achieved treatment success and were included in the maintenance phase. In those patients achieving success (responders), 21.1% and 78.9% achieved a PGA score of &lsquo;clear&rsquo; and &lsquo;almost clear&rsquo;, respectively. Mean change from baseline in modified Psoriasis Area and Severity Index (&plusmn; standard deviation [SD]) and body surface area (&plusmn; SD) in responders at week 4 was &minus;82.1% (16.4%) and &minus;56.6% (38.3%), respectively. Mean Dermatology Life Quality Index score reduced by 6.0 from baseline to week 4 (n=521). 17.7% of patients experienced AEs; with only one severe AE reported., Conclusion: Cal/BD foam was highly efficacious and well tolerated during the 4-week lead-in phase of PSO-LONG. J Drugs Dermatol. 2021;20(4):436-441, doi:10.36849/JDD.5728.

Genital psoriasis affects 2-5% of psoriasis patients; generalised plaque or intertriginous psoriasis also affects the genital area in 29-40% of cases. Anogenital psoriasis has been associated with significant quality of life impairments, but little is known about specific patient needs/treatment goals. This study aimed to examine the overall and sex-related disease burden, patient needs and treatment benefits in patients with anogenital psoriasis, compared to patients with psoriasis not affecting the anal/genital areas. Within the cross-sectional nationwide survey, 2,009 participants were consecutively recruited in 157 randomly assigned German dermatology practices and clinics, according to the following inclusion criteria aged 18 years or over; diagnosis of psoriasis vulgaris; ability to answer the questionnaires; and written informed consent. Based on a high-resolution grid on the topical distribution of psoriasis, two groups were formed: anogenital psoriasis (n = 622) and comparison group (n = 1,303). Clinical severity was assessed by the Psoriasis Area and Severity Index (PASI). Patients completed the EuroQoL visual analogue scale (EQ VAS), the Dermatology Life Quality Index (DLQI), and the Patient Benefit Index (PBI). Patients with anogenital psoriasis had higher PASI (13.0±10.6 vs. 8.9±7.6, P < 0.001) and more DLQI impairments (8.9±6.9 vs. 7.0±6.2, P = 0.002) than controls. At the item-level, they also reported more sex-related DLQI impairments (DLQI-i9: 0.5±0.8 vs. 0.3±0.7, P < 0.001) and treatment needs (PBI-i17: 2.2±1.8 vs. 1.9±1.8, P = 0.001). A great percentage of missing/not-relevant responses was found for sex-related items (23.3-41.9%). These results suggest that the assessment of sex-related impairments and treatment needs should be prioritised in patients with anogenital psoriasis. Questionnaires may be used as a less uncomfortable way for patients to discuss their genital lesions and sexual function during healthcare visits. However, the great percentage of missing/not-relevant responses to sex-related items calls for in-depth assessments and effective patient-physician communication regarding these sensitive topics., Competing Interests: The funder (Wyeth/Pfizer Germany) provided research support, but no honoraria, for authors MA, UM, KR, DT and WHB, but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of these authors are articulated in the ‘author contributions’ section. In addition, MA, KR, DT, WHB and NK has served as consultant, and/or paid speaker and/or has received research grants, honoraria and/or got travel expenses reimbursed for consulting and/or scientific lectures, and/or participated in clinical trials sponsored by companies that manufacture drugs used for the treatment of Psoriasis, including AbbVie (MA, KR, DT, WHB, NK), Affibody (KR), Almirall (MA, KR, DT, WHB), Amgen (MA, KR), Avillion (KR), Biogen-Idec (MA, KR, DT), Boehringer Ingelheim (MA, KR, DT), Bristol-Myers Squibb (KR), Celgene (MA, DT, WHB, NK), Centocor (MA, KR), Covagen (KR), Dignity (DT), Eli Lilly (MA, KR, DT, WHB, NK), Forward Pharma (KR), Fresenius Medical Care (KR), Galapagos (KR), Galderma (MA, DT), GlaxoSmithKline (KR, DT), Janssen-Cilag (MA, KR, DT, NK), Kyowa Kirin (KR), Leo Pharma (MA, KR, DT, WHB), Maruho (DT), Medac (MA, KR, DT), Medimmune (DT), Merck Sharp & Dohme (MA, KR, DT), Miltenyi Biotec (KR), Morphosis (DT), Mundipharma (MA), Novartis (MA, KR, DT, WHB, NK), Ocean Pharma (KR), Pfizer (MA, KR, DT, NK), Regeneron (KR, DT), Samsung Bioepis (KR, DT), Sandoz (MA, DT), Sanofi-Aventis (KR, DT), Sun Pharma (KR, DT), Takeda (KR, DT), UCB (KR, DT, WHB), Valeant (KR), Xenoport (MA, KR). NdS, AL, AD, and RS declare no conflict of interests. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Psoriasis may cause considerable disease burden. The involvement of sexually-sensitive/visible body areas has been associated with decreased quality of life (QoL), more depressive symptoms and stigmatisation experiences. To characterise the topical distribution of psoriasis in sexually-sensitive and visible areas, to examine its impact on QoL and to determine which specific patient needs should be addressed in routine care. Patients with psoriasis vulgaris were recruited within a cross-sectional nationwide survey, involving 157 randomly assigned German dermatology practices/clinics. The main outcome measures were the EuroQoL visual analogue scale (EQ VAS), the Dermatology Life Quality Index (DLQI), the Patient Needs Questionnaire (PNQ) and a grid scheme for topical distribution of psoriasis. The sample included 2,009 patients (43.7% female; 21.8% ≥ 65 years; 64.2% with lesions in sexually-sensitive areas and 86.2% with lesions in visible areas). Patients with concomitant involvement of sexually-sensitive and visible areas presented increased DLQI impairments relative to patients with no involvement of sexually-sensitive or visible areas (F (3, 1723)  = 4.091, p = 0.007). Significant differences were also found for patient needs dimensions (PNQ) depending on the body areas affected (F (15, 4602)  = 2.936, p < 0.001). Significant effects of gender and age group were also observed. Increased disease severity, lesions in both sexually-sensitive/visible or only visible areas, and increased QoL impairment were associated with specific patient needs. These results highlight the need for proactive evaluation of difficult-to-communicate impairments and the requirements for patient-centred routine care.

Background: Psoriasis is an autoimmune disease that affects approximately 100 million people worldwide, and is a disease that can be ameliorated by anti-cytokine treatment. We aimed to compare the efficacy and safety of risankizumab with adalimumab in patients with moderate-to-severe plaque psoriasis., Methods: IMMvent was a phase 3, randomised, double-blind, active-comparator-controlled trial completed at 66 clinics in 11 countries. Eligible patients were aged 18 years or older with moderate-to-severe chronic plaque psoriasis. Patients were randomly assigned 1:1 using interactive response technology to receive 150 mg risankizumab subcutaneously at weeks 0 and 4 or 80 mg adalimumab subcutaneously at randomisation, then 40 mg at weeks 1, 3, 5, and every other week thereafter during a 16-week double-blind treatment period (part A). For weeks 16-44 (part B), adalimumab intermediate responders were re-randomised 1:1 to continue 40 mg adalimumab or switch to 150 mg risankizumab. In part A, participants and investigators were masked to study treatment. Randomisation was stratified by weight and previous tumour necrosis factor inhibitor exposure. Co-primary endpoints in part A were a 90% improvement from baseline (PASI 90) and a static Physician's Global Assessment (sPGA) score of 0 or 1 at week 16, and for part B was PASI 90 at week 44 (non-responder imputation). Efficacy analyses were done in the intention-to-treat population and safety analyses were done in the safety population (all patients who received at least one dose of study drug or placebo). This study is registered with ClinicalTrials.gov, number NCT02694523., Findings: Between March 31, 2016, and Aug 24, 2017, 605 patients were randomly assigned to receive either risankizumab (n=301, 50%) or adalimumab (n=304, 50%). 294 (98%) of patients in the risankizumab group and 291 (96%) in the adalimumab group completed part A, and 51 (96%) of 53 patients re-randomised to risankizumab and 51 (91%) of 56 patients re-randomised to continue adalimumab completed part B. At week 16, PASI 90 was achieved in 218 (72%) of 301 patients given risankizumab and 144 (47%) of 304 patients given adalimumab (adjusted absolute difference 24·9% [95% CI 17·5-32·4]; p<0·0001), and sPGA scores of 0 or 1 were achieved in 252 (84%) patients given risankizumab and 252 (60%) patients given adalimumab (adjusted absolute difference 23·3% [16·6-30·1]; p<0·0001). In part B, among adalimumab intermediate responders, PASI 90 was achieved by 35 (66%) of 53 patients switched to risankizumab and 12 (21%) of 56 patients continuing adalimumab (adjusted absolute difference 45·0% [28·9-61·1]; p<0·0001) at week 44. Adverse events were reported in 168 (56%) of 301 patients given risankizumab and 179 (57%) of 304 patients given adalimumab in part A, and among adalimumab intermediate responders, adverse events were reported in 40 (75%) of 53 patients who switched to risankizumab and 37 (66%) of 56 patients who continued adalimumab in part B., Interpretation: Risankizumab showed significantly greater efficacy than adalimumab in providing skin clearance in patients with moderate-to-severe plaque psoriasis. No additional safety concerns were identified for patients who switched from adalimumab to risankizumab. Treatment with risankizumab provides flexibility in the long-term treatment of psoriasis., Funding: AbbVie and Boehringer Ingelheim., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Objective: In 2016, members of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA), in collaboration with KPMG LLP (UK), conducted a study to measure care in psoriatic arthritis (PsA). A key finding was that centers do not usually have processes in place to measure the effect of improved quality of care. Our objectives were to identify and select best-practice indicators to enable PsA caregivers to assess and monitor the outcomes of specific initiatives aimed at improving care in 4 focus areas: (1) shortening time to diagnosis; (2) improving multidisciplinary collaboration; (3) optimizing disease management; and (4) improving disease monitoring., Methods: (1) Structured review of scientific and grey literature to obtain evidence for a long list of 100 potential indicators across the 4 focus areas; (2) survey expert rheumatologists and dermatologists to review the long list and identify the most meaningful and feasible indicators for use in day-to-day practice; (3) consensus discussion to identify a shortlist of indicators based on predefined selection criteria; (4) electronic group discussion to refine definitions of shortlisted indicators and targets; and (5) review of the shortlisted indicators at the annual GRAPPA meeting in July 2018 to ensure the indicators meet the preliminary criteria., Results: The expert group arrived at a consensus with a shortlist of 8 best-practice indicators across 4 key focus areas aligned with the patient pathway., Conclusion: There were 8 evidence-based best-practice indicators and respective targets that were identified to enable the monitoring of quality of care and target improvements.

Psoriasis increases the risk of cardiovascular (CV) disease. Secukinumab, a fully human monoclonal antibody against IL-17A, shows significant efficacy in psoriasis, but effects on CV markers are unknown. CARIMA (Evaluation of Cardiovascular Risk Markers in Psoriasis Patients Treated with Secukinumab) was a 52-week, randomized, double-blind, placebo-controlled, exploratory trial in patients with moderate to severe plaque psoriasis without clinical CV disease. Patients were randomly assigned to receive 300 mg or 150 mg secukinumab until week 52 or to receive placebo until week 12 and then 300 mg or 150 mg secukinumab until week 52. The primary outcome was endothelial function measured by flow-mediated dilation (FMD). Baseline FMD was significantly lower in psoriasis patients than healthy volunteers (4.4 ± 3.9% vs. 6.1 ± 3.3%, P = 0.01). At week 12, baseline-adjusted mean FMD was numerically higher in patients receiving secukinumab versus those receiving placebo, but this difference (300-mg group, +1.2%; 150-mg group, +0.76%; P = 0.223 and P = 0.403 by analysis of covariance) did not reach significance. At week 52, FMD increased across groups. FMD was significantly higher than baseline in patients receiving the label dose of 300 mg secukinumab for 52 weeks (+2.1%, 95% confidence interval = 0.8-3.3; P = 0.0022). Other relevant CV markers were unchanged. CARIMA indicates that secukinumab might have a beneficial effect on CV risk by improving the endothelial function of patients with plaque psoriasis., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Tyrosine kinase 2 (TYK2) signaling pathways, which mediate cytokine signaling, are implicated in the pathophysiology of psoriasis. Selective inhibitors of TYK2 may be effective in treating psoriasis., Methods: We conducted a phase 2, double-blind trial of a TYK2 inhibitor, BMS-986165, in adults with moderate-to-severe psoriasis, excluding patients with a previous lack of response to agents targeting cytokine signaling through the same tyrosine kinase pathway. Patients were randomly assigned to receive the drug orally at a dose of 3 mg every other day, 3 mg daily, 3 mg twice daily, 6 mg twice daily, or 12 mg daily or to receive placebo. The primary end point was a 75% or greater reduction from baseline in the Psoriasis Area and Severity Index (PASI) score at week 12 (higher scores indicate greater severity of psoriasis)., Results: A total of 267 patients received at least one dose in an intervention group of the trial. At week 12, the percentage of patients with a 75% or greater reduction in the PASI score was 7% (3 of 45 patients) with placebo, 9% (4 of 44 patients) with 3 mg of BMS-986165 every other day (P=0.49 vs. placebo), 39% (17 of 44 patients) with 3 mg daily (P<0.001 vs. placebo), 69% (31 of 45 patients) with 3 mg twice daily (P<0.001 vs. placebo), 67% (30 of 45 patients) with 6 mg twice daily (P<0.001 vs. placebo), and 75% (33 of 44 patients) with 12 mg daily (P<0.001 vs. placebo). There were three serious adverse events in patients receiving the active drug, as well as one case of malignant melanoma 96 days after the start of treatment., Conclusions: Selective inhibition of TYK2 with the oral agent BMS-986165 at doses of 3 mg daily and higher resulted in greater clearing of psoriasis than did placebo over a period of 12 weeks. Larger and longer-duration trials of this drug are required to determine its safety and durability of effect in patients with psoriasis. (Funded by Bristol-Myers Squibb; ClinicalTrials.gov number, NCT02931838 .).

Background: Certolizumab pegol, the only Fc-free, PEGylated anti-tumor necrosis factor biologic, demonstrated clinically meaningful improvements suggestive of a positive risk-benefit balance in phase 2 studies in adults with moderate-to-severe chronic plaque psoriasis., Objective: Assess certolizumab efficacy and safety versus placebo in phase 3 studies., Methods: Patients with moderate-to-severe chronic plaque psoriasis were randomized 2:2:1 to certolizumab 400 mg, certolizumab 200 mg, or placebo every 2 weeks. At week 16, certolizumab-treated patients achieving a 50% reduction in Psoriasis Area and Severity Index continued treatment through week 48. Coprimary endpoints were week 16 responder rates, defined as a 75% reduction in Psoriasis Area and Severity Index and Physician's Global Assessment 0/1 (clear/almost clear) and ≥2-point improvement. Safety was assessed by treatment-emergent adverse events., Results: Week-16 endpoints were significantly greater for both doses of certolizumab versus placebo, and the responses were maintained through week 48. For most measures, improvement was numerically greater for certolizumab 400 mg. No unexpected safety signals were identified., Limitation: There was no active comparator., Conclusion: Treatment with either certolizumab 400 mg or 200 mg every 2 weeks was associated with significant and clinically meaningful improvements in moderate-to-severe psoriasis. The 400-mg dose could provide additional clinical benefit. The safety profile was consistent with the therapeutic class., (Copyright © 2018 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Secukinumab has demonstrated greater sustained skin clearance than ustekinumab through week 52, greater improvement in symptoms and health-related quality of life, and comparable safety profile., Objective: To assess the impact of secukinumab versus that of ustekinumab on complete relief from psoriasis-related symptoms, time to response in terms of health-related quality of life, and cumulative benefit among patients with moderate-to-severe plaque psoriasis., Methods: Psoriasis-related pain, itching, and scaling and the Dermatology Life Quality Index (DLQI) score were compared between treatments on the basis of time to complete relief of symptoms and time to DLQI response in the CLEAR trial. Cumulative benefit over 52 weeks based on Psoriasis Area and Severity Index score, symptom relief, and DLQI response were evaluated by area under the curve analysis., Results: Significantly more patients treated with secukinumab achieved complete relief of pain at weeks 16 and 52 (all P < .05). Complete relief of itching and scaling occurred significantly faster with secukinumab (median, 4 weeks faster for itching and 8 weeks faster for scaling [P < .001]). Response as measured by the DLQI was 4 weeks faster with secukinumab (P < .0001). Cumulative benefits were greater with secukinumab (all P < .05)., Limitations: Analyses were post hoc., Conclusion: This patient-reported outcome analysis confirms greater and sustained benefits of secukinumab versus those of ustekinumab treatment on patients' lives., (Copyright © 2017 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Randomized, controlled trials demonstrated efficacy and safety of apremilast for moderate-to-severe plaque psoriasis and psoriatic arthritis., Objective: Assess long-term safety of oral apremilast in psoriasis patients., Methods: Safety findings are reported for 0 to ≥156 weeks from the Efficacy and Safety Trial Evaluating the Effects of Apremilast in Psoriasis (ESTEEM) 1 and 2., Results: The 0 to ≥156-week apremilast-exposure period included 1184 patients treated twice daily with apremilast 30 mg (1902.2 patient-years). During 0 to ≤52 weeks, the adverse events (AEs) that occurred in ≥5% of patients included diarrhea, nausea, upper respiratory tract infection, nasopharyngitis, tension headache, and headache. From 0 to ≥156 weeks, no new AEs (affecting ≥5% of the population) were reported. AEs, serious AEs, and study drug discontinuations caused by AEs did not increase with long-term exposure. During the 0 to ≥156-week period, the rates of major cardiac events (exposure-adjusted incidence rate [EAIR] 0.5/100 patient-years), malignancies (EAIR 1.2/100 patient-years), depression (EAIR 1.8/100 patient-years), or suicide attempts (EAIR 0.1/100 patient-years) did not increase in comparison with the rates found during the 0 to ≤52-week period. No serious opportunistic infections, reactivation of tuberculosis, or clinically meaningful effects on laboratory measurements were reported., Limitations: This study had a high dropout rate (21% of patients ongoing >156 weeks); most were unrelated to safety concerns., Conclusions: Apremilast demonstrated an acceptable safety profile and was generally well tolerated for ≥156 weeks., (Copyright © 2017 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Tildrakizumab is a high-affinity, humanised, IgG1 κ antibody targeting interleukin 23 p19 that represents an evolving treatment strategy in chronic plaque psoriasis. Previous research suggested clinical improvement with inhibition of interleukin 23 p19. We did two phase 3 trials to investigate whether tildrakizumab is superior to placebo and etanercept in the treatment of chronic plaque psoriasis., Methods: We did two three-part, parallel group, double-blind, randomised controlled studies, reSURFACE 1 (at 118 sites in Australia, Canada, Japan, the UK, and the USA) and reSURFACE 2 (at 132 sites in Europe, Israel, and the USA). Participants aged 18 years or older with moderate-to-severe chronic plaque psoriasis (body surface area involvement ≥10%, Physician's Global Assessment [PGA] score ≥3, and Psoriasis Area and Severity Index [PASI] score ≥12) were randomised (via interactive voice and web response system) to tildrakizumab 200 mg, tildrakizumab 100 mg, or placebo in reSURFACE 1 (2:2:1), or to tildrakizumab 200 mg, tildrakizumab 100 mg, placebo, or etanercept 50 mg (2:2:1:2). Randomisation was done by region and stratified for bodyweight (≤90 kg or >90 kg) and previous exposure to biologics therapy for psoriasis. Investigators, participants, and study personnel were blinded to group allocation and remained blinded until completion of the studies. Assigned medication was identical in appearance and packaging. Tildrakizumab was administered subcutaneously at weeks 0 and 4 during part 1 and at week 16 during part 2 (weeks 12 and 16 for participants re-randomised from placebo to tildrakizumab; etanercept was given twice weekly in part 1 of reSURFACE 2 and once weekly during part 2). The co-primary endpoints were the proportion of patients achieving PASI 75 and PGA response (score of 0 or 1 with ≥2 grade score reduction from baseline) at week 12. Safety was assessed in the all-participants-as-treated population, and efficacy in the full-analysis set. These trials are registered with ClinicalTrials.gov, numbers NCT01722331 (reSURFACE 1) and NCT01729754 (reSURFACE 2). These studies are completed, but extension studies are ongoing., Findings: reSURFACE 1 ran from Dec 10, 2012, to Oct 28, 2015. reSURFACE 2 ran from Feb 12, 2013, to Sept 28, 2015. In reSURFACE 1, 772 patients were randomly assigned, 308 to tildrakizumab 200 mg, 309 to tildrakizumab 100 mg, and 155 to placebo. At week 12, 192 patients (62%) in the 200 mg group and 197 patients (64%) in the 100 mg group achieved PASI 75, compared with 9 patients (6%) in the placebo group (p<0·0001 for comparisons of both tildrakizumab groups vs placebo). 182 patients (59%) in the 200 mg group and 179 patients (58%) in the 100 mg group achieved PGA responses, compared with 11 patients (7%) in the placebo group (p<0·0001 for comparisons of both tildrakizumab groups vs placebo). In reSURFACE 2, 1090 patients were randomly assigned, 314 to tildrakizumab 200 mg, 307 to tildrakizumab 100 mg, 156 to placebo, and 313 to etanercept. At week 12, 206 patients (66%) in the 200 mg group, and 188 patients (61%) in the 100 mg group achieved PASI 75, compared with 9 patients (6%) in the placebo group and 151 patients (48%) in the etanercept group (p<0·0001 for comparisons of both tildrakizumab groups vs placebo; p<0·0001 for 200 mg vs etanercept and p=0·0010 for 100 mg vs etanercept). 186 patients (59%) in the 200 mg group, and 168 patients (59%) [corrected] in the 100 mg group achieved a PGA response, compared with 7 patients (4%) in the placebo group and 149 patients (48%) in the etanercept group (p<0·0001 for comparisons of both tildrakizumab groups vs placebo; p=0·0031 for 200 mg vs etanercept and p=0·0663 for 100 mg vs etanercept). Serious adverse events were similar and low in all groups in both trials. One patient died in reSURFACE 2, in the tildrakizumab 100 mg group; the patient had alcoholic cardiomyopathy and steatohepatitis, and adjudication was unable to determine the cause of death., Interpretation: In two phase 3 trials, tildrakizumab 200 mg and 100 mg were efficacious compared with placebo and etanercept and were well tolerated in the treatment of patients with moderate-to-severe chronic plaque psoriasis., Funding: Merck & Co., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Background: Adalimumab is indicated for the treatment of moderate to severe psoriasis in adults. We assessed the efficacy and safety of adalimumab in children and adolescents with severe plaque psoriasis., Methods: This randomised, double-blind, multiperiod, phase 3 trial was done at 38 clinics in 13 countries. Patients (aged ≥4 to <18 years) with severe plaque psoriasis who had not responded to topical therapy were randomly assigned with an interactive voice or web-response system (1:1:1) to receive adalimumab 0·8 mg/kg or 0·4 mg/kg subcutaneously at week 0, then every other week starting at week 1, or oral methotrexate once weekly (0·1-0·4 mg/kg) for 16 weeks. Randomisation was stratified by history of etanercept treatment, with a block size of three. Responders were withdrawn from treatment (for up to 36 weeks) and re-treated with adalimumab (for 16 weeks) if disease became uncontrolled. Ranked primary efficacy endpoints were the proportion of patients who achieved at least 75% improvement from baseline in Psoriasis Area and Severity Index (PASI75) score and clear or minimal physician global assessment (PGA) score at week 16, comparing adalimumab 0·8 mg/kg with methotrexate. Efficacy analysis was by intention to treat, and safety analysis included all patients who received at least one dose of study drug. This trial is registered with ClinicalTrials.gov, number NCT01251614, and has been completed., Findings: Between Dec 14, 2010, and Feb 5, 2015, 114 patients were randomly assigned to adalimumab 0·8 mg/kg (n=38), adalimumab 0·4 mg/kg (n=39) or methotrexate (n=37). At week 16, PASI75 was achieved in 22 (58%) of 38 patients in the adalimumab 0·8 mg/kg group compared with 12 (32%) of 37 patients in the methotrexate group (p=0·027). 23 (61%) of 38 patients in the adalimumab 0·8 mg/kg group and 15 (41%) of 37 in the methotrexate group achieved clear or minimal PGA (p=0·083). In the adalimumab 0·4 mg/kg group, 17 (44%) of 39 patients achieved PASI75 and 16 (41%) achieved clear or minimal PGA. The most frequent adverse events were infections (17 [45%] of 38 in the adalimumab 0·8 mg/kg group during initial treatment; 22 [56%] of 39 in the adalimumab 0·4 mg/kg group; 21 [57%] of 37 in the methotrexate group). Three serious adverse events were reported, all in patients in the adalimumab 0·4 mg/kg group, and were not judged to be related to study drug., Interpretation: Treatment with adalimumab 0·8 mg/kg in children and adolescents with severe plaque psoriasis provided significant improvements in PASI75 and a non-significant increase in the proportion of patients who achieved clear or minimal PGA compared with methotrexate. No new safety risks were identified., Funding: AbbVie., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Background: Secukinumab demonstrated superior efficacy to ustekinumab at week 4 and week 16 of the CLEAR study, with comparable safety, in subjects with moderate-to-severe plaque psoriasis., Objective: To compare the efficacy and safety of secukinumab and ustekinumab use over 52 weeks., Methods: Analysis of 52-week data from CLEAR, a randomized, double-blind, phase 3b study., Results: Among 676 randomized subjects, secukinumab demonstrated superiority to ustekinumab at week 52 in the proportion of subjects with ≥90% improvement in Psoriasis Area and Severity Index (PASI 90) (76% vs 61% [P < .0001]); PASI 100 responses were 46% versus 36% (P = .0103) and Investigator's Global Assessment responses of clear/almost clear skin were 80% versus 65% (P < .0001). Subjects on secukinumab reported greater reductions in psoriasis-related pain, itching, and scaling, and greater improvement across all quality-of-life measures evaluated (Dermatology Life Quality Index [DLQI], EuroQoL 5-Dimension Health Questionnaire, Work Productivity and Activity Impairment Questionnaire-Psoriasis, and Health Assessment Questionnaire-Disability Index). At week 52, 72% of subjects on secukinumab versus 59% on ustekinumab (P = .0008) reported no impact of skin disease on their lives (DLQI 0/1 response). Safety and tolerability was comparable., Limitations: There was no placebo arm., Conclusion: In this head-to-head, double-blind study, secukinumab demonstrated sustained superior efficacy in comparison with ustekinumab in clearing skin through week 52, greater improvement in quality of life, and a favorable and comparable safety profile., (Copyright © 2016 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)