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Background: Skin-infiltrating lymphocytes expressing type 1 cytokines have been linked to the pathophysiology of psoriasis. We evaluated the safety and efficacy of a human interleukin-12/23 monoclonal antibody in treating psoriasis.Methods: In this double-blind, placebo-controlled trial, 320 patients with moderate-to-severe plaque psoriasis underwent randomization to treatment with the interleukin-12/23 monoclonal antibody (one 45-mg dose, one 90-mg dose, four weekly 45-mg doses, or four weekly 90-mg doses) or placebo; 64 patients were randomly assigned to each group. Patients assigned to the interleukin-12/23 monoclonal antibody received one additional dose at week 16 if needed. Patients assigned to placebo crossed over to receive one 90-mg dose of interleukin-12/23 monoclonal antibody at week 20.Results: There was at least 75% improvement in the psoriasis area-and-severity index at week 12 (the primary end point) in 52% of patients who received 45 mg of the interleukin-12/23 monoclonal antibody, in 59% of those who received 90 mg, in 67% of those who received four weekly 45-mg doses, and in 81% of those who received four weekly 90-mg doses, as compared with 2% of those who received placebo (P<0.001 for each comparison), and there was at least 90% improvement in 23%, 30%, 44%, and 52%, respectively, of patients who received the monoclonal antibody as compared with 2% of patients who received placebo (P<0.001 for each comparison). Adverse events occurred in 79% of patients treated with the interleukin-12/23 monoclonal antibody as compared with 72% of patients in the placebo group (P=0.19). Serious adverse events occurred in 4% of patients who received the monoclonal antibody and in 1% of those who received placebo (P=0.69).Conclusions: This study demonstrates the therapeutic efficacy of an interleukin-12/23 monoclonal antibody in psoriasis and provides further evidence of a role of the interleukin-12/23 p40 cytokines in the pathophysiology of psoriasis. Larger studies are needed to determine whether serious adverse events might limit the clinical usefulness of this new therapeutic target. (ClinicalTrials.gov number, NCT00320216 [ClinicalTrials.gov].). [ABSTRACT FROM AUTHOR]

Erdheim-Chester disease (ECD) is a rare xanthomatous non-Langerhans cell histiocytosis which involves the marrow space of the long bones. Extraosseous sites most commonly affected include the eyes, lungs, pituitary glands, and kidneys. We report the case of a 49-year-old woman who presented with palpable breast nodules, followed by progressive soft tissue and subcutaneous disease, and involvement of the long bones, dysarthria, and dysphagia. The histopathologic features and skeletal radiography findings are consistent with ECD. This case represents an unusual presentation, which led to delayed diagnosis, as ECD of the breast has been rarely reported. ECD should be considered in the differential diagnosis of histiocytoid breast lesions, including fat necrosis and histiocytoid invasive mammary carcinoma. [ABSTRACT FROM AUTHOR]

We performed an analysis of toxicity and survival in stage III melanoma patients receiving adjuvant interferon alfa-2b (IFN). This was a retrospective single-arm analysis of 40 patients with stage III melanoma who received (IFN) administered at maximum tolerated doses of 20 mU/m2/day intravenously (i.v.) for 1 month and 10 mU/m2 three times per week subcutaneously (s.c.) for 48 weeks. Toxicity in our series is comparable to that experienced in the Eastern Cooperative Oncology Group (ECOG) 1684 trial, except for higher rates of dose-limiting myelosuppression and hepatotoxicity. All 40 patients experienced constitutional symptoms, but only 14/40 (35%) experienced grade 3 to 4 symptoms. Of the 40 patients, 36 (90%) experienced neurologic symptoms, but only seven (17.5%) experienced grade 3 to 4 neurotoxicity. Two patients stopped treatment because of severe psychiatric symptoms; one patient attempted suicide, and a psychosis developed in another. Thirty-nine (97.5%) patients experienced myelosuppression; 31 (77.5%) developing grade 3 to 4 myelosuppression. Hepatotoxicity was evident in 39 (97.5%) patients, and 26 (65%) experienced grade 3 to 4 hepatotoxicity. Three patients (7.5%) experienced mild renal toxicity. At a median follow-up of 27 months from initiation of therapy, there have been 19 relapses (47.5% disease-free survival [DFS]) and 10 deaths (75% OS) resulting from progression of disease. The DFS compares with the treatment arm in ECOG 1684 at 27 months, but overall survival is higher in our series of patients at the same time point. In a single program setting, IFN can be administered with similar side effects and outcome profiles seen in multi-institutional studies. Modifications in the induction regimen resulted in notably higher hematologic and hepatic toxicities but did not preclude administering further therapy and did not result in increased attrition rate among patients: only nine patients (22.5%) had their treatment stopped as a result of IFN-related toxicity. In comparison, 26% of patients had to have their treatment discontinued because of toxicity in ECOG 1684. [ABSTRACT FROM AUTHOR]

Tuberculosis (TB), caused by Mycobacterium tuberculosis, is a significant global health problem. In immunocompetent individuals, the microorganism can remain in a latent, non-contagious form, however, it may become active under conditions of immunosuppression. Tumour necrosis factor (TNF) inhibitors, which are frequently used for the management of immune-mediated disorders like psoriasis, have been associated with a significantly increased risk of reactivating latent TB. Consequently, international guidelines recommend TB screening and preventive treatment before starting anti-TNF therapy. These recommendations have extended to IL-12/23, IL-17, IL-23 and TYK2 inhibitors under a caution principle, despite their different mechanisms of action. However, current evidence suggests that some of these agents are arguably not associated with an increased risk of TB reactivation or development of TB disease after infection, which calls for a critical reassessment of these guidelines. We have conducted a literature search evaluating the risk of TB reactivation associated with these innovative therapies, integrating findings from both randomized clinical trials and real-world evidence. The identified evidence is limited but the low number of identified cases of reactivation with IL-17 and IL-23 inhibitors prompts reconsidering the need for preventive treatment for latent TB in all cases, regardless of biologic class or individual patient's risk of TB reactivation or drug toxicity. This review, along with the clinical insight of a panel of experts on behalf of the SPIN-FRT, led to the development of these consensus recommendations for managing psoriasis treatment in patients with latent TB infection or at risk of TB infection, who are receiving or are intended to receive biologic and non-biologic targeted therapies. These recommendations highlight the need for updates to the existing guidelines, aiming to provide a more differentiated approach that reflects the evolving landscape of psoriasis treatment and its implications for TB management., (© 2024 European Academy of Dermatology and Venereology.)

Background: Plaque psoriasis is a chronic, relapsing systemic illness that has a significant effect on quality of life. Bimekizumab is the first monoclonal antibody to target both interleukin (IL)-17A and IL-17F, and recently received Food and Drug Administration (FDA) approval for moderate to severe plaque psoriasis. Guidance is necessary regarding the safety of bimekizumab., Methods: A comprehensive literature search of PubMed, Scopus, and Google Scholar was completed for English-language original research articles on the safety of bimekizumab for moderate to severe psoriasis. A panel of 9 dermatologists and 1 rheumatologist with significant expertise in the treatment of psoriasis gathered to review the articles and create consensus statements on this new medication. A modified Delphi process was used to approve each statement, and strength of recommendation was assigned using the Strength of Recommendation Taxonomy criteria., Results: The literature search produced 110 articles that met the criteria. A thorough screening of the studies for relevance to the research question resulted in 15 articles. These were distributed to all panelists for review prior to a roundtable discussion. The panel unanimously voted to adopt 5 consensus statements and recommendations, all of which were given a strength of "A"., Conclusion: Bimekizumab has a safety profile consistent with other biologics, except for a higher risk of oral candidiasis. Its hepatic safety profile is comparable with other currently FDA-approved biologics for plaque psoriasis. In addition, the data do not support an association of bimekizumab with suicide, and the incidence of inflammatory bowel disease is not greater than the incidence of other IL-17 blockers. J Drugs Dermatol. 2024;23(8):592-599. doi:10.36849/JDD.8246.

Purpose: Atopic dermatitis (AD) adversely impacts quality of life (QoL). We evaluated the effect of upadacitinib, an oral selective Janus kinase inhibitor approved for moderate-to-severe AD, plus topical corticosteroids (+TCS) on patient-reported outcomes (PROs) over 52 weeks., Materials and methods: In the phase 3 AD Up study (NCT03568318), adults and adolescents with moderate-to-severe AD were randomized 1:1:1 to once-daily upadacitinib 15 mg, 30 mg, or placebo + TCS. Itch, skin pain/symptoms, sleep, QoL, daily activities, emotional state, mental health, and patient impressions of disease severity/improvement/treatment satisfaction were assessed., Results: This analysis included 901 patients. Within 1-2 weeks, PRO improvements were greater with both upadacitinib doses than with placebo ( p <.05). Improvements increased through weeks 4-8; rates were generally maintained through week 52. At week 52, the proportion of patients with clinically meaningful improvements in itch (Worst Pruritus Numerical Rating Scale improvement ≥4), skin pain (AD Symptom Scale Skin Pain improvement ≥4), sleep (AD Impact Scale [ADerm-IS] Sleep improvement ≥12), daily activities (ADerm-IS Daily Activities improvement ≥14), and emotional state (ADerm-IS Emotional State improvement ≥11) ranged from 62.1%-77.7% with upadacitinib 15 mg + TCS and 71.3%-83.6% with upadacitinib 30 mg + TCS., Conclusions: Upadacitinib + TCS results in rapid, sustained improvements in burdensome AD symptoms and QoL.

IL-23 is a cytokine produced by myeloid cells that drives the T helper 17 pathway and plays an essential role in the pathophysiology of plaque psoriasis. IL-23 activation initiates a cascade of cytokines subsequently inducing the expression of many psoriasis-related proteins. This study aimed to better understand the underlying mechanisms driving the differences between IL-23 and IL-17A blockade in patients with psoriasis and their implications for durability of clinical responses. Serum and/or skin biopsies were isolated from patients treated with guselkumab or secukinumab for evaluation of potential biomarkers of pharmacodynamic response to treatment. Guselkumab treatment led to significantly greater reductions of IL-17F and IL-22 serum levels than treatment with secukinumab at weeks 24 and 48, demonstrating sustained regulation of the IL-23/T helper 17 pathway. Analyses of proteomic and transcriptomic profiles of patient sera and skin biopsies demonstrated differential regulation of proteins involved in chemokine, TNF, and relevant immune signaling pathways to a greater degree with guselkumab than with secukinumab treatment. These data provide insights into the differences between the mechanisms and impact of IL-23 and IL-17A blockade in psoriasis, with implications for efficacy observations and treatment paradigms. Trial Registration: The original study was registered at ClinicalTrials.gov (NCT03090100)., (© 2024 The Authors.)

Secukinumab is a fully human IgG1 antibody that selectively binds to and neutralizes the proinflammatory cytokine interleukin-17A. Secukinumab is an effective and well-tolerated treatment for plaque psoriasis. There is a limited real-word evidence for dose optimisation of secukinumab based on clinical response. PURE is a multi-national, prospective, observational study in patients with moderate to severe chronic plaque psoriasis in Canada and Latin America, assessing the real-world safety and effectiveness of secukinumab and other indicated therapies. The aim of the current snapshot analysis was to evaluate the effectiveness and safety of on-label dose and updosed secukinumab in patients with plaque psoriasis enrolled in the PURE study. At the time of analysis, 676 patients received secukinumab, of which 84.6% (n = 572) remained on the on-label dose, while 15.4% (n = 104) were updosed. With on-label secukinumab, the absolute Psoriasis Area and Severity Index (PASI) score was reduced from 13.6 at baseline to 1.2 over 36 months, with treatment persistence of 73% at 40 months. At Month 36, 73.2% of the patients receiving on-label secukinumab achieved Investigator's Global Assessment (IGA) 0/1. With updosed secukinumab (300 mg every 2 weeks, 300 mg every 3 weeks, 450 mg every 4 weeks, or 450 mg every 3 weeks), 57.9% of the patients showed improvement in the absolute PASI score at the first visit after updosing, with treatment persistence of 50% at 12 months after updosing. At Month 15, 40% of patients receiving updosed secukinumab achieved IGA 0/1. Patients with previous biologic exposure (odds ratio [OR]: 3.25; 95% confidence interval [CI]: 2.03, 5.18, p < 0.0001) were more likely to be updosed while those with a body weight < 90 kg (OR: 0.49; 95% CI [0.31, 0.77], p = 0.0019) were less likely to be updosed. Previous biologic exposure (HR [hazard ratio]: 1.47; 95% CI [1.24, 1.75], p < 0.0001) and current biologic exposure (secukinumab vs. other indicated therapies: HR 0.57; 95% CI [0.43, 0.75], p = 0.0001) were significantly associated with time to secukinumab updosing. No new or unexpected safety signals were observed with updosed secukinumab. Secukinumab updosing was efficacious and well-tolerated in patients with psoriasis who failed to respond to the approved on-label regimen, suggesting that updosing may be a useful therapeutic option for approved dose non-responders., (© 2024. The Author(s).)

Background: Psoriasis is an immune-mediated inflammatory disease characterized by activation of IL-23-driven IL-17-producing T cell and other IL-23 receptor-positive IL-17-producing cell responses. Selective blockade of IL-23p19 with guselkumab was superior to blockade of TNF-α with adalimumab (ADA) in treating moderate-to-severe psoriasis. Objective: Pharmacodynamic responses of guselkumab versus ADA were compared in patients with psoriasis in VOYAGE 1., Design: Inflammatory cytokine serum levels were assessed (n = 118), and lesional and nonlesional skin biopsies were collected (n = 38) in patient subsets at baseline and 4, 24, and 48 weeks after treatment to evaluate pharmacodynamic responses of guselkumab versus those of ADA., Results: Guselkumab provided rapid reductions in serum IL-17A, IL-17F, and IL-22 levels by week 4 versus at baseline, which were maintained through weeks 24 and 48 ( P < .001). The magnitude of reduction of IL-17A and IL-22 at week 48 and IL-17F at weeks 4, 24, and 48 were greater with guselkumab than with ADA (all P < .05). In the skin, guselkumab reduced the expression of IL-23/IL-17 pathway-associated and psoriasis-associated genes., Conclusion: These data provide extensive characterization of pharmacodynamic anti-inflammatory responses to IL-23p19 and TNF-α inhibition in human blood and tissue over time with FDA-approved doses of guselkumab and ADA. Trial registration: ClinicalTrials.govClinicalTrials.gov (NCT02207231)., (© 2024 The Authors.)

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: Orismilast is a novel oral phosphodiesterase-4 (PDE4) B/D inhibitor being investigated as a potential treatment for moderate-to-severe psoriasis., Objective: To evaluate efficacy and safety of orismilast modified-release formulation in moderate-to-severe psoriasis., Methods: This multicenter, randomized (1:1:1:1 to 20, 30, 40 mg orismilast or placebo, twice daily), double-blinded, placebo-controlled, parallel-group, phase 2b, 16-week, dose-ranging study evaluated orismilast in adults with moderate-to-severe plaque psoriasis (NCT05190419). Efficacy end points were analyzed using multiple imputation., Results: Of 202 randomized patients, baseline characteristics were balanced across arms, except greater severe disease proportions for orismilast vs placebo. Orismilast showed significant improvements in the primary end point, percentage change in Psoriasis Area and Severity Index (PASI), from baseline to week 16 (orismilast -52.6% to -63.7% and placebo, -17.3%; all P <.001). Greater proportions receiving orismilast achieved PASI75 (39.5%-49.0%; P <.05) and PASI90 (22.0%-28.3%; P <.05 for 20 and 40 mg) vs placebo (PASI75, 16.5% and PASI90, 8.3%) at week 16. Safety findings were as expected with PDE4 inhibition; dose-dependent tolerability effects observed., Limitations: Small sample size, disease severity imbalance between groups, limited duration and diversity in study population., Conclusion: Orismilast demonstrated greater efficacy vs placebo and a safety profile in line with PDE4 inhibition., Competing Interests: Conflicts of interest Dr Warren has received research grants from AbbVie, Almirall, Amgen, Celgene, Janssen, Lilly, Leo Pharma, Novartis, Pfizer, and UCB, and consulting fees from AbbVie, Almirall, Amgen, Arena, Astellas, Avillion, Biogen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, DiCE, GlaxoSmithKline, Janssen, Lilly, Leo Pharma, Novartis, Pfizer, Sanofi, Sun Pharma, UCB, and UNION therapeutics. Dr French has received consulting fees and/or honoraria from AbbVie, AC Immune, Almirall, Amgen, Biotest, Eli Lilly, Galderma, InflaRx, Janssen, Leo Pharma, Novartis, Regeneron, UCB, UNION therapeutics, and Vaderis Therapeutics, and has served as president of the International League of Dermatological Societies. Dr Blauvelt has received research grants from AbbVie, Acelyrin, Allakos, Almirall, Alumis, Amgen, Arcutis, Athenex, Boehringer Ingelheim, Bristol Myers Squibb, Concert, Dermavant, Eli Lilly, Evelo, Evommune, Galderma, Incyte, Janssen, Leo Pharma, Merck, Novartis, Pfizer, Regeneron, Sanofi, Sun Pharma, UCB Pharma, and Ventyx, and honoraria from 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, Escient, Evelo, Evommune, Forte, Galderma, HighlightII Pharma, Incyte, InnoventBio, Janssen, Landos, Leo Pharma, Lipidio, Merck, Monte Rosa Therapeutics, Nektar, Novartis, Overtone Therapeutics, Pfizer, Rani, Rapt, Regeneron, Sanofi, Sanofi Genzyme, Spherix Global Insights, Sun Pharma, Takeda, TLL Pharmaceutical, TrialSpark, UCB Pharma, UNION therapeutics, Ventyx, Vibliome, and Xencor. Dr Langley has received honoraria from AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Dermavant, Dermira, Eli Lilly, GlaxoSmithKline, Janssen, Leo Pharma, Novartis, Ortho Dermatologics, Pfizer, Sanofi Genzyme, Sun Pharma, and UCB. Dr Egeberg has received research grants from AbbVie, Danish National Psoriasis Foundation, Eli Lilly, Janssen, Kgl Hofbundtmager Aage Bangs Foundation, Novartis, Pfizer, Boehringer Ingelheim, and Simon Spies Foundation, and consulting fees and/or honoraria and/or travel bursaries from AbbVie, Almirall, Boehringer Ingelheim, Bristol Myers Squibb, Dermavant, Eli Lilly, Galderma, Galapagos NV, Horizon Therapeutics, Janssen, Leo Pharma, Mylan, Novartis, Pfizer, Samsung Bioepis Co Ltd, UCB, and UNION therapeutics. Dr Mrowietz has received honoraria from UNION therapeutics. Dr Hunter has received grant funding from Janssen, Merck Serono, and Pfizer, honoraria and/or consultancy fees and/or travel bursaries from AbbVie, Almirall, DICE Therapeutics, Eli Lilly, Janssen, La Roche-Posay, Leo Pharma, Novartis, Regeneron, Sanofi Genzyme, UCB, and UNION therapeutics, and has acted as an investigator for AbbVie, Almirall, Bayer Pharmaceuticals, DICE Therapeutics, Eli Lilly, Evelo Biosciences Inc, Janssen, Leo Pharma, Novartis, ONO Pharmaceutical Co Ltd, Sanofi Genzyme, UCB, and UNION therapeutics. Dr Gooderham has received research grants from AbbVie, Akros Pharma Inc, Amgen, Arcutis Pharmaceuticals Inc, Asana Bio Sciences, AnaptysBio, Aristea, Bausch Health, Boehringer Ingelheim International, Bristol Myers Squibb, Celgene, Coherus Biosciences, Dermavant, Dermira, Eli Lilly, Galderma, GlaxoSmithKline, Incyte, Janssen, Kyowa Kirin, Leo Pharma, MedImmune, Merck, Meiji, Moonlake, Novartis, Nimbus Therapeutics, Pfizer, Regeneron, Reistone, Sanofi Genzyme, Sun Pharma, Tarsus, Takeda, UCB, and Ventyx, consulting fees and/or honoraria and/or travel bursaries from AbbVie, Akros Pharma, Amgen, Arcutis Pharmaceuticals Inc, Bausch Health, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, Galderma, GlaxoSmithKline, Janssen, Leo Pharma, Novartis, Pfizer, Regeneron, Sanofi Genzyme, Sun Pharma, UCB, and UNION therapeutics, and is the owner of a phototherapy center. Author Soerensen is an employee of UNION therapeutics. Dr Andres has received consulting fees from UNION therapeutics. Dr Sommer is an employee and shareholder of UNION therapeutics, received consulting fees from UNION therapeutics, patents with UNION therapeutics, and serves as a board member of UNION therapeutics. Author Carlsson is an employee of UNION therapeutics. Dr Kjøller is an employee of and shareholder in UNION therapeutics, and serves as chairman of the Danish Life Science Cluster. Strober has received consulting fees and/or honoraria from AbbVie, Alamar, Almirall, Alumis, Amgen, Arcutis, Arena, Aristea, Asana, Boehringer Ingelheim, Bristol Myers Squibb, Capital One, Connect Biopharma, CorEvitas, Dermavant, Eli Lilly, Evelo Biosciences, Immunic Therapeutics, Incyte, Janssen, Kangpu Pharmaceuticals, Leo Pharma, Maruho, Meiji Seika Pharma, Mindera Health, Nimbus, Novartis, Pfizer, Protagonist, Regeneron, Sanofi Genzyme, Sun Pharma, UCB, UNION therapeutics, Ventyxbio, and vTv Therapeutics, shareholder in Connect Biopharma, and Mindera Health, serves as scientific codirector of CorEvitas Psoriasis Registry, and serves as editor-in-chief of the Journal of Psoriasis and Psoriatic Arthritis., (Copyright © 2023 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Competing Interests: Dr Langley has received honoraria as a principal investigator, scientific advisor, or speaker for AbbVie, Amgen, Boehringer Ingelheim, Bristol-Myers-Squibb, Dermavant, Dermira, Eli Lilly, GlaxoSmithKline, Janssen, Leo Pharma, Novartis, Ortho Dermatologics, Pfizer, Sanofi -Genzyme, Sun Pharma, and UCB Pharma. Drs Sanyal, Disher, and Patel and Author Situ are employees of EVERSANA, which received funding from Janssen Research and Development for this study. Authors Alulis, Hassan, Peterson, and Lee and Dr Teneralli are employees of Janssen Research and Development.

Introduction: Early detection of melanoma requires timely access to medical care. In this study, we examined the feasibility of using artificial intelligence (AI) to flag possible melanomas in self-referred patients concerned that a skin lesion might be cancerous., Methods: Patients were recruited for the study through advertisements in 2 hospitals in Halifax, Nova Scotia, Canada. Lesions of concern were initially examined by a trained medical student and if the study criteria were met, the lesions were then scanned using the FotoFinder System ® . The images were analyzed using their proprietary computer software. Macroscopic and dermoscopic images were evaluated by 3 experienced dermatologists and a senior dermatology resident, all blinded to the AI results. Suspicious lesions identified by the AI or any of the 3 dermatologists were then excised., Results: Seventeen confirmed malignancies were found, including 10 melanomas. Six melanomas were not flagged by the AI. These lesions showed ambiguous atypical melanocytic proliferations, and all were diagnostically challenging to the dermatologists and to the dermatopathologists. Eight malignancies were seen in patients with a family history of melanoma. The AI's ability to diagnose malignancy is not inferior to the dermatologists examining dermoscopic images., Conclusion: AI, used in this study, may serve as a practical skin cancer screening aid. While it does have technical and diagnostic limitations, its inclusion in a melanoma screening program, directed at those with a concern about a particular lesion would be valuable in providing timely access to the diagnosis of skin cancer., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

For decades, topical corticosteroids have been the mainstay of treatment for mild-to-moderate inflammatory skin diseases, even though only short-term use is approved for these agents and systemic inflammation is not addressed. Increased understanding of the immunopathogenesis of these conditions, especially for psoriasis and atopic dermatitis, has facilitated the development of antibody-based drugs that neutralize single key cytokines or their associated receptors, such as interleukin (IL)-17A/F, IL-23, and IL-17RA in psoriasis and IL-13 and IL-4Rα in atopic dermatitis. However, oral therapy is still preferred by many patients owing to the ease of use and needle-free administration. Phosphodiesterase 4 (PDE4) inhibitors have been approved for both oral and topical use for inflammatory skin diseases. In this review, we present a summary of an emerging class of selective PDE4B/D inhibitors under clinical development and compare the differences in selectivity of this new generation of PDE4 inhibitors with the less selective currently approved PDE4 inhibitors., (© 2023. The Author(s).)

Interleukin (IL)-23-independent IL-17A production has been suggested to be involved in persistent manifestations of psoriatic disease, including anti-IL-12/23-refractory psoriatic plaques; this study aimed to test this hypothesis by investigating the clinical and molecular effects of direct IL-17A (with secukinumab) versus selective IL-23 inhibition (with guselkumab) in patients with anti-IL-12/23 (ustekinumab)-refractory psoriatic plaques. A 16-week, randomized, open-label, parallel-group, Phase IIa study (ARROW, NCT03553823) was conducted in patients with ≥1 active psoriatic plaque (total clinical score [TCS] ≥6) at screening despite treatment with ustekinumab, and a Psoriasis Area and Severity Index (PASI) score 1-10. Patients were randomized 1:1 to receive secukinumab 300 mg (n = 20) or guselkumab 100 mg (n = 20). Biopsies from one refractory ('target plaque') were obtained at baseline and Week 16. The primary endpoint was the proportion of patients whose ustekinumab-refractory target plaque achieved clear/almost clear status (TCS 0-2) at Week 16. Transcriptomic and histological analyses were conducted on target plaques to determine the molecular effects of direct IL-17A versus selective IL-23 inhibition. At Week 16, target plaque clear/almost clear status was achieved in 60.0% of patients treated with secukinumab versus 40.0% of patients treated with guselkumab (p = 0.1715). Molecular analyses identified that secukinumab modulated a greater proportion of psoriasis disease transcriptome genes (72.1% vs. 48.0%) and resulted in more histological responders (72.2% vs. 53.3%) compared with guselkumab. Secukinumab demonstrated a greater clinical and molecular effect on ustekinumab-refractory psoriatic plaques versus guselkumab. These results are consistent with the hypothesis that IL-23-independent IL-17 mechanisms may be relevant to the inflammation driving refractory manifestations of psoriasis., (© 2023 The Authors. Experimental Dermatology published by John Wiley & Sons Ltd.)

Background: Risankizumab and guselkumab, inhibitors of the interleukin (IL)-23 p19 subunit, are approved for treatment of adult patients with moderate-to-severe plaque psoriasis, and both have shown superiority over placebo in randomised clinical trials. Both agents have also shown superiority to the IL-17 inhibitor secukinumab at different timepoints. We investigated the efficacy and safety of the IL-23 p19 inhibitor mirikizumab versus placebo and secukinumab for patients with moderate-to-severe plaque psoriasis., Methods: OASIS-2 was a phase 3, multicentre, randomised, double-blind trial. We recruited participants aged at least 18 years who had a confirmed diagnosis of chronic plaque psoriasis for at least 6 months before baseline that involved at least 10% of body surface area (BSA), an absolute Psoriasis Area and Severity Index (PASI) score of at least 12, and a Static Physician's Global Assessment (sPGA) score of at least 3 at both the screening and baseline visits. We excluded patients who had an uncontrolled or unstable health condition at screening. We randomly assigned patients (4:4:4:1) to receive 250 mg mirikizumab every 4 weeks for 16 weeks (induction) then every 8 weeks from week 16 to week 52 (maintenance); 250 mg mirikizumab every 4 weeks for 16 weeks, then 125 mg mirikizumab every 8 weeks from week 16 to 52; 300 mg secukinumab once weekly up to week 4, then every 4 weeks thereafter; or placebo every 4 weeks for 16 weeks, followed by 250 mg mirikizumab every 4 weeks from week 16 to 32 and then every 8 weeks from week 32 to 52. The primary outcome was superiority of mirikizumab (250 mg induction dose) versus placebo at week 16, assessed as the proportion of patients with an sPGA score of 0 or 1 with an improvement from baseline of at least 2 points, and the proportion of patients with at least 90% improvement from baseline in PASI score (PASI 90), in the intention-to-treat-population. We assessed safety in all randomly assigned participants who received at least one dose of mirikizumab until week 16 (induction safety population) and all randomly assigned participants who received at least one dose of mirikizumab or secukinumab until week 52 (active treatment safety population). This trial is registered at ClinicalTrials.gov, NCT03535194, and is completed., Findings: Between June 26, 2018, and April 2, 2019, we screened 1738 participants, of whom 1465 (84·3%) were enrolled. The mean age of participants was 46·0 years (SD 13·8), 1000 (68·3%) were men, 465 (31·7%) were women, and 1195 (81·6%) were White. Participants were randomly assigned to receive mirikizumab 250 mg for induction and maintenance (n=454 [31·0%]), mirikizumab 250 mg for induction and 125 mg for maintenance (n=451 [30·8%]), secukinumab 300 mg (n=448 [30·6%]), or placebo followed by mirikizumab (n=112 [7·6%]). Baseline characteristics were similar across treatment groups. At week 16, 721 (79·7% [95% CI 77·0-82·3]) of 905 participants in the mirikizumab 250 mg induction groups had an sPGA score of 0 or 1 versus seven (6·3% [1·8-10·7]) of 112 participants in the placebo group (p<0·0001 for superiority). At week 16, 673 (74·4% [71·5-77·2]) of 905 participants in the mirikizumab groups had PASI 90 compared with seven (6·3% [1.8-10.7]) in the placebo group (p<0·0001 for superiority). Treatment-emergent adverse events were reported with similar frequency across treatment groups during weeks 0-52. Four major adverse cardiovascular events were reported in the mirikizumab groups versus none in the placebo and secukinumab groups up to week 16, with one fatal acute myocardial infarction in a patient treated with mirikizumab, which the investigator considered to be related to the study drug., Interpretation: This trial showed superiority of mirikizumab at a dose of 250 mg over placebo in patients with moderate-to-severe plaque psoriasis, with a safety profile consistent with that of the IL-23 class. The study sponsor is not pursuing licensing of mirikizumab in this patient population because of a reprioritised development strategy with a focus on gastrointestinal-related indications., Funding: Eli Lilly and Company., Competing Interests: Declaration of interests KP reports grants from AbbVie, Akros, Amgen, Anacor, Arcutis, Astellas, Avillion, Bausch Health/Valeant, Baxalta, Boehringer Ingelheim, Bristol Myers Squibb, Can-Fite Biopharma, Celgene, Coherus, Dermavant, Dermira, Dow Pharma, Eli Lilly and Company, Evelo, Galapagos, Galderma, Genentech, Gilead, GSK, Incyte, Janssen, Kyowa Hakko Kirin, Leo, Medimmune, MSD, Merck Serono, Moberg Pharma, Novartis, Pfizer, PRCL Research, Regeneron, Roche, Sanofi-Aventis/Genzyme, Sun Pharma, Takeda, and UCB; consulting fees from AbbVie, Akros, Amgen, Arcutis, Astellas, Avillion, Bausch Health/Valeant, Baxalta, Boehringer Ingelheim, Bristol Myers Squibb, Can-Fite Biopharma, Celgene, Coherus, Dermavant, Dermira, Dice, Dow, Eli Lilly and Company, Evelo, Galapagos, Galderma, Genentech, Incyte, Janssen, Kyowa Hakko Kirin, Leo, Meiji Seika Pharma, MSD, Merck Serono, Mitsubishi Pharma, Novartis, Pfizer, PRCL Research, Regeneron, Roche, Sanofi-Aventis/Genzyme, Takeda, and UCB; speaker's bureau OR honoraria from Abbvie, Akros, Amgen, Astellas, Bausch Health/Valeant, Boehringer Ingelheim, Celgene, Coherus, Eli Lilly and Company, Galderma, Incyte, Janssen, Kyowa Hakko Kirin, Leo, MSD, Merck Serono, Mitsubishi Pharma, Novartis, Pfizer, PRCL Research, Sanofi-Aventis/Genzyme, Takeda, and UCB; and serving on advisory boards, steering committees, OR acting as scientific officer for AbbVie, Akros, Amgen, Anacor, Arcutis, Astellas, Bausch Health/Valeant, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Dice, Dow Pharma, Eli Lilly and Company, Galderma, Janssen, Kyowa Hakko Kirin, MSD, Merck Serono, Novartis, Pfizer, Regeneron, Sanofi-Aventis/Genzyme, Sun Pharmaceutical Industries, and UCB. RBW reports grants or contracts from AbbVie, Almirall, Amgen, Celgene, Janssen, Eli Lilly and Company, Leo, Medac, Novartis, Pfizer, and UCB; and consulting fees from AbbVie, Almirall, Amgen, Arena, Astellas, Avillion, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, DiCE, GSK, Janssen, Eli Lilly and Company, Leo, Medac, Novartis, Pfizer, Sanofi, Sun Pharmaceutical Industries, UCB, and UNION. LG reports research grants from Eli Lilly and Company; and leadership or fiduciary roles with the National Psoriasis Foundation (Board of Directors and Research Committee Chair) and the American Academy of Dermatology (Board of Directors). KR has served as adviser or paid speaker for or participated in clinical trials sponsored by Abbvie, Almirall, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Forward Pharma, Gilead, Galderma, Janssen-Cilag, Kyowa Kirin, Leo, Lilly, Medac, Novartis, Ocean Pharma, Pfizer, Sanofi, and UCB; and is co-founder of Moonlake Immunotherapeutics. RGL has been a principal investigator for AbbVie, Amgen, Boehringer Ingelheim, Celgene, Eli Lilly and Company, Leo, Merck, Novartis, Pfizer, and UCB; reports speaker's bureau or honoraria from AbbVie, Amgen, Celgene, Eli Lilly and Company, Leo, Merck, Novartis, and Pfizer; and serving on scientific advisory boards for AbbVie, Amgen, Boehringer Ingelheim, Celgene, Eli Lilly and Company, Leo, Merck, Novartis, Pfizer, and UCB. CP reports consulting fees from Almirall, Amgen, AbbVie, Boehringer Ingelheim, Celgene, Galderma, Eli Lilly and Company, Novartis, Janssen, Sandoz, Pierre Fabre, Pfizer, LEO Pharma, Merck, Regeneron, Sanofi, and UCB. AA reports consulting fees from AbbVie and Janssen; and honoraria for lectures from AbbVie, Celgene, Eisai, Eli Lilly and Company, Janssen, Kyowa Kirin, LEO Pharma, Maruho, Mitsubishi Pharma, Pfizer, Sun Pharma, Taiho Pharma, Torii Pharmaceutical, and UCB Pharma. LJ, VA, and OO are employees and shareholders of Eli Lilly and Company. ML reports grants or contracts from Abbvie, Amgen, Arcutis, Avotres, Boehringer Ingelheim, Dermavant Sciences, Eli Lilly and Company, Incyte, Janssen Research & Development, Ortho Dermatologics, Regeneron, and UCB; and consulting fees from Aditum Bio, Almirall, AltruBio, AnaptysBio, Arcutis, Aristea Therapeutics, Arrive Technologies, Avotres Therapeutics, BiomX, Boehringer-Ingelheim, Bristol-Myers Squibb, Cara Therapeutics, Castle Biosciences, Corrona, Dermavant Sciences, Dr Reddy's Laboratories, Evelo Biosciences, Evommune, Facilitatation of International Dermatology Education, Forte Biosciences, Foundation for Research and Education in Dermatology, Helsinn Therapeutics, Hexima, LEO Pharma, Meiji Seika Pharma, Mindera, Pfizer, Seanergy, and Verrica., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: Malignancy risk surveillance among patients receiving long-term immunomodulatory psoriasis treatments remains an important safety objective., Objective: To report malignancy rates in patients with moderate-to-severe psoriasis treated with guselkumab for up to 5 years versus general and psoriasis patient populations., Methods: Cumulative rates of malignancies/100 patient-years (PY) were evaluated in 1721 guselkumab-treated patients from VOYAGE 1 and 2. Malignancy rates (excluding nonmelanoma skin cancer [NMSC]) were compared with rates in the Psoriasis Longitudinal Assessment and Registry. Standardized incidence ratios comparing malignancy rates (excluding NMSC and cervical cancer in situ) between guselkumab-treated patients and the general US population using Surveillance, Epidemiology, and End Results data were calculated, adjusting for age, sex, and race., Results: Of 1721 guselkumab-treated patients (>7100 PY), 24 had NMSC (0.34/100PY; basal:squamous cell carcinoma ratio, 2.2:1), and 32 had malignancies excluding NMSC (0.45/100PY). For comparison, the malignancy rate excluding NMSC was 0.68/100PY in the Psoriasis Longitudinal Assessment and Registry. Malignancy rates (excluding NMSC/cervical cancer in situ) in guselkumab-treated patients were consistent with those expected in the general US population (standardized incidence ratio = 0.93)., Limitations: Inherent imprecision in determining malignancy rates., Conclusions: In patients treated with guselkumab for up to 5 years, malignancy rates were low and generally consistent with rates in general and psoriasis patient populations., Competing Interests: Conflicts of interest Dr Blauvelt has served as a speaker (received honoraria) for AbbVie, Bristol Myers Squibb, Eli Lilly and Company, Pfizer, Regeneron, and Sanofi, served as a scientific advisor (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 and Company, 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 acted as a clinical study investigator (institution has received clinical study funds) for AbbVie, Acelyrin, Almirall, Alumis, Amgen, Arcutis, Athenex, Boehringer Ingelheim, Bristol Myers Squibb, Concert, Dermavant, Eli Lilly and Company, Evelo, Evommune, Galderma, Incyte, Janssen, Leo, Merck, Novartis, Pfizer, Regeneron, Sun Pharma, and UCB Pharma. Dr Lebwohl 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, LLC, Ortho Dermatologics, Regeneron, and UCB, Inc, and is a consultant for Aditum Bio, Almirall, AltruBio Inc., AnaptysBio, Arcutis, Inc, Arena Pharmaceuticals, Aristea Therapeutics, Arrive Technologies, Avotres Therapeutics, BiomX, Brickell Biotech, Boehringer Ingelheim, Bristol Myers Squibb, Cara Therapeutics, Castle Biosciences, CorEvitas, Dermavant Sciences, 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. Dr Langley has served, and has received compensation in the form of grant funding and/or honoraria, as principal investigator for and is on the scientific advisory board or 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. Ms Rowland and Dr Chan are employees of Janssen Scientific Affairs, LLC (a subsidiary of Johnson & Johnson), and own Johnson & Johnson stock/stock options. Dr Yang is an employee of Janssen Pharmaceutical Companies of Johnson & Johnson and owns Johnson & Johnson stock/stock options. Ms Miller, Ms You, and Dr Yu are employees of Janssen Research & Development, LLC (a subsidiary of Johnson & Johnson), and own Johnson & Johnson stock/stock options. Dr Thaçi 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, Janssen, Kyowa Hakko Kirin, LEO Pharma, Merck Sharp & Dohme, Morphosys, Novartis, Pfizer, Regeneron Pharmaceuticals, Sandoz-Hexal, Sanofi, and UCB, and has received research grants from LEO Pharma and Novartis. Dr Foley has received grant support, and/or served on advisory boards, and/or served as a consultant, and/or has received travel grants, and/or has served as a speaker for or received honoraria from AbbVie, Akaal, Amgen, Arcutis, Argenx, Aslan, AstraZeneca, Boehringer Ingelheim, Botanix, Bristol Myers Squibb, Celgene, Celtaxsys, CSL, Cutanea, Dermira, Evelo, Galderma, GenesisCare, Genentech, GlaxoSmithKline, Hexima, Janssen, Kymab, Leo Pharma, Lilly, Mayne Pharma, MedImmune, Melaseq/Geneseq, Merck, Novartis, Pfizer, Regeneron, Reistone, Roche, Sanofi, Sun Pharma, Teva, UCB Pharma, and Valeant. Dr Papp has received clinical research grants from, honoraria from, and/or served as a consultant, scientific advisor, investigator, speaker, and/or medical officer for AbbVie, Akros, Amgen, Anacor, Arcutis, Astellas, Avillion, Bausch Health, Baxalta, Boehringer Ingelheim, Bristol Myers Squibb, Can-Fite Biopharma, Celgene, Celltrion, Coherus, Dermavant, Dermira, Dice Pharmaceuticals, Dow Pharma, Eli Lilly, Evelo, Galapagos, Galderma, Genentech, Gilead, GlaxoSmithKline, Incyte, Janssen, Kyowa Hakko Kirin, LEO Pharma, Medimmune, Meiji Seika Pharma, Merck Sharpe & Dohme, Merck-Serono, Mitsubishi Pharma, Moberg Pharma, Novartis, Pfizer, PRCL Research, Regeneron, Reistone, Roche, Sandoz, Sanofi-Aventis/Genzyme, Sun Pharma, Takeda, UCB Pharma, Valeant, vTv Therapeutics, and Xenocor., (Copyright © 2023 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

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: Given the chronic nature of psoriasis and the loss of response that can be observed with therapies over time, it is important to understand the long-term efficacy of new treatments., Objectives: To evaluate maintenance of Week 16 responses with bimekizumab (BKZ) treatment through Year 3, in patients with moderate-to-severe plaque psoriasis., Methods: Data were pooled from BKZ-treated patients in the 52-week (BE VIVID) and 56-week (BE READY and BE SURE) phase III studies, and their ongoing open-label extension (OLE), BE BRIGHT. Efficacy outcomes are reported through 3 years of BKZ treatment in patients with an efficacy response at Week 16. Missing data were imputed primarily using modified nonresponder imputation (mNRI), with nonresponder imputation and observed case data also reported., Results: A total of 989 patients were randomized to BKZ at baseline in BE VIVID, BE READY and BE SURE. At Week 16, 693 patients achieved ≥ 90% reduction from baseline in Psoriasis Area and Severity Index (PASI 90), 503 achieved 100% reduction from baseline in PASI (PASI 100), 694 achieved absolute PASI ≤ 2 and 597 achieved body surface area (BSA) ≤ 1%, and continued into the OLE. Of these, 93.0% maintained PASI 90, 80.8% maintained PASI 100, 94.0% maintained PASI ≤ 2 and 90.3% maintained BSA ≤ 1% responses through to 3 years of BKZ treatment (mNRI). Among Week 16 PASI 90 responders, 96.8% and 72.5% also achieved Investigator's Global Assessment 0/1 and PASI 100 at Week 16, respectively, and 92.2% and 73.4% achieved these responses at Year 3 (mNRI). Among Week 16 PASI 100 responders, 76.3% also achieved Dermatology Life Quality Index (DLQI) 0/1 at Week 16, and DLQI 0/1 response increased with continuous BKZ treatment to 89.0% at Year 3 (mNRI)., Conclusions: High levels of clinical response were maintained through to 3 years of BKZ treatment in the vast majority of Week 16 responders. Long-term treatment with BKZ was efficacious, with important benefits for health-related quality of life, in patients with moderate-to-severe plaque psoriasis., Competing Interests: Conflicts of interest B.S.: Consultant (honoraria) from AbbVie, 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, Sun Pharma, UCB Pharma, Union Therapeutics, Ventyxbio and vTv Therapeutics; Stock options in Connect Biopharma and Mindera Health; Speaker for AbbVie, Eli Lilly, Janssen, Regeneron and Sanofi; Scientific Co-Director (consulting fee) from CorEvitas (formerly Corrona) Psoriasis Registry; Investigator for AbbVie, Cara Therapeutics, CorEvitas Psoriasis Registry, Dermavant, Dermira and Novartis; Editor-in-Chief (honorarium) of Journal of Psoriasis and Psoriatic Arthritis. Y.T.: Honoraria and/or grants from AbbVie, Boehringer Ingelheim, Bristol Myers Squibb, Eisai, Eli Lilly, Janssen, Kyowa Hakko Kirin, LEO Pharma, Maruho, Mitsubishi Tanabe Pharma, Sun Pharma, Taiho Pharmaceutical, Torii Pharmaceutical and UCB Pharma. U.M.: Served as advisor and/or clinical study investigator for, and/or received honoraria and/or grants from AbbVie, Almirall, Aristea, Boehringer Ingelheim, Celgene, Dr Reddy’s Laboratories, Eli Lilly, Foamix, Formycon, Forward Pharma, Janssen, LEO Pharma, Medac, Novartis, Phi-Stone, Pierre Fabre, Sanofi and UCB Pharma. M.L.: Employee of Mount Sinai and receives research funds from AbbVie, Amgen, Arcutis, Avotres Therapeutics, Boehringer Ingelheim, Cara Therapeutics, Dermavant, Eli Lilly, Incyte, Janssen, LLC, Ortho Dermatologics, Regeneron and UCB Pharma; Consultant for Aditum Bio, Almirall, AltruBio, AnaptysBio, Arcutis, Aristea, Arrive Technologies, Avotres Therapeutics, BiomX, Boehringer Ingelheim, Bristol Myers Squibb, Cara Therapeutics, Castle Biosciences, CorEvitas (formerly Corrona), Dermavant, Dr Reddy’s Laboratories, Evelo Biosciences, Evommune, Facilitation of International Dermatology Education, Forte Biosciences, Foundation for Research and Education in Dermatology, Helsinn Therapeutics, Hexima, LEO Pharma, Meiji Seika Pharma, Mindera Health, Pfizer, Seanergy and Verrica. P.F.: Grant support from AbbVie, Amgen, Bristol Myers Squibb, Celgene, Eli Lilly, Janssen, LEO Pharma, Merck, Novartis, Pfizer, Sanofi and Sun Pharma; Investigator for AbbVie, Akaal, Amgen, Arcutis, Argenx, Aslan, AstraZeneca, Boehringer Ingelheim, Botanix, Bristol Myers Squibb, Celgene, Celtaxsys, CSL, Cutanea, Dermira, Eli Lilly, Evelo Biosciences, Galderma, Genentech, Geneseq, GenesisCare, GSK, Hexima, Janssen, Kymab, LEO Pharma, MedImmune, Merck, Novartis, Pfizer, Regeneron, Reistone, Roche, Sanofi, Sun Pharma, Teva, UCB Pharma and Valeant; served on advisory boards for AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eli Lilly, Galderma, GSK, Janssen, LEO Pharma, Mayne Pharma, Merck, Novartis, Pfizer, Sanofi, Sun Pharma, UCB Pharma and Valeant; served as a consultant for Aslan, Bristol Myers Squibb, Eli Lilly, Galderma, GenesisCare, Janssen, LEO Pharma, Mayne Pharma, MedImmune, Novartis, Pfizer, Roche, UCB Pharma and Wintermute; received travel grants from AbbVie, Eli Lilly, Galderma, Janssen, LEO Pharma, Merck, Novartis, Pfizer, Roche, Sun Pharma and Sanofi; served as a speaker for or received honoraria from AbbVie, Amgen, Celgene, Eli Lilly, Galderma, GSK, Janssen, LEO Pharma, Merck, Novartis, Pfizer, Roche, Sanofi, Sun Pharma and Valeant. R.G.L.: Principal Investigator for AbbVie, Amgen, Boehringer Ingelheim, Celgene, Eli Lilly, LEO Pharma, Merck, Novartis, Pfizer and UCB Pharma; served on scientific advisory boards for AbbVie, Amgen, Boehringer Ingelheim, Celgene, Eli Lilly, LEO Pharma, Merck, Novartis, Pfizer and UCB Pharma; provided lectures for AbbVie, Amgen, Celgene, Eli Lilly, LEO Pharma, Merck, Novartis and Pfizer. R.B.W.: Consulting fees from AbbVie, Almirall, Amgen, Arena, Astellas, Avillion, Biogen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eli Lilly, GSK, Janssen, LEO Pharma, Novartis, Pfizer, Sanofi and UCB Pharma; research grants to his institution from AbbVie, Almirall, Janssen, LEO Pharma, Novartis and UCB Pharma; honoraria from Astellas, DiCE, GSK and Union. M.W., V.V., B. Szilagyi.: Employees and shareholders of UCB Pharma. V.C.: Employee of UCB Pharma. C.P.: Consulting fees and/or grants from AbbVie, Almirall, Amgen, Boehringer Ingelheim, Celgene, Eli Lilly, GSK, Janssen Cilag, LEO Pharma, Novartis, Pfizer, Pierre Fabre, Sanofi and UCB Pharma., (© The Author(s) 2023. Published by Oxford University Press on behalf of British Association of Dermatologists.)

Introduction: Bimekizumab treatment resulted in improved clinical outcomes in patients with moderate-to-severe plaque psoriasis in BE VIVID, a 52-week, phase 3, randomized, ustekinumab and placebo-controlled study. We present data from the BE VIVID Japan patient subpopulation., Methods: Globally, patients were randomized to receive bimekizumab 320 mg every 4 weeks (Q4W), ustekinumab (45/90 mg weight-based at baseline and week 4, then every 12 weeks), or placebo (Q4W through week 16, then bimekizumab 320 mg Q4W). Efficacy endpoints included week 16 Psoriasis Area and Severity Index (PASI) 90 and Investigator's Global Assessment (IGA) 0/1, and other outcomes [PASI 100, PASI 75, IGA 0, Dermatology Life Quality Index (DLQI) 0/1, absolute PASI, scalp IGA, Psoriasis Symptoms and Impacts Measure (P-SIM) responses]. Safety analyses were conducted., Results: There were 108 Japanese randomized patients (bimekizumab: 62; ustekinumab: 29; placebo: 17). At week 16, bimekizumab-treated patients had a higher clinical response versus ustekinumab and placebo (PASI 90: 85.5% versus 51.7% and 5.9%; IGA 0/1: 82.3% versus 48.3% and 0.0%). Over 52 weeks, improved clinical response was maintained with bimekizumab, including patients switching from placebo at week 16. Overall, the safety profile in Japanese patients was consistent with that observed in the global population., Conclusion: Bimekizumab resulted in improved clinical response versus ustekinumab and placebo, and was well-tolerated in Japanese patients., Trial Registration: NCT03370133., (© 2023. The Author(s).)

Background: In the long-term extension study of the ERASURE and FIXTURE trials, the efficacy of secukinumab (a fully human anti-interleukin-17A monoclonal antibody) was demonstrated to have been maintained through to year 3 of treatment in moderate-to-severe plaque psoriasis., Objectives: To assess the efficacy and safety of secukinumab through to year 5 of treatment in moderate-to-severe plaque psoriasis., Methods: Responders with ≥ 75% improvement in Psoriasis Area and Severity Index (PASI 75) from two core trials - ERASURE and FIXTURE - were randomized 2 : 1 at year 1 (end of core trials) to either the same dose (300 or 150 mg, continuous treatment) or placebo (treatment withdrawal) every 4 weeks, until year 3 or relapse (> 50% reduction in maximal PASI from core study baseline). Partial responders (achieving PASI 50 but not PASI 75) at year 1 continued at the same dose as in the core trials. At year 3, all patients received open-label secukinumab treatment, with those on secukinumab 300 mg continuing on their dose, while those on secukinumab 150 mg or placebo received secukinumab 150 or 300 mg based on the physician's discretion. The study is registered on ClinicalTrials.gov with the identifier NCT01544595., Results: Most patients randomized to placebo at year 1 relapsed, but the response was rapidly recaptured upon reinitiation of treatment. PASI responses were sustained with secukinumab through to year 5. The PASI responses for the 300 mg responders + partial responders group at year 1 (PASI 75/90/100: 86.8%/72.8%/45.9%) trended downwards until year 3 (PASI 75/90/100: 82.3%/58.4%/32.7%) and then remained stable through year 4 (PASI 75/90/100: 83.3%/60.1%/32.2%) until year 5 (PASI 75/90/100: 81.1%/62.8%/35.1%). Dermatology Life Quality Index showed sustained benefit up to year 5. Absolute PASI responses were maintained throughout the study. The most common adverse events (AEs) were infections and infestations, nasopharyngitis, and upper respiratory tract infections (URTIs). The overall exposure-adjusted incidence rate (EAIR; with 95% confidence interval) for all AEs was 139.9 (130.3-149.9). EAIRs for Crohn's disease and neutropenia were 0.1 (0.0-0.3) and 0.5 (0.3-0.8), respectively., Conclusions: The 4-year extension of two pivotal phase III trials demonstrated that secukinumab treatment was effective through to year 5 and improved quality of life in patients with moderate-to-severe plaque psoriasis. The most common AEs were infections and infestations, nasopharyngitis, and URTIs. The safety profile was consistent with that in the secukinumab phase II/III clinical development programme., Competing Interests: Conflicts of interest: R.G.L. has served and received compensation in the form of grants and/or honoraria as principal investigator for, is on the scientific advisory board of, or has served as a speaker for AbbVie, Amgen, Boehringer Ingelheim, Celgene, Eli Lilly, Janssen, LEO Pharma, Merck, Novartis, Pfizer and UCB. H.S. is a clinical investigator for Boehringer Ingelheim, Novartis, Pfizer, Janssen, Lilly, Amgen and Merck; and is a consultant and member of the speakers’ bureau for Novartis, Janssen and Lilly. I.D.-C. has received compensation as a speaker, consultant and investigator for Novartis, Eli Lilly and Janssen. K.R. has served as an advisor and/or paid speaker for and/or has participated in clinical trials sponsored by AbbVie, Affibody, Amgen, Biogen, Boehringer Ingelheim Pharma, Celgene, Centocor, Covagen, Forward Pharma, GlaxoSmithKline, Janssen-Cilag, Kyowa Kirin, LEO Pharma, Lilly, Medac, Merck Sharp & Dohme Corp., Novartis, Ocean Pharma, Pfizer, Regeneron, Sanofi, Takeda, UCB Pharma and Xenoport. B.S. has consulted for Novartis and several other pharmaceutical companies; he has served on an advisory board for Novartis and several other pharmaceutical companies. R.B.W. has received research grants from AbbVie, Almirall, Amgen, Celgene, Janssen, Lilly, LEO Pharma, Novartis, Pfizer and UCB; and consulting fees from AbbVie, Almirall, Amgen, Boehringer Ingelheim, Celgene, Janssen, LEO, Lilly, Novartis, Pfizer, Sanofi, UCB and Xenoport. He is funded by a National Institute for Health Research (NIHR) Clinician Scientist award. He is supported by the NIHR Oxford Biomedical Research Centre. The views expressed are those of the authors and not necessarily those of the National Health Service, the NIHR or the Department of Health. C. Paul has been an investigator and consultant for AbbVie, Amgen, Boehringer Ingelheim, Celgene, GSK, Janssen, LEO Pharma, Lilly, Novartis and Pfizer. J.C.S. has served on an advisory board for LEO Pharma, Novartis, Sanofi Genzyme, Trevi and Viofor; has been a speaker for AbbVie, LEO Pharma, Novartis, Sanofi Genzyme and Sunfarm; and has served as an investigator for AbbVie, BMS, Galapagos, Galderma, Helm, Incyte, InflaRx, Janssen-Cilag, Novartis, Pfizer, Regeneron, Trevi and UCB. T.-F.T. has served as an investigator and/or speaker and/or advisor for AbbVie, Allergan, BMS, Boehringer Ingelheim, Celgene, Eli Lilly, Galderma, GSK, Janssen, LEO Pharma, MSD, Novartis, Pfizer, Sanofi Aventis and Tanabe. I.H., R.Y., P.C. and C. Papavassilis are employees of Novartis., (© The Author(s) 2022. Published by Oxford University Press on behalf of British Association of Dermatologists.)

Background: Psoriasis is a chronic immune-mediated inflammatory skin disease that often leads to a diminished quality of life. Goals of treating patients with psoriasis have shifted with more focus on achieving near or complete clearance of the skin. Guselkumab, a fully human monoclonal antibody targeting interleukin-23, is effective in treating moderate-to-severe psoriasis., Objective: To describe the baseline characteristics of patients with moderate-to-severe psoriasis achieving super-response (Psoriasis Area and Severity Index [PASI] 100 response at Weeks 20 and 28) after commencing guselkumab treatment., Methods: Pooled data from VOYAGE 1 and VOYAGE 2 studies identified super-response; baseline demographic, disease and pharmacokinetic characteristics were compared with non-super-response. A stepwise logistic regression analysis identified which factors were potentially predictive of super-response status, with significance level of 0.1., Results: A subset of patients randomized to guselkumab comprised this post hoc analysis (n = 664); 271 patients achieved super-response vs. 393 with non-super-response. Patient age at study entry and baseline body weight (≤90 kg vs. >90 kg), PASI, and Investigator's Global Assessment (IGA) score were significant predictors of super-response status, with odds ratios (95% confidence intervals) of 0.98 (0.967-0.993; P = 0.003), 1.42 (1.026-1.977; P = 0.034), 0.97 (0.955-0.993; P = 0.007) and 0.66 (0.433-0.997; P = 0.048), respectively. More patients with super-response achieved an early response: Week 2 PASI 75 (5.5% vs. 1.8%) and Week 8 PASI 100 (22.5% vs. 3.3%) vs. non-super-response. Median serum guselkumab concentrations through Week 28 were slightly greater in patients with super-response vs. non-super-response., Conclusion: Guselkumab was more likely to achieve early clinical responses (complete skin clearance) in younger patients, less obese patients and patients with less severe psoriasis., (© 2022 European Academy of Dermatology and Venereology.)

Introduction: In pivotal phase 3 tralokinumab monotherapy (ECZTRA 1/2) and topical corticosteroid (TCS) combination (ECZTRA 3) trials in adults with moderate-to-severe atopic dermatitis (AD), tralokinumab significantly improved signs and symptoms of AD. Geographic region may impact treatment response due to potential differences in race and ethnicity, and based on findings in other therapy areas. Here, we evaluated the efficacy and safety of tralokinumab in the ECZTRA 1/2/3 North American population at week 16, as well as maintenance of responses over time, and compared these data side-by-side with those of the ECZTRA 1/2/3 non-North American population., Methods: Primary endpoints were Investigator's Global Assessment score of 0 or 1 (IGA 0/1; clear or almost clear) or at least 75% improvement in Eczema Area and Severity Index (EASI-75) at week 16. At week 16, tralokinumab-treated IGA 0/1 or EASI-75 responders were re-randomized 2:2:1 to tralokinumab 300 mg q2w, or q4w, or placebo (ECZTRA 1/2) and 1:1 to tralokinumab 300 mg q2w or q4w (ECZTRA 3)., Results: Overall, 559/1596 (35%) and 160/380 (42.1%) patients randomized in ECZTRA 1/2 and ECZTRA 3 were from North America, respectively. At week 16, IGA 0/1 and EASI-75 response rates were greater with tralokinumab versus placebo in ECZTRA 1/2 (IGA 0/1: 25.3% vs 15.1%; 95% confidence interval [CI] 3.0, 17.3; p = 0.012; EASI-75, 40.1% vs 19.4%; 95% CI 12.6, 28.7; p < 0.001) and ECZTRA 3 (IGA 0/1, 40.0% vs 25.9%; 95% CI - 0.5, 28.3; p = 0.074; EASI-75: 58.1% vs 37.0%; 95% CI 4.9, 37.0; p = 0.012) and tralokinumab was well tolerated in the North American population. Patients with IGA 0/1 or EASI-75 response at week 16 demonstrated sustained responses at week 52 and week 32 in ECZTRA 1/2 and ECZTRA 3, respectively. Similar findings were observed in the non-North American trial populations., Conclusions: Tralokinumab, with or without TCS, displayed similar efficacy and safety in patients with moderate-to-severe AD across the North American population, and was comparable to the non-North American population., Clinical Trial Registration: NCT03131648 (registered 27-Apr-2017); NCT03160885 (registered 19-May-2017); NCT03363854 (registered 6-Dec-2017)., (© 2022. The Author(s).)

Background: Additional long-term treatments are needed for moderate-to-severe atopic dermatitis (AD). An ongoing, open-label, 5-year extension trial, ECZTEND (NCT03587805), assesses tralokinumab plus optional topical corticosteroids in participants from previous tralokinumab parent trials (PTs) with moderate-to-severe AD., Objective: To evaluate the safety and efficacy of up to 2 years tralokinumab treatment in a post hoc interim analysis., Methods: Safety analyses included adults from completed PTs enrolled in ECZTEND, regardless of tralokinumab exposure duration. Efficacy analyses included adult participants treated with tralokinumab in ECZTEND for ≥1 year and subgroup analyses of those on tralokinumab for 2 years (1 year from PT, 1 year in ECZTEND). Primary end point was the number of adverse events with additional efficacy end points., Results: Participants on tralokinumab had an exposure-adjusted rate of 237.8 adverse events/100 patient-years' exposure (N = 1174) in the safety analysis set. Exposure-adjusted incidence rates of common adverse events were comparable to PTs, although at lower rates. With 2 years of tralokinumab, improvements in extent and severity of AD were sustained, with Eczema Area and Severity Index (EASI-75) in 82.5% of participants (N = 345)., Limitations: Possible selection bias; no placebo arm; some participants experienced treatment gaps between PTs and ECZTEND., Conclusion: Over 2 years, tralokinumab was well tolerated and maintained long-term control of AD signs and symptoms., Competing Interests: Conflicts of interest Blauvelt has served as a scientific adviser and/or clinical study investigator for AbbVie, Abcentra, Aligos, Almirall, Amgen, Arcutis, Arena, Aslan, Athenex, Boehringer Ingelheim, Bristol-Myers Squibb, Dermavant, EcoR1, Eli Lilly, Evommune, Forte, Galderma, Incyte, Janssen, Landos, LEO Pharma, Novartis, Pfizer, Rapt, Regeneron, Sanofi Genzyme, Sun Pharma, UCB Pharma, and Vibliome. Langley has served and received compensation in the form of grants and/or honoraria as principal investigator for and is on the scientific advisory board or has served as a speaker for AbbVie, Amgen, Boehringer Ingelheim, Celgene, Eli Lilly, Janssen, LEO Pharma, Merck, Novartis, Pfizer, and UCB. Lacour has received grants or honoraria as an investigator, advisory board member, or speaker from AbbVie, Amgen, Boehringer Ingelheim, Celgene, Dermira, Janssen, Lilly, LEO Pharma, Novartis, Pfizer, Regeneron, and Sanofi. Toth has served as an investigator for AbbVie, Amgen, Arcutis, Boehringer Ingelheim, Bond Avillion, Bristol-Myers Squibb, Celgene, Centocor, Dermira, Eli Lilly, Galderma, GSK, Incyte, Janssen, LEO Pharma, Merck, Novartis, Pfizer, Regeneron, UCB, and Valeant. Laquer has received grants from AbbVie, Eli Lilly, Galderma, LEO Pharma, and Novartis. Beissert has served an advisory board member or received speaker honoraria from AbbVie Deutschland & Co, Actelion Pharmaceuticals, Almirall-Hermal, Amgen, BMS, Celgene, Galderma, GSK, Hexal-Sandoz, Janssen-Cilag, LEO Pharma, Lilly Deutschland, Menlo Therapeutics, MSD Sharp & Dohme, Novartis, Pfizer, Roche-Posay, Sanofi-Aventis Deutschland, and UCB Pharma. Wollenberg has received grants, personal fees, or nonfinancial support from AbbVie, Almirall, Beiersdorf, Bioderma, Chugai, Galapagos, Galderma, Hans Karrer, LEO Pharma, Lilly, L'Oreal, Maruho, MedImmune, Novartis, Pfizer, Pierre Fabre, Regeneron, Santen, and Sanofi-Aventis. Herranz has served as a consultant, speaker, or investigator for Amgen, Janssen, LEO Pharma, Lilly, Novartis, Parexel, Pfizer, and Sanofi. Pink reports personal fees and nonfinancial support from LEO Pharma, Novartis, and UCB and personal fees from AbbVie, Almirall, Amgen, BMS, Boehringer, Janssen, La Roche-Posay, Lilly, Pfizer, and Sanofi. Peris reports grants or personal fees for participation in advisory boards from AbbVie, Almirall, Galderma, Lilly, LEO Pharma, Novartis, Pierre Fabre, Sanofi, Sun Pharma, and Janssen. Fangel, Gjerum, and Corriveau are employees of LEO Pharma. Saeki has received lecture fees from Kyorin, Kyowa Kirin, LEO Pharma, Mitsubishi Tanabe, Maruho, Sanofi, Tokiwa, and Taiho and scholarship donations from Esai, Mitsubishi Tanabe, Maruho, and Torii. Warren has received research grants or consulting fees from AbbVie, Almirall, Amgen, Arena, Astellas, Avillion, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, DiCE, Eli Lilly, GSK, Janssen, LEO Pharma, Medac, Novartis, Pfizer, Sanofi, Sun Pharma, UCB, and UNION. He is supported by the Manchester NIHR Biomedical Research Centre. Simpson reports grants and/or personal fees from AbbVie, Boehringer Ingelheim, Celgene, Dermavant, Dermira, Eli Lilly, FortéBio, Galderma, Incyte, Kyowa Kirin, LEO Pharma, MedImmune, Menlo Therapeutics, Merck, Novartis, Ortho Dermatologics, Pfizer, Pierre Fabre Dermo Cosmetique, Regeneron, Sanofi, Tioga, and Valeant. Reich has served as advisor and/or paid speaker for and/or participated in clinical trials sponsored by Abbvie, Almirall, Amgen, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Forward Pharma, Gilead, Galderma, Janssen-Cilag, Kyowa Kirin, LEO, Lilly, Medac, Novartis, Ocean Pharma, Pfizer, Sanofi, and UCB. Professor Reich is cofounder of Moonlake Immunotherapeutics., (Copyright © 2022 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

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.

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.

Background: Guselkumab effectively treats moderate-to-severe psoriasis., Objective: To evaluate the cumulative safety experience of guselkumab using pooled data from the VOYAGE 1 and 2 studies through 5 years., Methods: Patients were randomized to guselkumab, placebo with crossover to guselkumab at week 16, or adalimumab. The studies were identical through week 24. VOYAGE 1 evaluated continuous guselkumab treatment (adalimumab-crossover-to-guselkumab at week 52), while VOYAGE 2 assessed randomized withdrawal/retreatment (weeks 28-76). Open-label guselkumab treatment was administered starting at week 52 in VOYAGE 1 and week 76 in VOYAGE 2 and continued through week 252. Pooled safety data were adjusted by exposure and analyzed in the guselkumab groups, including placebo-crossover-to-guselkumab (n = 1221) and adalimumab-crossover-to-guselkumab (n = 500), through week 264., Results: Patients were followed for a total of 7166 patient-years (PY). Overall, 1349 of 1721 guselkumab-treated patients (78.4%) continued treatment through week 252. The rates of adverse and serious adverse events were 149/100 PY and 5.01/100 PY, respectively. Rates of adverse events of interest were low: serious infections (0.85/100 PY), nonmelanoma skin cancer (0.34/100 PY), malignancies other than nonmelanoma skin cancer (0.45/100 PY), and major adverse cardiovascular events (0.29/100 PY). Year-to-year variability was evident, but no increasing trend was observed., Limitations: No direct treatment comparisons were possible after week 52., Conclusion: The safety profile remained consistent and favorable during 5 years of continuous guselkumab treatment of psoriasis., Competing Interests: Conflicts of interest Dr Blauvelt has served as a scientific advisor and/or clinical study investigator for AbbVie, Abcentra, Aligos, Almirall, Amgen, Arcutis, Arena, Aslan, Athenex, Boehringer Ingelheim, Bristol Myers Squibb, Dermavant, Eli Lilly and Company, Evommune, Forte, Galderma, Incyte, Janssen, Landos, LEO Pharma, Novartis, Pfizer, Rapt, Regeneron, Sanofi Genzyme, Sun Pharmaceutical, and UCB Pharma. Dr Tsai has served as a consultant for AbbVie, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Galderma, GlaxoSmithKline, Janssen, LEO Pharma, Lilly, Merck Sharpe & Dohme, Novartis, Pfizer, and UCB. Dr Langley has received honoraria as principal investigator, scientific advisory board member, and/or lecturer for AbbVie, Amgen, Boehringer Ingelheim, Celgene, Eli Lilly, Janssen, LEO Pharma, Merck, Novartis, Pfizer, Sun Pharmaceutical, and UCB Pharma. Drs Miller, Shen, and You are employees of Janssen Research & Development, LLC. Dr Yang is an employee of Immunology Global Medical Affairs, Janssen Pharmaceutical Companies of Johnson & Johnson (employees may own stock in Johnson & Johnson, of which Janssen is a subsidiary). Dr Papp has served as a consultant, scientific advisor, investigator, consultant, speaker, and/or medical officer for AbbVie, Akros, Amgen, Anacor, Arcutis, Astellas, Avillion, Bausch Health, Baxalta, Boehringer Ingelheim, Bristol Myers Squibb, Can-Fite Biopharma, Celgene, Coherus, Dermavant, Dermira, Dow Pharma, Eli Lilly, Evelo, Galapagos, Galderma, Genentech, Gilead, GlaxoSmithKline, Incyte, Janssen, Kyowa Hakko Kirin, LEO Pharma, Medimmune, Meiji Seika Pharma, Merck Sharpe & Dohme, Merck-Serono, Mitsubishi Pharma, Moberg Pharma, Novartis, Pfizer, PRCL Research, Regeneron, Roche, Sanofi-Aventis/Genzyme, Sun Pharma, Takeda, UCB Pharma, and Valeant. Dr Puig has received consultancy/speaker's honoraria from and/or participated in clinical trials sponsored by AbbVie, Almirall, Amgen, Baxalta, Biogen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Fresenius-Kabi, Gebro, Janssen, JS BIOCAD, LEO Pharma, Lilly, Merck-Serono, MSD, Mylan, Novartis, Pfizer, Regeneron, Roche, Sandoz, Samsung-Bioepis, Sanofi, and UCB., (Copyright © 2021 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Risankizumab has demonstrated efficacy and safety in patients with moderate-to-severe plaque psoriasis in randomized clinical trials., Objectives: To evaluate safety data from risankizumab psoriasis phase I-III clinical trials., Methods: Short-term safety (through week 16) was analysed using integrated data from five phase II and III clinical trials. Long-term safety was evaluated using integrated data from 17 phase I-III completed and ongoing trials., Results: Short-term safety analyses included 1306 patients receiving risankizumab 150 mg and 300 patients receiving placebo [402·2 and 92·0 patient-years (PY) of exposure, respectively]. Long-term analyses included 3072 risankizumab-treated patients (exposure: 7927 PY). The median (excluding four outliers) treatment duration was 2·9 years (range 2 days to 5·9 years). Exposure-adjusted adverse event rates did not increase with long-term treatment (318 vs. 171 events per 100 PY for short- and long-term analyses). With long-term risankizumab treatment, rates of serious adverse events were 7·8 per 100 PY, serious infections 1·2 per 100 PY, nonmelanoma skin cancer (NMSC) 0·7 per 100 PY, malignant tumours excluding NMSC 0·5 per 100 PY, and adjudicated major adverse cardiovascular events 0·3 per 100 PY, with no important identified risks. Limitations include that the study inclusion and exclusion criteria varied and that three studies enrolled ≤ 50 patients., Conclusions: Risankizumab demonstrated a favourable safety profile over short- and long-term treatment in patients with moderate-to-severe psoriasis., (© 2021 The Authors. British Journal of Dermatology published by John Wiley & Sons Ltd on behalf of British Association of Dermatologists.)

Plaque psoriasis is an immune-mediated inflammatory skin disease associated with the dysregulation of cytokines, especially those involved in the interleukin (IL)-23/IL-17 pathways. In recent years, there has been growing interest in developing biologic therapies that target these pathways. However, inhibition of the cytokines of the IL-23/IL-17 pathways may increase patients' risk of developing fungal infections, particularly oral candidiasis. Therefore, it is important that dermatology practitioners can effectively diagnose and treat oral candidiasis. In this review, we examine the role of the IL-23/IL-17 pathways in antifungal host defense, and provide a practical guide to the diagnosis and treatment of oral candidiasis in patients with psoriasis. Overall, while treatment with anti-IL-17 medications leads to an increased incidence of oral candidiasis in patients with psoriasis, these cases are typically mild or moderate in severity and can be managed with standard antifungal therapy without discontinuing treatment for psoriasis. If applicable, patients with psoriasis should also be advised to practice good oral hygiene and manage or control co-existing diabetes, and should be provided with information on smoking cessation to prevent oral candidiasis., (© 2022. The Author(s).)

Introduction: Patients with moderate-to-severe plaque psoriasis who experience poor clinical outcomes, including patients with obesity or prior treatment, need improved treatment options. Risankizumab specifically inhibits interleukin 23 and has demonstrated superior efficacy in active-comparator studies in patients with moderate-to-severe plaque psoriasis. We compared the efficacy of risankizumab with that of secukinumab across patient subgroups., Methods: Subgroup analyses using data from the phase 3 IMMerge study (NCT03478787) were performed. Efficacy in adults with moderate-to-severe psoriasis treated with risankizumab 150 mg and secukinumab 300 mg was assessed as the proportion of patients who achieved ≥ 90% improvement in Psoriasis Area Severity Index (PASI 90) at week 52 across demographics and disease characteristics. Post hoc analyses evaluated the proportion of patients who achieved PASI 90 and the least-squares mean percent PASI improvement from baseline at week 52 by body weight and body mass index (BMI), PASI 90 by prior treatment, and clinical response [PASI 90, PASI 100, and/or static Physician's Global Assessment (sPGA) score of clear (0) or almost clear (1)] at week 16 and maintained particular response at week 52. Logistic regression analyses examined the effect of covariates (age, sex, BMI, baseline PASI, treatment) and potential interactions on PASI 90 at week 52., Results: More patients who received risankizumab (n = 164) compared with secukinumab (n = 163) achieved PASI 90 at week 52, regardless of demographics and disease characteristics (BMI, prior treatment, disease duration, and maintenance of clinical response at week 52). Improvements in PASI were greater in patients taking risankizumab than those taking secukinumab, regardless of weight or BMI. Results from logistic regression analysis showed treatment type had a significant impact on PASI 90 (risankizumab versus secukinumab, p < 0.0001)., Conclusion: Risankizumab showed consistently greater efficacy compared with secukinumab across different patient subgroups, and this was maintained through 52 weeks., Trial Registration: ClinicalTrials.gov identifier; NCT03478787., (© 2022. The Author(s).)

Introduction: Since the 2012 Multinational Assessment of Psoriasis and Psoriatic Arthritis (MAPP) survey, several systemic treatments for psoriasis (PsO) and/or psoriatic arthritis (PsA) have been approved. The population-based UPLIFT survey was conducted to understand how perceptions of treatment-related outcomes have evolved, particularly for patients with mild to moderate PsO and/or PsA and their dermatologists., Methods: This population- and web-based survey was conducted from 2 March to 3 June 2020, in North America, Europe, and Japan. Adults with self-reported healthcare practitioner (HCP)-diagnosed PsO and/or PsA and dermatologists who spent > 50% of time treating patients and treated ≥ 20 patients with PsO, including plaque PsO, per month were included. Patient participants were recruited at random from online panels; dermatologists were recruited randomly from representative physician panels., Results: Of 264,054 patient responses, 3806 who self-reported an HCP diagnosis of PsO and/or PsA were included in the final sample; 67% had PsO alone, 28% had PsO and PsA, and 5% had PsA alone. The estimated population prevalence of psoriatic disease was 7% (PsO only: 4%; PsO and PsA: 2%; PsA only: 1%). Most patients (78%) reported PsO-involved body surface area (BSA) ≤ 3 palms, and ~ 90% or more reported itching, redness, flaking, and scales. Many PsO patients without diagnosed PsA reported musculoskeletal symptoms suggestive of PsA (63%). Across BSA categories, approximately one in four patients was not currently receiving treatment and > 50% had Dermatology Life Quality Index score > 5. Patients and dermatologists had different perceptions of PsO severity, office visit discussions, treatment goals, and treatment satisfaction. The survey was conducted during the coronavirus disease 2019 (COVID-19) pandemic, which could have affected assessments of patient-reported outcomes and ability to have in-person HCP visits., Conclusions: Patients with PsO and PsA in UPLIFT reported high disease burden, including patients with limited skin involvement. An opportunity exists to align patient and dermatologist perceptions to optimize management of PsO and PsA., Infographic: DIGITAL FEATURE: This article is published with digital features, including an infographic, to facilitate understanding of the article. To view digital features for this article go to https://doi.org/10.6084/m9.figshare.17104586 ., (© 2021. The Author(s).)

Background: Anti-interleukin (IL)-17 biologic agents used to treat psoriasis are associated with onset/exacerbation of inflammatory bowel disease (IBD)., Objectives: To determine the incidence of IBD or serious gastrointestinal-related adverse events (GI SAEs) in patients with moderate-to-severe psoriasis treated with guselkumab, an IL-23p19 inhibitor that indirectly inhibits IL-17, through 4 years in the phase 3 VOYAGE 1 and VOYAGE 2 trials., Methods: Patients were randomized to guselkumab 100 mg every-8-weeks or placebo&rarr;guselkumab (week 16), or adalimumab. In VOYAGE 1, all patients received open-label guselkumab starting at week 52. In VOYAGE 2, eligible patients were treated with guselkumab or placebo based on clinical response starting at week 28 and received open-label guselkumab starting at week 76. Cumulative incidence rates of IBD and other GI SAEs were calculated as events per 100 patient-years (PY) through week 204. IBD was defined as AEs of Crohn&rsquo;s disease or ulcerative colitis. Data were summarized for all guselkumab-treated patients for years 1-4., Results: Of 1721 guselkumab-treated patients, 1612 were exposed for &ge;1 year, 1545 for &ge;2 years, 1454 for &ge;3 years, and 661 for &ge;4 years. For all patients through week 204, the cumulative rate of GI SAEs was 0.45/100PY. Event rates remained stable with longer duration of exposure, ranging from 0.36 to 0.57/100PY. No new or exacerbated cases of IBD were reported., Conclusions: No cases of IBD were observed and rates of GI SAEs were low through 4 years of treatment with guselkumab in two large trials of patients with psoriasis. J Drugs Dermatol. 2021;20(8):855-860. doi:10.36849/JDD.6216 THIS ARTICLE HAD BEEN MADE AVAILABLE FREE OF CHARGE. PLEASE SCROLL DOWN TO ACCESS THE FULL TEXT OF THIS ARTICLE WITHOUT LOGGING IN. NO PURCHASE NECESSARY. PLEASE CONTACT THE PUBLISHER WITH ANY QUESTIONS.