Importance Alopecia areata (AA) is a chronic, systemic immune-mediated disease characterized by nonscarring hair loss. Many patients do not experience improvements with available treatment options and only ritlecitinib is approved for adolescent patients; therefore, there remains a clear unmet need for additional and improved systemic therapies. Objective To evaluate the efficacy and safety of upadacitinib—an oral selective Janus kinase inhibitor—in adult and adolescent patients with severe AA. Design, Setting, and Participants This global clinical program included 2 parallel phase 3 replicate randomized clinical trials (UP-AA1 and UP-AA2) conducted from October 2023 to July 2025, to evaluate upadacitinib in adolescent and adult patients (age 12 to <64 years old) with severe AA, defined as a Severity of Alopecia Tool (SALT) score of 50 or greater. Both trials included a 24-week placebo-controlled, double-blinded treatment period (period A) and a 28-week blinded extension treatment period (period B). Data were analyzed from July 2025 to October 2025. Interventions Eligible patients were randomized 2:2:1 to once daily 15- or 30-mg upadacitinib or matching placebo. Main Outcomes and Measures Achievement of (multiplicity controlled) SALT score of 20 or less at week 24. Multiplicity-controlled secondary efficacy end points included achievement of improvements in clinician-reported outcomes for eyebrows and eyelashes; achievement of SALT scores of 20 or less at weeks 4, 8, and 12; achievement of SALT score of 10 or less; SALT score 0 at week 24; patients’ global impression of change of AA score of much better or moderately better at weeks 4 and 24; and other AA-specific health-related quality of life measures at week 24. Results A total of 1399 patients were randomized (mean [range] age, 36 [12-64] years; 826 female [59.0%]), 676 patients from the UP-AA1 and 723 patients from the UP-AA2, to either 15-mg upadacitinib (270 and 289 patients, respectively), 30-mg upadacitinib (271 and 289), or placebo (135 and 145). Their mean (SD) SALT score was 83.9 (18.9) at baseline. The proportion of patients who achieved SALT score of 20 or less at week 24 was significantly higher for the 15-mg upadacitinib (122 [45.2%] and 129 [44.6%]) and the 30-mg upadacitinib (149 [55.0%] and 157 [54.3%]) groups, respectively, than for the placebo (2 [1.5%] and 5 [3.4%]) group. The safety profile of both doses was similar in adults and adolescents and consistent with approved indications; no new safety findings were identified. Treatment-emergent adverse events reported by more than 5% of patients in any treatment group were upper respiratory tract infection, acne, elevated blood creatine phosphokinase, and nasopharyngitis. Across both studies, treatment-emergent serious adverse events occurred in 9 (1.6%), 13 (2.3%), and 1 (0.4%) of patients receiving 15-mg upadacitinib , 30-mg upadacitinib, or placebo, respectively. Conclusions and Relevance In these 2 parallel phase 3 replicate randomized clinical trials, upadacitinib demonstrated a positive benefit-risk profile in adults and adolescents with severe AA. Upadacitinib may be a potentially effective treatment option for this patient population. Trial Registration ClinicalTrials.gov Identifier: NCT06012240

Atopic dermatitis (AD) can be treated with topical or systemic therapies. Here, we review baseline disease severity and burden in clinical trials of topical and systemic therapies to describe the patient populations in which they may be effective. PubMed and the Cochrane database were searched from January 1, 2010, to May 1, 2025, to identify manuscripts reporting randomized controlled clinical trials (≥ 30 patients) of topical AD therapies, including those considered advanced (crisaborole ointment, roflumilast cream, ruxolitinib cream, tapinarof cream), and pivotal clinical trials of advanced systemic AD therapies (abrocitinib, baricitinib, dupilumab, lebrikizumab, nemolizumab, tralokinumab, upadacitinib). Results were presented descriptively using published disease severity thresholds. Included clinical trials of topical AD therapies (n = 59) reported mean assessments of baseline clinician-rated disease severity (affected body surface area [n = 38], Eczema Area and Severity Index [n = 41]), and patient-reported disease burden (itch numerical rating scale/visual analog scale [n = 35], Dermatology Life Quality Index [n = 13], Patient-Oriented Eczema Measure [n = 19]). For clinician-rated disease severity assessments, mean baseline values and SDs generally fell in the moderate categories. For patient-reported disease burden, baseline mean values fell in the moderate category, and SDs overlapped the severe or “very large effect” categories in most studies. Baseline mean values for clinician-rated disease severity measures were substantially higher in pivotal systemic therapy versus topical therapy studies, and SDs generally did not overlap. Baseline mean values for patient-reported disease burden measures were generally lower in pivotal clinical trials of advanced topical therapies versus those conducted for advanced systemic therapies, but SDs overlapped between studies for both treatment categories. Many patients with AD treated in clinical trials of topical therapies report high levels of disease burden, overlapping with some patients eligible for systemic therapies. These results suggest that advanced topical therapies may be effective in patients with more extensive AD.

Introduction Brodalumab is the only interleukin-17 (IL-17) receptor A blocker approved for moderate-to-severe plaque psoriasis and blocks downstream signaling of multiple IL-17 isoforms including IL-17A, IL-17F, IL-17C, IL-17E, and IL-17A/F. Here, we contextualize effectiveness and safety of brodalumab in adult patients in the Canadian Real-World Evidence (CARE) study alongside results from pivotal phase 3 trials. Methods CARE is a Canadian, 12-month, multi-center, prospective, observational phase 4 study (NCT05132231) in adult patients initiating brodalumab as part of routine clinical care. Results reported here reflect a prespecified interim analysis through month 6. In the AMAGINE-1, -2, and -3 phase 3 trials (NCT01708590, NCT01708603, NCT01708629), participants were initially randomized to receive brodalumab (140 or 210 mg) or placebo via subcutaneous injection every 2 weeks (Q2W) during a 12-week induction period. At week 12, brodalumab-treated patients were rerandomized to placebo or the same brodalumab dose (AMAGINE-1) or various brodalumab regimens (AMAGINE-2 and -3) through week 52. Brodalumab’s performance at the approved 210-mg dose was assessed with Psoriasis Area and Severity Index (PASI) scores and rates of adverse events (AEs). Real‑world effectiveness (3 and 6 months) and safety (6 months) are presented descriptively alongside pivotal trials efficacy and safety (3 months). No formal statistical testing was performed. Results In the CARE study, 351 patients (58% male, 74% Caucasian, mean age 51 y, baseline mean PASI score 14.1) completed the 6-month visit. At 3 months, PASI 75/90/100 were observed in 78.2% (265/339), 64.0% (217/339), and 43.4% (147/339) of patients, with improvements at 6 months to 82.1% (276/336), 72.6% (244/336), and 52.1% (175/336) of patients, respectively. Overall, 44.4% and 2.0% of patients reported AEs and serious AEs, respectively. In the phase 3 trials with brodalumab 210 mg (n=1458, 69%-73% male, 90%-91% Caucasian, mean age 45-46 y, baseline mean PASI score 19.4-20.4), PASI 75/90/100 were achieved in 83%-86%, 69%-70%, and 37%-44% of patients at 3 months (week 12). A total of 56.8%-59.0% and 1.0%-1.8% of patients experienced AEs and serious AEs, respectively. Conclusions Real‑world outcomes with brodalumab align closely with the efficacy and safety profile established in pivotal phase 3 trials. These results support the robustness and generalizability of brodalumab’s clinical profile across both controlled and routine‑care settings and its use as an effective treatment option for moderate‑to‑severe plaque psoriasis.

Importance:Alopecia areata (AA) is a chronic, systemic immune-mediated disease characterized by nonscarring hair loss. Many patients do not experience improvements with available treatment options and only ritlecitinib is approved for adolescent patients; therefore, there remains a clear unmet need for additional and improved systemic therapies. Objective:To evaluate the efficacy and safety of upadacitinib-an oral selective Janus kinase inhibitor-in adult and adolescent patients with severe AA. Design, Setting, and Participants:This global clinical program included 2 parallel phase 3 replicate randomized clinical trials (UP-AA1 and UP-AA2) conducted from October 2023 to July 2025, to evaluate upadacitinib in adolescent and adult patients (age 12 to <64 years old) with severe AA, defined as a Severity of Alopecia Tool (SALT) score of 50 or greater. Both trials included a 24-week placebo-controlled, double-blinded treatment period (period A) and a 28-week blinded extension treatment period (period B). Data were analyzed from July 2025 to October 2025. Interventions:Eligible patients were randomized 2:2:1 to once daily 15- or 30-mg upadacitinib or matching placebo. Main Outcomes and Measures:Achievement of (multiplicity controlled) SALT score of 20 or less at week 24. Multiplicity-controlled secondary efficacy end points included achievement of improvements in clinician-reported outcomes for eyebrows and eyelashes; achievement of SALT scores of 20 or less at weeks 4, 8, and 12; achievement of SALT score of 10 or less; SALT score 0 at week 24; patients' global impression of change of AA score of much better or moderately better at weeks 4 and 24; and other AA-specific health-related quality of life measures at week 24. Results:A total of 1399 patients were randomized (mean [range] age, 36 [12-64] years; 826 female [59.0%]), 676 patients from the UP-AA1 and 723 patients from the UP-AA2, to either 15-mg upadacitinib (270 and 289 patients, respectively), 30-mg upadacitinib (271 and 289), or placebo (135 and 145). Their mean (SD) SALT score was 83.9 (18.9) at baseline. The proportion of patients who achieved SALT score of 20 or less at week 24 was significantly higher for the 15-mg upadacitinib (122 [45.2%] and 129 [44.6%]) and the 30-mg upadacitinib (149 [55.0%] and 157 [54.3%]) groups, respectively, than for the placebo (2 [1.5%] and 5 [3.4%]) group. The safety profile of both doses was similar in adults and adolescents and consistent with approved indications; no new safety findings were identified. Treatment-emergent adverse events reported by more than 5% of patients in any treatment group were upper respiratory tract infection, acne, elevated blood creatine phosphokinase, and nasopharyngitis. Across both studies, treatment-emergent serious adverse events occurred in 9 (1.6%), 13 (2.3%), and 1 (0.4%) of patients receiving 15-mg upadacitinib , 30-mg upadacitinib, or placebo, respectively. Conclusions and Relevance:In these 2 parallel phase 3 replicate randomized clinical trials, upadacitinib demonstrated a positive benefit-risk profile in adults and adolescents with severe AA. Upadacitinib may be a potentially effective treatment option for this patient population. Trial Registration:ClinicalTrials.gov Identifier: NCT06012240.

The chronic hand eczema (CHE) management landscape is rapidly evolving with emerging evidence supporting the efficacy and safety of new treatments, some of which are not included in current guidelines. Preventive measures remain a cornerstone in the management of CHE across all etiological and morphological subtypes. The array of topical therapies for CHE is expanding with mounting evidence for newer agents that directly target the underlying pathophysiology of CHE compared to older agents that are more broadly anti-inflammatory. Phototherapy remains an effective option for CHE, but access and inconvenience remain barriers in many regions. Several advances in targeted systemic therapies for CHE have been made, with some agents approved for the treatment of moderate-to-severe atopic dermatitis exhibiting efficacy in hand and foot eczema, while other agents have evidence specifically for efficacy in CHE. With this evolving treatment landscape, an updated algorithm for the management of CHE is proposed.

Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by intense itch and eczematous skin lesions. Upadacitinib, a selective oral Janus kinase inhibitor, and dupilumab, a monoclonal antibody, are both approved treatments for moderate-to-severe AD. In period 1 of the LEVEL UP phase 3b/4 head-to-head study, upadacitinib-treated patients demonstrated higher simultaneous achievement of near complete skin clearance and little to no itch compared with dupilumab after 16 weeks of treatment in adults and adolescents with moderate-to-severe AD. The objective of period 2 of the LEVEL UP study was to assess the efficacy and safety of switching from dupilumab to upadacitinib in patients with inadequate response to dupilumab. Following period 1 of the LEVEL UP study, patients not achieving ≥ 75

The Psoriasis Epidemiology Screening Tool (PEST) is a 5-item questionnaire designed to identify patients with psoriasis who have co-existing psoriatic arthritis (PsA). This analysis investigated the longitudinal performance of the PEST questionnaire in the prospective, observational PURE registry. The PURE registry included 2132 patients with psoriasis who completed the PEST at baseline, 3 and 6 months then every 6 months for 5 years. Baseline diagnostic performance was assessed using existing PsA diagnoses as the reference standard. PEST positivity changes over time were assessed, and regression models determined factors linked to baseline PEST status and conversion from negative to positive. Cronbach’s alpha assessed internal consistency, while exploratory factor analysis evaluated changes in individual PEST questions over time. At baseline, 906 patients (42.5

INTRODUCTION:Hormonal therapies, typically used in the treatment of breast and prostate cancer patients, have been associated with numerous skin toxicities that can impact quality of life and interfere with treatment adherence. Appropriate management is necessary to improve the quality of life for cancer patients and survivors who experience hormonal therapy-related dermatologic toxicities.&nbsp;Objectives: To develop a practical, physician-developed algorithm for the management of hormonal therapy-related cutaneous adverse events using prescription treatment and non-prescription skincare. METHODS:The Nordic European Cutaneous Oncodermatology Management (NECOM) 6 advisory board integrated evidence from a structured literature search with the panel's expertise and clinical insights to create a practical algorithm for preventing and treating flushing/hot flashes, pruritus/urticaria, rosacea, alopecia, hirsutism, and hyperhidrosis associated with hormonal therapy.&nbsp;Results: An algorithm that aims to improve patient comfort during and after treatment, reduce the incidence of hormonal therapy-related cutaneous adverse events, and promote healing of affected skin areas by using prescription medication and skincare. Suggested management recommendations supplement the algorithm. CONCLUSIONS:Preventing and treating common dermatologic toxicities associated with hormonal cancer therapies is an essential component of care to improve patient quality of life, adherence to cancer treatment, and treatment outcomes. The NECOM 6 algorithm provides management strategies for all HCPs who treat oncology patients to prevent and treat common cutaneous adverse events associated with hormonal cancer therapies. J Drugs Dermatol. 2025;24:5(Suppl 1):s3-10.&nbsp.

BACKGROUND:Atopic dermatitis (AD) is a chronic inflammatory skin disease in which increased IL-22 expression contributes to epidermal hyperplasia and barrier defects. Temtokibart is a monoclonal antibody targeting IL-22RA1 (IL-22 receptor subunit alpha-1), blocking the signaling of IL-22 and potentially also of IL-20 and IL-24. OBJECTIVE:We evaluated the efficacy and safety of temtokibart in adults with moderate-to-severe AD. METHODS:In this phase 2a study (NCT04922021), 58 adults were randomized 1:1 to subcutaneous temtokibart 450 mg or placebo every 2 weeks for 16 weeks, with an additional dose (450 mg) at week 1, followed by additional 16 weeks of safety follow-up. The primary end point was change in Eczema Area Severity Index (EASI) from baseline to week 16. Biomarkers in serum, including IL-22, were analyzed as an exploratory end point. RESULTS:Mean change in EASI from baseline to week 16 was significantly greater for temtokibart compared to placebo (-15.3 vs -3.5; P = .003), corresponding to 65.4% and 19.7% improvement for temtokibart and placebo groups, respectively. At week 16, greater proportions of patients receiving temtokibart relative to placebo obtained EASI-75 (41.6% vs 13.7%; P = .011), EASI-90 (30.8% vs 3.5%; P = .003), and EASI-100 (20.9% vs 0%; P = .006). Treatment with temtokibart was well tolerated, and no safety signals were observed. Further, temtokibart treatment was associated with a general reduction of systemic inflammatory proteins. CONCLUSIONS:This proof-of-concept study demonstrates that targeting the IL-22 pathway with temtokibart is clinically effective with a favorable safety profile.

Vitiligo remains a highly burdensome disease associated with significant autoimmune and psychosocial comorbidities. Although the therapeutic landscape has long been dominated by off-label therapy, new treatments are emerging. Limited guidance on how to safely and effectively utilize available therapies poses challenges for healthcare providers. Herein, we provide generally accepted principles, consensus recommendations, and a treatment algorithm for the management of vitiligo, as developed by a panel of ten Canadian dermatologists with expertise in managing vitiligo. The three-phase process consisted of identifying themes and research questions; conducting a systematic literature review; and discussing/voting on generally accepted principles, consensus statements, and a treatment algorithm using an iterative consensus process. Experts agreed to 27 generally accepted principles, ten consensus statements, and a treatment algorithm. Education about vitiligo pathogenesis and repigmentation biology can help patients, caregivers, and healthcare providers set realistic expectations for treatment. Treatment should focus on repigmentation or stabilizing progression, rather than on depigmentation. Topical therapies include topical corticosteroids, topical calcineurin inhibitors, and the topical Janus kinase inhibitor ruxolitinib cream. Phototherapy, such as narrow-band ultraviolet B and excimer laser/lamp, can be used as monotherapy or in combination with other treatments. Off-label systemic therapies may be appropriate for patients with unstable or rapidly progressing disease. Surgical therapy may be suitable for patients with localized or stable recalcitrant disease. Maintenance therapy may help mitigate the risk of disease relapse. Improved clarity around the benefits, risks, and limitations of available therapies has supported the development of robust guidelines and a treatment algorithm for vitiligo. Disease stabilization and repigmentation are goals that can largely be achieved, particularly when patients share a mutual understanding of vitiligo and its treatment options. A Graphical Abstract is available for this article.

Importance Varying hair textures and hair care practices contribute to nuances in clinical presentation and management of scalp psoriasis across diverse patient populations. Cohort B of the VISIBLE trial enrolled participants with moderate to severe scalp psoriasis and skin of color, across the skin-tone spectrum. Objective To evaluate efficacy, quality of life, and adverse event outcomes of guselkumab, 100 mg, among participants with moderate to severe scalp psoriasis and skin of color over 48 weeks. Design, Setting, and Participants This ongoing phase 3b, randomized clinical trial at 45 sites in the US and Canada enrolled adults with skin of color and moderate to severe scalp psoriasis (scalp surface area [SSA] >= 30%; Psoriasis Scalp Severity Index [PSSI] >= 12; scalp-specific Investigator's Global Assessment [ss-IGA] score >= 3; >= 1 nonscalp plaque). Data were collected from September 2022 to June 2024. Interventions Randomized participants (3:1) received guselkumab, 100 mg, at weeks 0, 4, and every 8 weeks, or placebo at weeks 0, 4, and 12, then guselkumab at weeks 16, 20, and every 8 weeks. Main Outcomes and Measures Coprimary end points were ss-IGA score of 0 or 1 (ss-IGA 0/1) and 90% or greater improvement in PSSI (PSSI 90) at week 16 (guselkumab vs placebo). Major secondary end points included ss-IGA 0 (complete scalp clearance), PSSI 100, percentage changes from baseline in PSSI and SSA, changes from baseline in Dermatology Life Quality Index (DLQI) and Psoriasis Symptoms and Signs Diary (PSSD) symptoms score, and 4-point or greater reduction in Scalp Itch Numeric Rating Scale (NRS) score. Results Of 108 participants (81 randomized to guselkumab; 27 randomized to placebo), 100 (92.6%) completed 48 weeks of treatment. The mean (SD) age overall was 42.5 (13.6) years, and 58 participants (56.9%) were male. At the week 16 primary end point, in the guselkumab (n = 76) vs placebo (n = 26) groups, respectively, response rates were as follows: ss-IGA 0/1, 68.4% (n = 52) vs 11.5% (n = 3) (P < .001); PSSI 90, 65.8% (n = 50) vs 3.8% (n = 1) (P < .001); ss-IGA 0, 57.9% (n = 44) vs 3.8% (n = 1) (P < .001); PSSI 100, 59.2% (n = 45) vs 3.8% (n = 1) (P < .001); 4-point or greater reduction in Scalp Itch NRS score (in those with a baseline score of at least 4), 69.4% (n = 50 of 72) vs 24.0% (n = 6 of 25) (P < .001). Guselkumab efficacy increased and was maintained through week 48, when guselkumab-randomized participants achieved mean (SD) percentage improvements in PSSI and SSA of 94.6% (12.2%) and 94.8% (16.2%), respectively, and 51 (67.1%) achieved ss-IGA 0. DLQI and PSSD symptoms score least-squares mean changes were -9.7 (95% CI, -11.1 to -8.2) vs -2.2 (95% CI, -4.8 to 0.4) (P < .001) and -44.8 (95% CI, -50.6 to -39.1) vs -8.3 (95% CI, -18.4 to 1.9) (P < .001), respectively, with sustained improvements through week 48. Through week 16, infections were the most common adverse events in the guselkumab (n = 12; 14.8%) and placebo (n = 1; 3.7%) groups. Conclusions and Relevance In this randomized clinical trial, after 3 doses of guselkumab, most participants achieved significant scalp clearance and clinically meaningful quality-of-life improvements; improvements increased and were maintained through week 48. Trial Registration ClinicalTrials.gov Identifier: NCT05272150

As cancer prevalence continues to increase in Nordic countries, the amount of dermatological adverse events, termed cutaneous adverse events (cAEs), will also increase. The Nordic European Cutaneous Oncodermatology Management (NECOM) group aims to provide evidence-based guidance on how to treat and manage cAEs with an emphasis on supportive skincare regimens to improve patients'quality of life. The presented real-world cases demonstrate the use of the previous 6 NECOM recommendations in clinical practice. Experts in supportive oncodermatology share real patient cases and cAE treatment plans to serve as a guide for future healthcare providers. The cases highlight the use of daily skincare regimens containing gentle cleansers, moisturizers, and sunscreen that help to protect the skin from severe skin toxicities and help repair the skin barrier. Patients who were prescribed a daily skincare regimen consisting of Lipikar Syndet AP+ cleanser, Lipikar Baume AP+M, Cicaplast baume B5+, and Anthelios UVMUNE Do Not Copy SPF50+ sunscreen (La Roche-Posay) found that their cAEs were less severe and symptomatic. The products in the recommended skincare regimen Penalties Apply have all been tested for tolerance on patients undergoing cancer treatment. NECOM advisors emphasize the importance of selecting the right skincare products that will best nourish and heal sensitive skin and encourage patients and clinicians to encourage a proactive approach to skincare before, during, and after cancer-targeted therapies.

Background: There is limited evidence on treating psoriasis patients with skin of color (SOC), contributing to disparities in accessing appropriate care for these patients. Objectives: This study aimed to develop consensus statements defining SOC terminology and addressing needs to optimize the clinical management of psoriasis in patients with SOC. Methods: Using the modified Delphi methodology 16 Canadian dermatologists with expertise in psoriasis developed consensus statements. Four core faculty members drove the content of the study, and 12 additional panel members were consulted to vote and provide consensus on the content produced by the core faculty. At a final meeting, the full panel revised and voted on the final consensus statements. Results: The exercise resulted in 11 consensus statements on SOC terminology, as well as 5 primary and 4 secondary statements on clinical presentation and differential diagnosis, and treatment guidelines based on evidence and expert opinion. Four additional consensus statements on current assessment tools and access to care were developed based solely on expert opinion. Limitations: The available evidence was limited, low quality, and inappropriate for formal quality assessment. Conclusions: The consensus statements developed in this study may provide valuable guidance to the dermatology community treating psoriasis patients with SOC. ( JAAD Int 2025;19:12-20.)

BACKGROUND:Chronic hand eczema is a heterogeneous, fluctuating, and long-lasting disease affecting the hands and wrists that substantially affects quality of life. For severe chronic hand eczema, topical corticosteroids are often unsatisfactory and systemic treatment can be required. The aim of the head-to-head, phase 3 DELTA FORCE trial was to evaluate the efficacy and safety of topical delgocitinib cream versus oral alitretinoin, the only currently approved systemic drug for severe chronic hand eczema. METHODS:This randomised, assessor-masked, trial was conducted at 102 trial centres in Austria, Canada, France, Germany, Italy, Norway, Poland, Slovakia, Spain, and the UK. Adults (aged ≥18 years) with severe chronic hand eczema were randomly assigned (1:1) via an interactive response technology system to delgocitinib cream 20 mg/g (twice daily) or alitretinoin 30 mg (once daily) for up to 24 weeks. The primary endpoint was change in Hand Eczema Severity Index (HECSI) score from baseline to week 12. Efficacy of delgocitinib cream versus alitretinoin was assessed in all eligible randomly assigned patients who had available data at baseline, and safety was assessed in all patients exposed to trial treatment. The trial is registered with ClinicalTrials.gov (NCT05259722) and is complete. FINDINGS:Between June 15, 2022, and Dec 5, 2023, 513 (334 [65%] female and 179 [35%] male) patients were randomly assigned to receive delgocitinib cream (n=254) or alitretinoin (n=259). Ten patients were excluded after randomisation due to not meeting eligibility criteria, so the full analysis set consisted of 250 patients in the delgocitinib group and 253 in the alitretinoin group. One patient in the delgocitinib group and three in the alitretinoin group were excluded from the primary analysis as they had missing HECSI data at baseline. A significantly greater least squares mean change in HECSI score from baseline to week 12 was observed with delgocitinib cream (-67·6 [SE 3·4]; n=249) versus alitretinoin (-51·5 [3·4]; n=250; difference -16·1 [95% CI -23·3 to -8·9], p<0·0001). Fewer patients reported adverse events in the delgocitinib group (125 [49%] of 253 patients) than in the alitretinoin group (188 [76%] of 247). The most frequent adverse events were headache (ten [4%] in the delgocitinib group vs 80 [32%] in the alitretinoin group), nasopharyngitis (30 [12%] vs 34 [14%]), and nausea (one [<1%] vs 14 [6%]). INTERPRETATION:Delgocitinib cream showed superior efficacy and a more favourable safety profile versus oral alitretinoin over 24 weeks. These results support the benefit of delgocitinib cream in patients with severe chronic hand eczema. FUNDING:LEO Pharma.

Background: Amlitelimab, a fully human nondepleting mAb targeting OX40 ligand on antigen-presenting cells, could prevent T-cell-driven inflammation seen in atopic dermatitis (AD). Objective: This trial evaluated the efficacy and safety of amlitelimab in adults with AD. Methods: In this 2-part, phase 2b, randomized, double-blinded placebo-controlled trial (ClinicalTrials.gov identifier NCT05131477), patients received subcutaneous amlitelimab every 4 weeks at doses of 250 mg plus a 500-mg loading dose, 250 mg, 125 mg, or 62.5 mg or placebo for 24 weeks in Part 1 (1:1:1:1:1 randomization). In Part 2, clinical responders were reallocated 3:1 to stop taking amlitelimab or continue the previous dose regimen for 28 weeks. The primary end point was percentage of change in Eczema Area and Severity Index (EASI) from baseline to week 16. Results: In all, 390 and 190 patients enrolled in Part 1 and Part 2, respectively. A significant percentage of change decrease in EASI was observed with amlitelimab doses versus with placebo (P < .001). Clinical responses at week 24 (Investigator Global Assessment 0/1 and/or a 75% reduction in EASI) were maintained at week 52 in patients continuing or stopping amlitelimab. Of the patients maintaining clinical response at week 52 after no longer receiving treatment, more than 80% had serum amlitelimab concentrations less than the 4-mu g/mL threshold for several weeks before week 52. Reductions in AD-related biomarkers during Part 1 were maintained through Part 2. Amlitelimab was well tolerated over 52 weeks. Conclusions: Amlitelimab treatment significantly reduced clinical and biomarker responses, and was well tolerated in adults with AD through week 52. Sustained responses were observed in the majority of patients for 28 weeks after they had stopped taking amlitelimab.