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Background: Janus kinase (JAK) inhibition is a new mode of action in atopic dermatitis (AD); clarity about drug class safety considerations in the context of AD is important. Baricitinib, an oral, reversible, selective inhibitor of JAK1/JAK2, is in late‐stage development for adult patients with moderate‐to‐severe AD. Objective: To report pooled safety data for baricitinib in patients with moderate‐to‐severe AD in the clinical development program including long‐term extension (LTE) studies. Methods: This analysis included patient‐level safety data from six double‐blinded, randomized, placebo‐controlled studies (one phase 2 and five phase 3), one double‐blinded, randomized, LTE study and one open‐label LTE study, reported in three data sets: placebo‐controlled, 2‐mg – 4‐mg extended and All‐bari AD. Safety outcomes include treatment‐emergent adverse events, adverse events of special interest and abnormal laboratory changes. Proportions of patients with events and incidence rates were calculated. Results: Data were collected for 2531 patients who were given baricitinib for 2247 patient‐years (median duration 310 days). The frequency of serious infections, opportunistic infections and conjunctival disorders was low and similar between treatment groups in the placebo‐controlled period. The most common serious infections were eczema herpeticum [n = 11, incidence rates (IR) = 0.5], cellulitis (n = 6, IR = 0.3) and pneumonia (n = 3, IR = 0.1). There were four opportunistic infections (IR = 0.2). No malignancies, gastrointestinal perforations, positively adjudicated cardiovascular events or tuberculosis were reported in the placebo‐controlled period in baricitinib‐treated patients. Frequency of herpes simplex was higher in the 4‐mg group (6.1%) vs. the 2‐mg (3.6%) and placebo group (2.7%); IRs in the extended data set (2‐mg IR = 9.6; 4‐mg IR = 14.5) were lower vs. the placebo‐controlled data set (2‐mg IR = 12.4; 4‐mg IR = 21.3). In the All‐bari AD data set, there were two positively adjudicated major adverse cardiovascular events (2‐mg group): two venous thrombosis events (4‐mg group) and one death. Conclusion: This integrated safety analysis in patients with moderate‐to‐severe AD confirms the established safety profile of baricitinib. [ABSTRACT FROM AUTHOR]

Generalized pustular psoriasis (GPP) is a severe rare skin disease characterized by widespread eruption of sterile superficial macroscopic pustules with or without systemic inflammation. Generalized pustular psoriasis flares may lead to life-threatening multiorgan complications, which highlights the need for rapid and accurate diagnosis. However, the rarity of the disease and its heterogeneous cutaneous and extracutaneous symptoms, and the resemblance of symptoms to other skin conditions, pose considerable challenges to the timely diagnosis and treatment of patients with GPP. Current laboratory tests used for GPP diagnosis are generally not GPP specific, and are mainly focused on the assessment of inflammatory markers and clinical and histopathologic features of GPP, and emerging genetic screening approaches. A differential diagnosis to distinguish GPP from other similar conditions requires careful assessment of the patient's skin symptoms, potential disease triggers, medical history, histopathologic features, laboratory tests, and clinical disease course. The comprehensive interpretation of these assessments can be challenging owing to the lack of standardized global guidelines. While there is currently a lack of standardized international guidelines for the diagnosis of GPP, recent advances in our understanding of the genetics and pathogenesis of the disease have provided new opportunities to enhance diagnosis. In the future, defining specific GPP subtypes using genetic and histopathologic strategies will guide therapeutic decisions, allowing patients to achieve their treatment goals without delay. In this article, we provide an overview of the current diagnostic methods, differential diagnostic strategies, and future advances in the diagnosis of GPP, as well as features of GPP variants., (© 2022. The Author(s).)

Background: Patients with mild-to-moderate psoriasis may have substantial quality-of-life impairment., Objective: To evaluate apremilast 30 mg twice daily for mild-to-moderate psoriasis., Methods: Phase 3, double-blind, placebo-controlled study in adults with mild-to-moderate psoriasis inadequately controlled or intolerant to ≥ 1 topical psoriasis therapy (NCT03721172). The primary endpoint was the achievement of static Physician Global Assessment score of 0 (clear) or 1 (almost clear) and ≥ 2-point reduction at week 16., Results: Five hundred ninety-five patients were randomized (apremilast: 297; placebo: 298). The primary endpoint was met, with a significantly greater static Physician Global Assessment response rate observed at week 16 in the apremilast group compared with the placebo group (21.6% vs 4.1%; P < .0001). All secondary endpoints were met with the achievement of body surface area-75 (33.0% vs 7.4%), body surface area ≤ 3% (61.0% vs 22.9%), ≥ 4-point reduction in Whole Body Itch Numeric Rating Scale (43.2% vs 18.6%), Scalp Physician Global Assessment 0 or 1 and ≥ 2-point reduction (44.0% vs 16.6 %), and changes from baseline in body surface area, Psoriasis Area and Severity Index, and Dermatology Life Quality Index (all P < .0001). The most commonly reported adverse events (≥ 5%) with apremilast were diarrhea, headache, nausea, nasopharyngitis, and upper respiratory tract infection, consistent with prior studies., Limitations: The study lacked an active-comparator arm., Conclusion: Apremilast demonstrated efficacy in mild-to-moderate psoriasis and safety consistent with the established safety profile of apremilast., Competing Interests: Conflicts of interest Dr Gold received honoraria, grants, and/or research funding as a speaker, investigator, and/or advisory board member for AbbVie, Amgen Inc, Arcutis, Celgene Corporation, Dermira, Dermavant, Eli Lilly, Galderma, LEO Pharma, Novartis, Pfizer, Regeneron, Sanofi Genzyme, UCB, and Valeant. Dr Papp was a steering committee member for PSLOAR and PURE and received honoraria, grants, and/or research funding as a speaker, investigator, advisory board member, data safety monitoring board member, and/or consultant for AbbVie, Actelion, Amgen Inc, Astellas Pharma US, Boehringer Ingelheim, Bausch Health, Celgene Corporation, Dermira, Dow Pharmaceuticals, Eli Lilly, Frontier, Galderma, Janssen, Kyowa Hakko Kirin Pharma, LEO Pharma, MedImmune, Merck & Co, Inc, Novartis, Pfizer, Regeneron, Roche Laboratories, Sanofi Genzyme, Takeda Pharmaceuticals, UCB, and Valeant. Dr Pariser received honoraria or was an investigator, advisory board member, or data monitoring board member for Amgen Inc, AO Biome, Asana, Brickel Biotech, Celgene Corporation, Dermavant, Dermira, Eli Lilly, Menlo Therapeutics, Merck, Novartis, Ortho, Regeneron, Atacama, Biofrontera, Bristol Myers Squibb, LEO Pharma, Pfizer, Sanofi, and Valeant. Dr Green was an investigator, speaker, and/or consultant for AbbVie, Amgen Inc, Arcutis, Dermavant, MC2, Novartis, Lilly, OrthoDerm, SunPharma, and UCB. Dr Bhatia was an advisor, consultant, investigator, and/or speaker for AbbVie, Actavis, Allergan, Amgen Inc, Aqua, Bayer, Biofrontera, BiopharmX, Castle, Cipher, Dermira, Encore, Exeltis, Ferndale, Foamix, Galderma, Intraderm, ISDIN, LaRoche-Posay, LEO Pharma, Novan, Novartis, PharmaDerm, Pfizer, Promius, Regeneron, Sanofi, Sun Pharma, and Valeant. Dr Sofen received honoraria, grants, and/or research funding as an investigator and/or advisory board member for AbbVie, Amgen Inc, Celgene Corporation, Dermira, Dermavant, Eli Lilly, Galderma, LEO Pharma, Novartis, Pfizer, and UCB. Dr Albrecht received honoraria, grants, and/or research funding as a speaker, investigator, advisory board member, and/or consultant for AbbVie, Amgen Inc, Arcutis, Boehringer Ingelheim, Bausch Health/Valeant, Celgene Corporation, Dermira, Dermavant, Eli Lilly, Galderma, Janssen, LEO Pharma, MedImmune, Merck & Co, Novartis, Pfizer, Regeneron, Roche Laboratories, Sanofi Genzyme, and UCB. Dr Gooderham received honoraria, grants, and/or research funding as a speaker, investigator, advisory board member, data safety monitoring board member, and/or consultant for AbbVie, Amgen Inc, Akros, Arcutis, Bausch/Valeant, Boehringer Ingelheim, Celgene Corporation, Dermira, Dermavant, Eli Lilly, Galderma, Janssen, Kyowa Hakko Kirin Pharma, LEO Pharma, MedImmune, Merck & Co, Novartis, Pfizer, Regeneron, Roche Laboratories, Sanofi Genzyme, Takeda Pharmaceuticals USA Inc, and UCB. Author Chen and Dr Paris are employees of Amgen Inc. Dr Wang was employed by Amgen Inc at time of the study. Dr Callis Duffin received honoraria, grants, and/or research funding as an investigator, advisory board member, consultant, and/or non-promotional speaker for AbbVie, Amgen Inc, Boehringer Ingelheim, Celgene Corporation, Eli Lilly, Janssen, Novartis, Pfizer, Regeneron, and UCB., (Copyright © 2021 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Psoriasis (PsO) requires safe and effective long-term management to reduce the risk of recurrence and decrease the frequency of relapse. Topical PsO therapies are a cornerstone in the management of PsO though safety concerns limit the chronic, continuous use of topical corticosteroids and/or vitamin D 3 analogs. Evidence-based guidelines on optimal treatment targets and maintenance therapy regimens are currently lacking. This review explores the evidence supporting approaches to maintenance topical therapy for PsO including continuous long-term therapy, chronic intermittent use, step-down therapy, sequential or pulse therapy regimens, and proactive maintenance therapy. Several unaddressed questions are discussed including how and when to transition from acute to maintenance therapy, strategies for monitoring long-term treatment, the role of topical maintenance therapy in the context of systemic and biologic therapies, risks of maintenance therapy, prescribing a topical preparation suitable for patients' preferences and skin type, and key concepts for patient education to maximize long-term outcomes. Overall, emerging evidence supports a paradigm shift toward proactive treatment once skin is completely clear as a strategy to enhance disease control without compromising safety., (© 2021 The Authors. Dermatologic Therapy published by Wiley Periodicals LLC.)

Summary: Background: Chronic psoriasis may require medication adjustments over time. Objectives: To evaluate the efficacy/safety of tildrakizumab in subgroups from the reSURFACE studies (N = 1862) that received continuous dosing, higher/lower dosing, treatment interruption/reinitiation and initiation. Methods: Responders [Psoriasis Area and Severity Index (PASI) ≥ 75%] and partial responders (PASI ≥ 50% to < 75%) in Part 3 of the reSURFACE studies (weeks 28–52 or week 64) who received tildrakizumab 200 mg or 100 mg were rerandomized to the same dosage (T100/T100 or T200/T200), a higher/lower dosage (T100/T200 or T200/T100) or placebo (PBO) (T100/PBO or T200/PBO). Patients receiving PBO who relapsed were reinitiated to tildrakizumab. Etanercept (ETN) week‐28 partial responders and nonresponders (PASI < 50%) received tildrakizumab 200 mg (ETN/T200). Results: Among T100/T100 and T200/T200 week‐28 partial responders, the proportion of patients who achieved as‐observed PASI 75 responses increased over time. Among T100/T200 week‐28 partial responders, PASI 75 responses increased from week 32 (38·5%) to week 52 (63·2%) and remained consistent in T200/T100 week‐28 responders. Among patients who relapsed in the T100/PBO and T200/PBO groups, 86% and 83% of those who reinitiated tildrakizumab achieved PASI 75 by week 64, respectively. Among ETN/T200 week‐28 partial responders, PASI 75 responses (nonresponder imputation) increased from week 32 (24·1%) to week 52 (74·7%). PASI 90, PASI 100 and Physician's Global Assessment responses were consistent with PASI 75 results. Treatment was well tolerated. Conclusions: Patients generally fared well with tildrakizumab maintenance, reinitiation, dose adjustment or initiation. What's already known about this topic? Tildrakizumab demonstrated significant efficacy vs. placebo with a positive safety profile during the first 28 weeks of treatment in two randomized double‐blind trials. What does this study add? Treatment scenarios with tildrakizumab, such as long‐term continuous dosing (up to 64 weeks), treatment interruption/reinitiation and switching from another biologic, can be part of the management of plaque psoriasis with a reasonable expectation of efficacy and tolerability. Plain language summary available online Respond to this article [ABSTRACT FROM AUTHOR]

Background: Previous studies of dupilumab in adolescents and adults with moderate-to-severe atopic dermatitis (AD) showed no clinically meaningful adverse changes in laboratory parameters., Objective: The aim of this study was to assess laboratory outcomes in children aged 6-11 years with severe AD in a randomized, placebo-controlled, phase III trial of dupilumab., Methods: Children aged 6-11 years with severe AD were randomized 1:1:1 to 16 weeks of dupilumab 300 mg every 4 weeks, 100 or 200 mg every 2 weeks, or matching placebo, all with concomitant topical corticosteroids (TCS). Blood samples were collected at baseline and Weeks 4, 8, and 16; urine samples were collected at baseline and Weeks 4 and 16., Results: Of 367 patients enrolled in the study, 362 were included in the safety analysis, 351 completed study treatment, and 4 withdrew due to treatment-emergent adverse events not related to laboratory abnormalities. Both dupilumab + TCS groups showed overall trends toward increases in mean blood levels of eosinophils and alkaline phosphatase, and decreases in mean blood levels of platelets, neutrophils, and lactate dehydrogenase levels, without corresponding mean changes in the placebo + TCS group. None of these changes were associated with symptoms or clinically meaningful adverse outcomes, and none led to treatment modification. No clinically significant changes or trends were observed for other measured laboratory parameters., Conclusion: There were no clinically meaningful adverse changes in routine laboratory parameters attributable to treatment with dupilumab + TCS. Changes in platelet counts and lactate dehydrogenase levels likely reflect reduced inflammation. These results confirm similar findings in adults and adolescents, and suggest that there is no need for routine laboratory monitoring of children aged 6-11 years treated with dupilumab + TCS for severe AD., Trial Registration: ClinicalTrials.gov Identifier: NCT03345914. Does treatment with dupilumab require routine laboratory monitoring in 6- to 11-year-old children with severe atopic dermatitis? (MP4 180482 kb)., (© 2021. The Author(s).)

Introduction: Ixekizumab, a high-affinity monoclonal antibody that selectively targets interleukin-17A, is an approved treatment for plaque psoriasis. This study aimed to use animated visualizations as a tool to simplify complex data from ixekizumab clinical trials., Methods: Animated visualizations were developed to show outcomes from ixekizumab clinical trials and a Bayesian network meta-analysis of 11 approved biologics. The visualizations simultaneously highlighted both aggregate scores and the individual progression of patients over the course of treatment., Results: The animations provided key messages and information from the complex data in efficient and scientific ways that were also visually pleasing and simple to understand. The animations highlighted (1) rapid reduction in disease severity from baseline; (2) sustained efficacy of ixekizumab in the treatment of skin and nail psoriasis; (3) side-by-side comparisons of treatment efficacy and clinical improvement across trials; (4) simultaneous visual presentation of individual results with summary response over time; and (5) indirect comparison of relative treatment effects with other biologics based on Bayesian network meta-analysis., Conclusion: The rapid and sustained efficacy of ixekizumab in the treatment of psoriasis was demonstrated using multiple dynamic visualizations with different clinical endpoints. Animated visualizations provided a simpler and more comprehensive understanding of complex data than conventional static figures., (© 2021. The Author(s).)

Background: Bimekizumab is a monoclonal IgG1 antibody that selectively inhibits both interleukin-17A and interleukin-17F. The efficacy and safety of bimekizumab as compared with secukinumab, which selectively inhibits interleukin-17A alone, in patients with moderate-to-severe plaque psoriasis have not been extensively examined., Methods: In this phase 3b trial, we randomly assigned patients with moderate-to-severe plaque psoriasis, in a 1:1 ratio, to receive bimekizumab subcutaneously at a dose of 320 mg every 4 weeks or secukinumab subcutaneously at a dose of 300 mg weekly to week 4, followed by every 4 weeks to week 48. At week 16, patients receiving bimekizumab underwent rerandomization, in a 1:2 ratio, to receive maintenance dosing every 4 weeks or every 8 weeks to week 48. The primary end point was 100% reduction from baseline in the Psoriasis Area and Severity Index (PASI) score at week 16. The primary analysis was first tested for the noninferiority of bimekizumab to secukinumab at a margin of -10 percentage points and then tested for superiority., Results: A total of 1005 patients were screened and 743 were enrolled; 373 patients were assigned to receive bimekizumab and 370 to receive secukinumab. At week 16, a total of 230 patients (61.7%) in the bimekizumab group and 181 (48.9%) in the secukinumab group had a 100% reduction from baseline in the PASI score (PASI 100) (adjusted risk difference, 12.7 percentage points; 95% confidence interval [CI], 5.8 to 19.6); bimekizumab was shown to be noninferior and superior to secukinumab (P<0.001 for noninferiority and superiority). At week 48, a total of 250 patients (67.0%) treated with bimekizumab had a PASI 100 response, as compared with 171 patients (46.2%) treated with secukinumab (adjusted risk difference, 20.9 percentage points; 95% CI, 14.1 to 27.7; P<0.001). At the week 4 time point, 265 patients (71.0%) in the bimekizumab group had 75% or greater reduction from baseline in the PASI score, as compared with 175 patients (47.3%) in the secukinumab group (adjusted risk difference, 23.7; 95% CI, 17.0 to 30.4; P<0.001). Oral candidiasis occurred more often with bimekizumab (72 patients, 19.3%) than with secukinumab (11 patients, 3.0%)., Conclusions: In patients with moderate-to-severe psoriasis, treatment with bimekizumab resulted in greater skin clearance than treatment with secukinumab over 16 and 48 weeks but was associated with oral candidiasis (predominantly mild or moderate as recorded by the investigator). Longer and larger trials are required to determine the comparative effect and risks of interleukin-17 inhibitors in psoriasis. (Funded by UCB Pharma; BE RADIANT ClinicalTrials.gov number, NCT03536884.)., (Copyright © 2021 Massachusetts Medical Society.)

Background: Atopic dermatitis (AD) is associated with a substantial burden on quality of life (QoL)., Objective: To evaluate the effects of tralokinumab on health-related QoL in patients with moderate-to-severe AD using patient-reported outcomes., Methods: This was a phase 2b, randomized, double-blind, placebo-controlled, dose-ranging study in adults with moderate-to-severe AD. The patients received subcutaneous tralokinumab or placebo (1:1:1:1) every 2 weeks for 12 weeks and class 3 topical corticosteroid cream or ointment at least once daily from the run-in to end of follow-up. Patient-reported outcome end points were change from baseline to week 12 in the Dermatology Life Quality Index (dermatology life quality index (DLQI); prespecified secondary objective), the Short Form 36 Health Survey (SF-36) version 2, and sleep interference numeric rating scale score (prespecified exploratory objectives)., Results: A total of 204 patients were randomized to placebo (n = 51) or tralokinumab (45 mg, n = 50; 150 mg, n = 51; 300 mg, n = 52). Tralokinumab 300 mg every 2 weeks improved total Dermatology Life Quality Index vs placebo at week 12 (placebo-adjusted mean change, -3.51 [95% confidence interval, -6.00 to -1.02]). At week 12, both the mental component summary (4.23 [0.98-7.47]) and the physical component summary (4.26 [1.83-6.69]) and all 8 domains of the Short Form 36 Health Survey were improved in patients treated with tralokinumab 300 mg vs placebo. Sleep interference was improved at week 12 with all tralokinumab doses vs placebo., Conclusion: Tralokinumab improved health-related QoL in patients with moderate-to-severe atopic dermatitis, providing further evidence of the value of targeting interleukin-13 in such patients., Trial Registration: ClinicalTrials.gov identifier: NCT02347176; https://clinicaltrials.gov/ct2/show/NCT02347176., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Summary: Background: ABP 501, a U.S.A. Food and Drug Administration‐ and European Medicines Agency‐approved biosimilar, is highly similar to adalimumab in structure, function and pharmacokinetics. Objectives: To demonstrate similarity in efficacy, safety and immunogenicity of ABP 501 vs. adalimumab for moderate‐to‐severe plaque psoriasis (clinical trial: NCT01970488). Methods: Patients were randomized (1 : 1) to receive ABP 501 or adalimumab 40 mg every 2 weeks for 16 weeks. At week 16, patients with ≥ 50% improvement from baseline in Psoriasis Area and Severity Index (PASI) score were eligible to continue to week 52. Patients receiving ABP 501 continued; adalimumab patients were rerandomized (1 : 1) to continue adalimumab or undergo a single transition to ABP 501. Key efficacy assessments included percentage PASI improvement from baseline, PASI responders and mean change in affected body surface area from baseline to weeks 16, 32 and 50. Safety was monitored via adverse events (AEs) and antidrug antibodies (ADAs) were assessed. Results: A total of 308 patients were rerandomized at week 16 (ABP 501/ABP 501, n = 152; adalimumab/adalimumab, n = 79; adalimumab/ABP 501, n = 77). PASI percentage improvements from baseline were similar across groups for weeks 16, 32 and 50 (range: 85·8–88·2%), with no significant differences detected across groups in percentages of PASI 50, 75, 90 and 100 responders. Changes from baseline in percentage body surface area affected were similar across groups and time points. No new safety signals were detected. AEs were balanced between groups. Percentages of patients with binding and neutralizing ADAs were similar across treatments. Conclusions: ABP 501 and adalimumab have similar clinical efficacy, safety and immunogenicity profiles over 52 weeks, including after single transition, in this patient population. [ABSTRACT FROM AUTHOR]

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.

Background: Tapinarof is a topical therapeutic aryl hydrocarbon receptor modulating agent under investigation for atopic dermatitis (AD) and psoriasis treatment., Methods: A phase 2b, double-blind, vehicle-controlled study randomly assigned adolescents and adults with AD to receive tapinarof cream 0.5%, 1%, or vehicle, once or twice daily, for 12 weeks with a 4-week follow-up. Outcomes included Investigator Global Assessment (IGA), Eczema Area and Severity Index (EASI), body surface area affected, pruritus numeric rating scale scores, patients' impressions of AD and pruritus symptom severity, and Patient-Oriented Eczema Measure (POEM) scores., Results: Overall, 191 of 247 randomized patients completed the study. Week 12 IGA responses were higher in the tapinarof groups versus the vehicle group, reaching statistical significance with tapinarof 1% twice daily, ≥75%/90% improvement in EASI from baseline were significantly higher in the tapinarof groups (except 0.5% once daily and 0.5% twice daily), EASI scores were significantly improved in all tapinarof groups, and body surface area affected was significantly reduced in the tapinarof groups (except 0.5% twice daily). More patients reported AD and pruritus symptom severity as very/moderately improved in tapinarof groups, and POEM improvements were observed in all groups. Most adverse events were mild or moderate., Limitations: Larger prospective studies are required to confirm the reported analyses., Conclusions: Tapinarof is a potential important advance in topical medicine development for AD., (Copyright © 2020 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Psoriasis is commonly classified as either mild or moderate to severe, without specific parameters to differentiate moderate versus severe disease. This may lead to patients with moderate psoriasis being underrecognized and undertreated., Objective: An online survey was conducted to assess Canadian dermatologists&rsquo; perspectives on the definition and treatment of psoriasis., Method: Dermatologists included in the survey were regional and national leaders with expertise in psoriasis. Questions were developed based on feedback from a steering committee of Canadian dermatologists., Results: Of 88 dermatologists contacted, 69 responded; 42.0% were in practice for &gt;20 years. Most dermatologists reported using the percentage of psoriasis-affected body surface area (BSA) to describe disease severity (90.8% for moderate and 87.5% for severe psoriasis). The lower and upper median cutoffs for moderate psoriasis were reported as 5.0% and 10.0% for BSA and 7.0 and 11.5 for the Dermatology Life Quality Index. Most dermatologists also consider psoriasis location (eg, palms, scalp, genital area, face) as an important indicator of disease severity. The majority of Canadian dermatologists (87.5%) identified access to treatment as one of the biggest challenges for patients with moderate psoriasis. Most dermatologists estimated that &le;40% of their patients with moderate plaque psoriasis were being treated with traditional oral systemics, targeted oral systemics, or biologics., Conclusions: This is the first survey of Canadian dermatologists on moderate psoriasis. Efforts are needed to implement a clinically useful definition of moderate plaque psoriasis to improve patient care and to raise awareness of the definition among regulatory agencies and reimbursement authorities. J Drugs Dermatol. 2021;20(2):126-132. doi:10.36849/JDD.5531.

Summary: Background: The relevance of granulocyte–macrophage colony‐stimulating factor (GM‐CSF) in the management of psoriasis has not been studied previously. GM‐CSF is important in the initiation and maintenance of chronic inflammatory processes. Objectives: To investigate the clinical use of GM‐CSF neutralization by evaluating the efficacy and safety of namilumab (AMG203), a monoclonal antibody GM‐CSF inhibitor, in patients with moderate‐to‐severe plaque psoriasis. Methods: A phase II, multicentre, randomized, double‐blind, placebo‐controlled, parallel‐group, dose‐finding, proof‐of‐concept study (NEPTUNE) was conducted. Four doses of namilumab (20, 50, 80 and 150 mg, via subcutaneous injection) were compared with placebo. Assessment of the primary end point – the proportion of patients achieving ≥ 75% reduction in Psoriasis Area and Severity Index (PASI 75 treatment response) – was performed at week 12. Exploratory investigation at the tissue level was conducted in a subset of the overall study population. The trial was registered with the number NCT02129777. Results: In total, 122 patients were enrolled and 106 (86·9%) completed the double‐blind treatment; 16 (13·1%) prematurely discontinued study medication. Serum concentration–time profiles were as expected for subcutaneous delivery of an IgG1 monoclonal antibody, and exposure increased proportionally with dose elevation. The number of patients showing PASI 75 treatment response at week 12 was low in all groups; no significant difference was recorded in this end point between placebo and any namilumab group. Similar outcomes were recorded for other clinical study end points. Moreover, no significant treatment‐related changes from baseline were observed in laboratory investigations of cell types or subpopulations, or cytokines relevant to inflammatory pathways in psoriasis. Conclusions: GM‐CSF blockade is not critical for suppression of key inflammatory pathways underlying psoriasis. What's already known about this topic? Blockade of granulocyte–macrophage colony‐stimulating factor (GM‐CSF) signalling is effective in rheumatoid arthritis.Potential relevance for psoriasis has been indicated by the presence of GM‐CSF in psoriasis‐related skin blister fluid and the serum of patients with psoriasis, and also by elevated expression in psoriatic skin lesions. What does this study add? This is the first clinical investigation into the efficacy and safety of an anti‐GM‐CSF antibody in plaque psoriasis.This study provides no evidence of benefit for GM‐CSF neutralization in the treatment of plaque psoriasis.Safety profiles were comparable in the placebo and anti‐GM‐CSF treatment groups, and no incidences of pulmonary alveolar proteinosis or clinically significant changes in lung function were recorded throughout the short‐term duration of study treatment.Overall, the findings point to key differences in the role of GM‐CSF in the pathogeneses of psoriasis and rheumatoid arthritis. Linked Comment: Crowley. Br J Dermatol 2019; 180:1286–1287. Plain language summary available online Respond to this article [ABSTRACT FROM AUTHOR]

Background: Efficacy of tildrakizumab for plaque psoriasis was demonstrated in randomized, placebo‐controlled trials. Objective: To consolidate tildrakizumab efficacy results by pooling data. Methods: Data (N = 2081) from tildrakizumab 100 mg, tildrakizumab 200 mg and placebo groups in three trials were pooled. Results: Proportions of Psoriasis Area and Severity Index (PASI) 75 responders at week 12 were better with tildrakizumab 100 mg (62.3%) and tildrakizumab 200 mg (64.8%) vs. placebo (5.6%; P < 0.0001) and for PASI 90, PASI 100 and Physician's Global Assessment (PGA) 'clear' or 'minimal' vs. placebo (P < 0.0001). Responses increased from weeks 12 to 28. Week 12 PASI and PGA responses to tildrakizumab vs. placebo were numerically greater in patients with lower vs. higher bodyweight and were better with tildrakizumab 200 mg than tildrakizumab 100 mg for patients with higher bodyweight. Week 12 PASI 75 responses vs. placebo with tildrakizumab 100 mg were similar between patients with (55.0%) or without (56.7%) prior biologics. PASI 90, PASI 100 and PGA responses were generally higher in patients without prior biologics. Week 8 PASI 50 response predicted PASI 90 response. Conclusion: Pooled data confirmed the efficacy of tildrakizumab for moderate‐to‐severe plaque psoriasis. [ABSTRACT FROM AUTHOR]

The Janus kinases (JAK) are a group of molecules, composed of JAK1, JAK2, JAK3, and tyrosine kinase 2 (TYK2), which are key components within the JAK-signal transducers and activators of transcription pathway, where cytokine receptor signaling takes place. These molecules play a foundational role in the underlying pathogenesis of multiple immune-related conditions such as atopic dermatitis (AD), rheumatoid arthritis, psoriatic arthritis, inflammatory bowel disease, and others. Thus far, JAK inhibitors for inflammatory conditions have only been marketed for the treatment of rheumatoid arthritis and psoriatic arthritis, but ongoing phase II and phase III clinical trials for other immune-mediated diseases, such as AD, have also shown promising results. This review summarizes the clinical data available from various trials and reports on the safety and efficacy of abrocitinib, baricitinib, and upadacitinib, the three oral systemic JAK inhibitors used in the treatment of AD. The safety and efficacy of JAK inhibitors for the treatment of AD are emerging in the literature. It is important that dermatologists are aware of any potential adverse events or risks associated with the use of JAK inhibitors in order to promote a higher standard of treatment and quality of living., Competing Interests: Disclosure and potential conflicts of interest: KF, KM, and NN declare no conflicts of interest. MG has been an investigator, speaker, consultant or advisory board member for AbbVie, Amgen, Akros, Arcutis, Boehringer Ingelheim, BMS, Celgene, Dermira, Dermavant, Galderma, GSK, Eli Lilly, Incyte, Janssen, Kyowa Kirin, Leo Pharma, Medimmune, Merck, Novartis, Pfizer, Regeneron, Sanofi Genzyme, Sun Pharma, UCB, and Valeant/Bausch. The International Committee of Medical Journal Editors (ICMJE) Potential Conflicts of Interests form for the authors is available for download at: https://www.drugsincontext.com/wp-content/uploads/2020/10/dic.2020-8-5-COI.pdf, (Copyright © 2020 Nezamololama N, Fieldhouse K, Metzger K, Gooderham M.)

Background: Children with severe atopic dermatitis (AD) have limited treatment options., Objective: We report the efficacy and safety of dupilumab + topical corticosteroids (TCS) in children aged 6-11 years with severe AD inadequately controlled with topical therapies., Methods: In this double-blind, 16-week, phase 3 trial (NCT03345914), 367 patients were randomized 1:1:1 to 300 mg dupilumab every 4 weeks (300 mg q4w), a weight-based regimen of dupilumab every 2 weeks (100 mg q2w, baseline weight <30 kg; 200 mg q2w, baseline weight ≥30 kg), or placebo; with concomitant medium-potency TCS., Results: Both the q4w and q2w dupilumab + TCS regimens resulted in clinically meaningful and statistically significant improvement in signs, symptoms, and quality of life (QOL) versus placebo + TCS in all prespecified endpoints. For q4w, q2w, and placebo, 32.8%, 29.5%, and 11.4% of patients, respectively, achieved Investigator's Global Assessment scores of 0 or 1; 69.7%, 67.2%, and 26.8% achieved ≥75% improvement in Eczema Area and Severity Index scores; and 50.8%, 58.3%, and 12.3% achieved ≥4-point reduction in worst itch score. Response to therapy was weight-dependent: optimal dupilumab doses for efficacy and safety were 300 mg q4w in children <30 kg and 200 mg q2w in children ≥30 kg. Conjunctivitis and injection-site reactions were more common with dupilumab + TCS than with placebo + TCS., Limitations: Short-term 16-week treatment period; severe AD only., Conclusion: Dupilumab + TCS is efficacious and well tolerated in children with severe AD, significantly improving signs, symptoms, and QOL., (Copyright © 2020 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Importance: Abrocitinib, an oral, once-daily Janus kinase 1 selective inhibitor, was effective and well tolerated in a phase 3 monotherapy trial of patients with moderate-to-severe atopic dermatitis (AD)., Objective: To investigate the efficacy and safety of abrocitinib in adolescents and adults with moderate-to-severe AD in an identically designed trial., Design, Setting, and Participants: This phase 3, double-blinded, placebo-controlled, parallel-group randomized clinical trial included patients 12 years or older with a clinical diagnosis of moderate-to-severe AD for at least 1 year and inadequate response to topical medications given for at least 4 weeks within 6 months. Patients were enrolled from 115 centers in Australia, Bulgaria, Canada, China, Czechia, Germany, Hungary, Japan, South Korea, Latvia, Poland, United Kingdom, and the United States from June 29, 2018, to August 13, 2019. Data were analyzed from September 13 to October 25, 2019., Interventions: Patients were randomly assigned (2:2:1) to receive once-daily oral abrocitinib in 200- or 100-mg doses or placebo for 12 weeks., Main Outcomes and Measures: The coprimary end points were the proportion of patients achieving Investigator Global Assessment (IGA) response (ie, clear [0] or almost clear [1], with improvement of ≥2 grades) and the proportion of patients achieving at least 75% improvement in Eczema Area and Severity Index score (EASI-75) at week 12. Key secondary end points included the proportion of patients achieving a Peak Pruritus Numerical Rating Scale (PP-NRS) response (ie, improvement of ≥4 points) at week 12. Other secondary end points included the proportion of patients achieving at least 90% improvement in EASI score (EASI-90). Safety was assessed via adverse events and laboratory monitoring., Results: A total of 391 patients (229 male [58.6%]; mean [SD] age, 35.1 [15.1] years) were included in the analysis; of these, 155 received abrocitinib, 200 mg/d; 158, abrocitinib, 100 mg/d; and 78, placebo. Among patients with available data at week 12, greater proportions of patients in the 200- and 100-mg abrocitinib groups vs the placebo group achieved IGA (59 of 155 [38.1%] and 44 of 155 [28.4%] vs 7 of 77 [9.1%]; P < .001) and EASI-75 (94 of 154 [61.0%] and 69 of 155 [44.5%] vs 8 of 77 [10.4%]; P < .001), greater estimated proportions achieved PP-NRS (55.3% [95% CI, 47.2%-63.5%] and 45.2% [95% CI, 37.1%-53.3%] vs 11.5% [95% CI, 4.1%-19.0%]; P < .001), and/or greater proportions achieved EASI-90 (58 of 154 [37.7%] and 37 of 155 [23.9%] vs 3 of 77 [3.9%]) responses. Adverse events were reported for 102 patients (65.8%) in the 200-mg group, 99 (62.7%) in the 100-mg group, and 42 (53.8%) in the placebo group; serious adverse events were reported for 2 patients (1.3%) in the 200-mg group, 5 (3.2%) in the 100-mg group, and 1 (1.3%) in the placebo group. Decreases in platelet count (2 [1.3%]) and laboratory values indicating thrombocytopenia (5 [3.2%]) were reported in the 200-mg group., Conclusions and Relevance: Monotherapy with once-daily oral abrocitinib was effective and well tolerated in adolescents and adults with moderate-to-severe AD., Trial Registration: ClinicalTrials.gov Identifier: NCT03575871.

Background: Roflumilast cream (ARQ-151) is a highly potent, selective phosphodiesterase-4 inhibitor in development for once-daily topical treatment of chronic plaque psoriasis. Objectives: To assess the safety and efficacy of once-daily roflumilast cream 0.5% and 0.15% in patients with chronic plaque psoriasis. Methods: This phase 1/2a study enrolled a single-dose, open-label cohort (Cohort 1: 0.5% cream applied to 25 cm² psoriatic plaques), and a 28-day, double-blinded cohort (Cohort 2: 1:1:1 randomization to roflumilast cream 0.5%, 0.15%, or vehicle). Patients had chronic plaque psoriasis of >6 months' duration with ≤5% body surface area involvement. Outcomes included safety (adverse events) and efficacy (percentage change in the Target Plaque Severity Score [TPSS] × Target Plaque Area [TPA]) at week 4. Results: For Cohorts 1 (n=8) and 2 (n=89), adverse events (all mild/moderate; none severe or serious) were similar between active arms and vehicle. Treatment-related events were confined to the application site, without differences between drug and vehicle. No patient discontinued treatment due to adverse events. The primary efficacy endpoint was met for both roflumilast cream doses: TPSS×TPA improvement at week 4 was statistically significant for roflumilast 0.5% (P=0.0007) and 0.15% (P=0.0011) versus vehicle; significance was reached as early as 2 weeks. For both roflumilast cream doses, 66%-67% improvement from baseline was observed at week 4, without reaching a plateau, versus 38% improvement for vehicle. Conclusion: Roflumilast cream was safe and highly effective at doses of 0.5% and 0.15% and represents a potential novel once-daily topical therapy for the treatment of chronic plaque psoriasis. ClinicalTrials.gov NCT03392168. J Drugs Dermatol. 2020;19(8): doi:10.36849/JDD.2020.5370.

Background: Omalizumab shows greater clinical benefit with 300 mg dose than with the 150 mg dose., Objective: To determine outcomes postwithdrawal, relapse, and re-treatment in omalizumab responders, and from stepping up to 300 mg after insufficient symptom control with 150 mg., Methods: This was a prospective, randomized (3:4), open-label, noncomparator study (clinicaltrials.gov: NCT02161562). A total of 314 adult patients with chronic spontaneous urticaria and symptomatic on H 1 -antihistamines were enrolled between August 1, 2014, and November 6, 2015. Patients received 150 mg/300 mg omalizumab, every 4 weeks for 24 weeks. Omalizumab 150 mg dose could be stepped up to 300 mg between week 8 and week 24, if the 7-day sum of the daily Urticaria Activity Score (UAS7) was more than 6. If patients relapsed after treatment withdrawal at week 24, they could be re-treated with the same dose on which omalizumab was started. Patients on 300 mg could extend treatment by 12 weeks if they did not achieve symptom control on 300 mg in the initial dosing phase. The primary end point was the proportion of well-controlled patients who relapsed postwithdrawal, and achieved symptom control at the end of re-treatment. Symptom control was assessed using UAS7 (UAS7 ≤ 6 = well controlled)., Results: Overall, 115 of 314 patients had adequate symptom control at week 24 (end of the initial dosing period) and 56 were re-treated after relapse postwithdrawal; 87.8% (95% CI, 78.6%-96.9%) regained symptomatic control (UAS7 ≤ 6). Most (141 of 178) patients initially treated with 150 mg required step-up to 300 mg, which resulted in a 9.5-point (95% CI, 7.6-11.3) improvement in UAS7 over the mean change observed initially on 150 mg., Conclusions: Step-up to 300 mg helps a greater proportion of patients achieve symptom control, and re-treatment with omalizumab is as effective as initial therapy., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: Ixekizumab, a high-affinity monoclonal antibody that selectively targets interleukin-17A, is approved for treatment of moderate-to-severe plaque psoriasis. Our objective was to evaluate the long-term efficacy and safety of ixekizumab in moderate-to-severe plaque psoriasis through 5 years., Methods: Data were integrated from the UNCOVER-1 and UNCOVER-2, randomized, double-blinded, phase-3 trials. Patients who continuously received the labeled ixekizumab dose, were static Physician's Global Assessment (sPGA) (0,1) responders at Week 12 and completed 60 weeks of treatment could enter the long-term extension (LTE) period. Patients could escalate to every-2-week dosing per investigator opinion. Efficacy and health outcomes included proportion of patients achieving Psoriasis Area and Severity Index (PASI) 75/90/100, sPGA (0,1) and (0), absolute PASI ≤ 5/ ≤ 3/ ≤ 2/ ≤ 1 and Dermatology Life Quality Index (DLQI) (0,1). Results exclude patients who escalated to every-2-week dosing. A modified non-responder imputation method was used to account for missing data. Supplemental analyses include patients who escalated to every-2-week dosing and observed and multiple imputation results. Exposure-adjusted safety outcomes are also reported., Results: Of 206 patients who entered the LTE periods, 172 completed treatment. At Week 60, PASI 75/90/100 responses were 94.7%, 85.0% and 62.1%, respectively, and at year 5 were 90.3%, 71.3% and 46.3%, respectively. Similarly, meaningful responses were achieved for the other efficacy and health measures. Among patients with PASI 100 through 5 years, 92% achieved DLQI (0,1), indicating no impact of skin disease on quality of life. During the LTE period, exposure-adjusted incidence rates were 31.4 per 100 patient-years for treatment-emergent adverse events and 6.8 per 100 patient-years for serious adverse events. No deaths were reported. No new or unexpected safety findings were noted., Conclusions: The results demonstrate 80 mg ixekizumab maintains long-term efficacy and a safety profile consistent with previous data in patients with moderate-to-severe plaque psoriasis through 5 years of treatment., Trial Registration: ClinicalTrials.gov identifier, UNCOVER-1: NCT01474512, UNCOVER-2: NCT01597245.

Importance: Risankizumab selectively inhibits interleukin 23, a cytokine that contributes to psoriatic inflammation., Objective: To evaluate the efficacy and safety of risankizumab vs placebo and continuous treatment vs withdrawal in adults with moderate to severe plaque psoriasis., Design, Setting, and Participants: Multinational, phase 3, randomized, double-blind, placebo-controlled trial conducted from March 6, 2016, to July 26, 2018. A total of 507 eligible patients had stable moderate to severe chronic plaque psoriasis for 6 months or longer, body surface area involvement greater than or equal to 10%, Psoriasis Area and Severity Index (PASI) greater than or equal to 12, and a static Physician's Global Assessment (sPGA) score greater than or equal to 3. Intention-to-treat analysis was conducted., Interventions: Patients were randomized (4:1, interactive response technology) to risankizumab, 150 mg, subcutaneously, or placebo at weeks 0 and 4 (part A1). All patients received risankizumab at week 16. At week 28, patients randomized to risankizumab who achieved an sPGA score of 0/1 were rerandomized 1:2 to risankizumab or placebo every 12 weeks (part B)., Main Outcomes and Measures: Co-primary end points for the part A1 phase included proportions of patients achieving greater than or equal to 90% improvement in PASI (PASI 90) and sPGA score of 0/1 at week 16. The PASI measures severity of erythema, infiltration, and desquamation weighted by area of skin involvement over the head, trunk, upper extremities, and lower extremities; scores range from 0 (no disease) to 72 (maximal disease activity). The sPGA assesses average thickness, erythema, and scaling of all psoriatic lesions; scores range from 0 (clear) to 4 (severe), with 0/1 indicating clear or almost clear. Primary and secondary end points in part B included proportion of rerandomized patients achieving an sPGA score of 0/1 at week 52 (primary) and week 104 (secondary)., Results: Of 563 patients screened, 507 were randomized to risankizumab (n = 407) or placebo (n = 100). Most patients were men (356 [70.2%]); median age was 51 years (interquartile range, 38-60 years). At week 16, 298 patients (73.2%) in the treatment group vs 2 patients (2.0%) receiving placebo achieved a PASI 90 response, and 340 patients (83.5%) receiving risankizumab vs 7 patients (7.0%) receiving placebo achieved sPGA 0/1 scores (placebo-adjusted differences: PASI 90: 70.8%; 95% CI, 65.7%-76.0%; sPGA 0/1: 76.5%; 95% CI, 70.4%-82.5%; P < .001 for both). At week 28, 336 responders were rerandomized to risankizumab (n = 111) or treatment withdrawal (n = 225). At week 52, the sPGA 0/1 score was achieved by 97 patients (87.4%) receiving risankizumab vs 138 patients (61.3%) receiving placebo. At week 104, the sPGA 0/1 score was achieved by 90 patients (81.1%) receiving risankizumab vs 16 patients (7.1%) receiving placebo (placebo-adjusted differences: week 52: 25.9%; 95% CI, 17.3%-34.6%; week 104: 73.9%; 95% CI, 66.0%-81.9%; P < .001 for both). Rates of treatment-emergent adverse events were similar between risankizumab (186 [45.7%]) and placebo (49 [49.0%]) in part A1 and remained stable over time., Conclusions and Relevance: Risankizumab showed superior efficacy compared with placebo through 16 weeks and treatment withdrawal through 2 years. Risankizumab was well tolerated, with no unexpected safety findings during the 2-year trial., Trial Registration: ClinicalTrials.gov Identifier: NCT02672852.

Background: Cumulative clinical improvement and speed of improvement are important to psoriasis patients., Objective: Compare cumulative benefits of biologics over 12 to 16 weeks in the treatment of moderate to severe psoriasis., Methods: A systematic literature review identified phase III trial data on Psoriasis Area and Severity Index (PASI) responses for biologics during 12 and 16 weeks of treatment. Cumulative clinical benefit, measured by the area under the curve for PASI ≥75% improvement (PASI 75), ≥90% improvement (PASI 90), and 100% improvement (PASI 100), was compared using the network meta-analysis and Bayesian methodology on the relative probability of achieving percentage of maximum area under the curve., Results: Among biologics approved for psoriasis treatment, anti-interleukin-17 biologics demonstrated consistently greater cumulative clinical benefits on PASI 75, PASI 90, and PASI 100 over the 12- or 16-week period than anti-interleukin-23 and other biologics. For biologics with 12-week data, ixekizumab and brodalumab showed greater cumulative benefits for PASI 75, PASI 90, and PASI 100 than secukinumab, followed by guselkumab, infliximab, adalimumab, ustekinumab, and etanercept. Ixekizumab showed greater cumulative benefits than all other biologics reporting 16-week data., Limitations: Recently approved biologics were not included., Conclusion: Ixekizumab (at 12 weeks and 16 weeks) and brodalumab (at 12 weeks) had greater cumulative clinical benefit than all of other biologics studied., (Copyright © 2019 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Randomized controlled studies of combination therapies in rosacea are limited., Objective: Evaluate the efficacy and safety of combining ivermectin 1% cream (IVM) and doxycycline 40-mg modified-release capsules (ie, 30-mg immediate-release and 10-mg delayed-release beads) (DMR) versus IVM and placebo for treatment of severe rosacea., Methods: This 12-week, multicenter, randomized, investigator-blinded, parallel-group comparative study randomized adult subjects with severe rosacea (Investigator's Global Assessment [IGA] score, 4) to receive either IVM and DMR (combination arm) or IVM and placebo (monotherapy)., Results: A total of 273 subjects participated. IVM and DMR displayed superior efficacy in reduction of inflammatory lesions (-80.3% vs -73.6% for monotherapy [P = .032]) and IGA score (P = .032). Combination therapy had a faster onset of action as of week 4; it significantly increased the number of subjects achieving an IGA score of 0 (11.9% vs 5.1% [P = .043]) and 100% lesion reduction (17.8% vs 7.2% [P = .006]) at week 12. Both treatments reduced the Clinician's Erythema Assessment score, stinging/burning, flushing episodes, Dermatology Life Quality Index score, and ocular signs/symptoms and were well tolerated., Limitations: The duration of the study prevented evaluation of potential recurrences or further improvements., Conclusion: Combining IVM and DMR can produce faster responses, improve response rates, and increase patient satisfaction in cases of severe rosacea., (Copyright © 2019 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Introduction: Long-term safety data are critical for evaluating therapies for psoriasis. Ixekizumab has demonstrated efficacy and is well tolerated for the treatment of moderate-to-severe plaque psoriasis. We examined the safety and tolerability of up to 5 years of ixekizumab therapy in patients with psoriasis., Methods: Integrated safety data were analyzed from 13 ixekizumab clinical studies. Rates of treatment-emergent adverse events (TEAEs), serious AEs (SAEs) and AEs of special interest were analyzed for the 12-week induction period in the combined pivotal studies, and for all pooled studies by year(s) of therapy and overall, reported as exposure-adjusted incidence rates (IRs) per 100 patient-years (p-y) and/or frequencies., Results: Total ixekizumab exposure was 17,003.4 p-y (N = 5898); 2749 patients had ≥ 4 years of exposure. When compared across years of exposure, rates for AEs remained largely stable or declined, including TEAEs leading to discontinuation (3.8/100 p-y in year 1, declining to 2.0/100 p-y in year 5); SAEs (range 6.2-7.0/100 p-y); serious infections (range 1.3-1.7/100 p-y); nonmelanoma skin cancer (ranging from 0.5/100 p-y in year 1 to 0.2/100 p-y in years 4-5); other malignancies (range 0.4-0.6/100 p-y); inflammatory bowel disease including ulcerative colitis and Crohn's disease (IR 0.2/100 p-y); and major adverse cardiovascular events (MACE) (range 0.3-0.7/100 p-y). Candidiasis was reported in 327 patients (IR 1.9/100 p-y), with the majority identified as mucocutaneous. The rate of injection site reactions was 15.5/100 p-y during year 1 and 2.0-2.3/100 p-y by years 3-5., Conclusions: The decrease in rates of TEAEs and the stable rates of SAEs, other malignancies and MACE during up to 5 years of ixekizumab dosing are consistent with previous reports describing a favorable safety profile of ixekizumab following shorter durations of exposure., Funding: Eli Lilly and Company.

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.)

This is the English version of the 2024 clinical practice guidelines for the management of atopic dermatitis (AD). AD is a disease characterized by relapsing eczema with pruritus as a primary lesion. A crucial aspect of AD treatment is the prompt induction of remission via the suppression of existing skin inflammation and pruritus. To achieve this, topical anti-inflammatory drugs, such as topical corticosteroids, tacrolimus ointment, delgocitinib ointment, and difamilast ointment, have been used. However, the following treatments should be considered in addition to topical therapy for patients with refractory moderate-to-severe AD: oral cyclosporine, subcutaneous injections of biologics (dupilumab, nemolizumab, tralokinumab), oral Janus kinase inhibitors (baricitinib, upadacitinib, abrocitinib), and phototherapy. In these revised guidelines, descriptions of five new drugs, namely, difamilast, nemolizumab, tralokinumab, upadacitinib, and abrocitinib, have been added. The guidelines present recommendations to review clinical research articles, evaluate the balance between the advantages and disadvantages of medical activities, and optimize medical activity-related patient outcomes with respect to several important points requiring decision-making in clinical practice., (© 2024 Japanese Dermatological Association.)

This study systematically reviews existing data on the efficacy of Tyrosine Kinase 2 (TYK2) inhibitors in comparison to placebo or standard treatments for therapeutic benefit and improving quality of life in dermatological diseases. Seventeen records representing 13 clinical trials, one matching-adjusted indirect comparison, and one case study were included. Results indicate that Deucravacitinib is superior to placebo, Apremilast and Adalimumab in treating adult patients with moderate-to-severe plaque psoriasis and superior to placebo in the treatment of adults with systemic lupus erythematosus. Comparative investigations on Brepocitinib and Ropsacitinib were more limited. Oral Brepocitinib demonstrated superiority over placebo in managing alopecia areata, and hidradenitis suppurativa. Topical Brepocitinib exhibited superiority over placebo in treating atopic dermatitis, but not plaque psoriasis. Ropsacitinib demonstrated superiority over placebo in the management of plaque psoriasis. Brepocitinib and Ropsacitinib had more side effects than Deucravacitinib., (© 2024 Australasian College of Dermatologists.)

Purpose: We report a unique case of significant human papillomavirus-associated conjunctival papillomas and severe corneal ulceration leading to corneal perforation in a patient treated with dupilumab for atopic dermatitis., Methods: This study is a case report and literature review of severe corneal side effects related to dupilumab., Results: A 27-year-old man with severe atopic dermatitis and no ocular history was administered dupilumab 300 mg via subcutaneous injections every 2 weeks with an excellent response. Following the onset of treatment, the patient developed conjunctivitis, conjunctival papillomas, and dry eyes, which were initially treated with lubricating eye drops. Fourteen months after commencing dupilumab, he had a rapid onset of painful visual loss in the OD accompanied by severe bilateral conjunctival injection and was found to have a central corneal ulcer and diffuse papillomas on the palpebral and bulbar conjunctiva. Despite management with intravenous methylprednisolone and topical dexamethasone, the patient's corneal ulcer progressed to a corneal melt, resulting in perforation 2 months after diagnosis, which necessitated a corneal graft., Conclusions: We present the third reported case of dupilumab-associated corneal perforation and the first case to our knowledge of dupilumab-associated conjunctival papillomas. As dupilumab usage increases, awareness of these potential complications among prescribers is essential., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: For patients with psoriasis, discontinuation of biologics following remission has become more common in daily practice., Objective: We aimed to identify predictors and construct a predictive model for time to relapse following withdrawal from biologics., Methods: This 12-year, multicenter, observational cohort study was performed in six dermatology centers between February 2011 and February 2024. We identified biological treatment episodes in patients with moderate-to-severe psoriasis and included only treatment episodes in which a clinical response (≥ 50% reduction in Psoriasis Area and Severity Index score [PASI 50] from baseline) was achieved and the patient withdrew from biological therapy with a well-controlled status (PASI < 10 and ≥ 50% improvement in PASI from baseline). The primary outcome was time to relapse, which was defined as the period from the last biologic administration to relapse. An extended multivariate Cox proportional hazards analysis (Prentice-Williams-Peterson Gap time model) was used to predict relapse and generate a predictive model., Results: This study screened 1613 biological treatment episodes, and 991 treatment episodes were enrolled. The time to relapse decreased significantly as the number of previous withdrawals from biological treatment increased (p < 0.001). Similarly, the time to relapse decreased significantly as the number of previous biologics used increased (p < 0.001). The maximum PASI improvement during biological treatment decreased and the PASI score at withdrawal of biological treatment increased in parallel as the number of prior withdrawals from biologics increased. The time to relapse following withdrawal was longest for interleukin (IL)-23 inhibitors (IL-23i), followed by the IL-12/23i, IL-17 inhibitors (IL-17i), and tumor necrosis factor-α inhibitors. After adjustment, multivariate Cox regression identified the following significant predictors of relapse following withdrawal: the mechanisms of action of biologics (hazard ratio [HR] for IL-17i vs IL-12/23i, 1.59; HR for IL-23i vs IL-12/23i, 0.60), number of previous withdrawals from biological treatment (HR 1.23; 95% confidence interval [CI] 1.13‒1.33), time to achieve PASI 50 (HR 1.01; 95% CI 1.00‒1.02), maximum PASI improvement on biologics (HR 0.98; 95% CI 0.98‒0.99), and PASI at the end of therapy (HR 1.03; 95% CI 1.01‒1.05). The model had good predictive and discriminative ability., Conclusions: These results have the potential to help physicians and patients make individualized treatment decisions; information on the risk of relapse of psoriasis at specific timepoints following the withdrawal of biologics is particularly valuable for patients considering discontinuation of biologics or as-needed biologic therapy. However, the benefit and risk of repeated withdrawals of biologics should be carefully weighed, as the treatment efficacy and duration of remission decline as the number of withdrawals increases., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Background: Brodalumab, a fully human monoclonal immunoglobulin IgG2 antibody that binds the human interleukin 17 receptor subunit A, is available for the treatment of moderate-to-severe plaque psoriasis in Europe since September 2017, but so far there are only a few studies on its use in real-world conditions., Objectives: To assess the management of moderate-to-severe psoriasis with brodalumab 210 mg in daily practice after 12 and 52 weeks (W). In addition, patient profiles and treatment pathways are described., Methods: LIBERO is a prospective, multicenter, non-interventional study including adult patients with plaque psoriasis treated with brodalumab 210 mg., Results: In total, 638 patients (65% male, mean age: 49.3 ± 14.4 years) from 148 sites in Germany were enrolled. The majority suffered from severe (51.1%) or very severe (13.1%) psoriasis according to physician global assessment (PGA0-5). When starting with brodalumab, 58.5% were biologic naïve and 41.5% were previously treated with another biologic, mainly adalimumab (18.5%) and secukinumab (17.9%). About 74.0% of patients met the primary endpoint of an absolute PASI ≤3 at ~W12 (n = 618, LOCF). The mean PASI was reduced significantly as of ~W2 from 17.2 (±11.7) to 9.7 (±8.8) and improved further to 3.3 (±6.3) at ~W12 (p < 0.001). At ~W52 85.5% of patients reached a PGA0/1-response (primary endpoint) and 54.1% patients were assessed as completely clear (PGA0) (both n = 399, as observed). Effectiveness of brodalumab was confirmed in relevant subgroup analysis by previous treatment regimen. Most frequently reported adverse events were nasopharyngitis (4.6%), psoriasis (4.6%) and arthralgia (4.1%), new safety signals were not detected., Conclusions: This representative, non-interventional study confirms the short- and long-term effectiveness and safety profile of brodalumab in the management of psoriasis in daily practice as well as in relevant treatment pathways., (© 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.)

Background Despite unmet need, 15 years have passed since a topical therapy with a new mechanism of action for atopic dermatitis ( AD) has been approved. Janus kinase ( JAK) inhibitor treatment effect via topical application in patients with AD is unknown. Objectives Tofacitinib, a small-molecule JAK inhibitor, was investigated for the topical treatment of AD. Methods In this 4-week, phase IIa, randomized, double-blind, vehicle-controlled study ( NCT02001181), 69 adults with mild-to-moderate AD were randomized 1:1 to 2% tofacitinib or vehicle ointment twice daily. Percentage change from baseline ( CFB) in Eczema Area and Severity Index ( EASI) score at week 4 was the primary end point. Secondary efficacy end points included percentage CFB in body surface area ( BSA), CFB in EASI Clinical Signs Severity Sum Score, proportion of patients with Physician's Global Assessment ( PGA) response and CFB in patient-reported pruritus. Safety, local tolerability and pharmacokinetics were monitored. Results The mean percentage CFB at week 4 in EASI score was significantly greater ( P < 0·001) for tofacitinib (−81·7%) vs. vehicle (−29·9%). Patients treated with tofacitinib showed significant ( P < 0·001) improvements vs. vehicle across all prespecified efficacy end points and for pruritus at week 4. Significant improvements in EASI, PGA and BSA were observed by week 1 and improvements in pruritus were observed by day 2. Safety/local tolerability were generally similar for both treatments, although more adverse events were observed for vehicle vs. tofacitinib. Conclusions Tofacitinib ointment showed significantly greater efficacy vs. vehicle across end points, with early onset of effect and comparable safety/local tolerability to vehicle. JAK inhibition through topical delivery is potentially a promising therapeutic target for AD. [ABSTRACT FROM AUTHOR]