The ALLEGRO phase 2a and 2b/3 studies demonstrated that ritlecitinib, an oral JAK3/TEC family kinase inhibitor, is efficacious at doses of ≥ 30 mg in patients aged ≥ 12 years with alopecia areata (AA). The objective of this study was to evaluate the safety of ritlecitinib in an integrated analysis of four studies in AA. Two cohorts were analyzed: a placebo-controlled and an all-exposure cohort. Proportions and study size–adjusted incidence rates (IRs) of adverse events (AEs) of interest and laboratory abnormalities are reported. In the placebo-controlled cohort (n = 881; median exposure: 169 days), the proportion of ritlecitinib-treated patients with AEs was 70.2–75.4

We report efficacy and safety of lebrikizumab up to 152 weeks (W) of continuous treatment with/without topical corticosteroids in the ADjoin long-term extension study. ADvocate1 2 W16 lebrikizumab responders (Eczema Area and Severity Index (EASI) 75 or Investigator’s Global Assessment (IGA) 0/1 without rescue) were re-randomized 2:2:1 lebrikizumab (LEB) 250 mg Q2W, Q4W, or placebo (lebrikizumab withdrawal, not presented herein) to the 36W maintenance period before entering ADjoin. ADhere W16 lebrikizumab responders were re-randomized 2:1 LEBQ2W/Q4W upon entering ADjoin. Data are reported as observed for W16 lebrikizumab responders from ADvocate1 2 (N = 181) and ADhere (N = 86) who received treatment up to ADjoin W100 (152W/116W for ADvocate1 2/ADhere). The Supplement reports additional populations. In participants who achieved IGA 0/1 at W16, 84.0

BACKGROUND:The results of a previous phase IIa trial suggested efficacy of the anti-C5a compound vilobelimab in a small number of patients with severe hidradenitis suppurativa (HS) refractory to adalimumab treatment. OBJECTIVES:To study the efficacy of vilobelimab in a larger-scale randomized phase IIb trial (SHINE) of patients with moderate-to-severe HS. METHODS:In total, 177 patients with moderate-to-severe HS were treated either with placebo or one of four doses of vilobelimab, a monoclonal antibody that targets the complement split product C5a. Hidradenitis Suppurativa Clinical Response (HiSCR) at 16 weeks was the primary endpoint. Those who achieved HiSCR switched to open-label low-dose vilobelimab; those who did not were switched to medium-dose vilobelimab. The trial was registered with the EU Clinical Trials Register (EudraCT number 2017-004501-40) and ClinicalTrials.gov (NCT03487276). RESULTS:The study did not meet the primary endpoint, perhaps due, in part, to an unexpectedly high HiSCR placebo response rate of 47.1%. HS flares decreased and post hoc analysis showed that high-dose vilobelimab significantly decreased the median draining tunnel counts and IHS4 score by 63%. Following the switch to medium-dose vilobelimab at week 16, 45.5% of those who did not respond to treatment achieved HiSCR at week 40. CONCLUSIONS:Compared with placebo, vilobelimab treatment did not result in significant HiSCR improvements in patients with moderate-to-severe HS. Post hoc analysis revealed significant effects for the highest tested dose on draining tunnel reduction and IHS4 score, which captures reductions in draining tunnels. These findings warrant further investigation.

Background Achievement of full scalp hair regrowth is an important outcome for patients with severe AA. Baricitinib is a selective JAK inhibitor that is approved in adults to treat severe AA and has now been studied in 257 adolescents (ages 12 to <18 years). In both populations, significant scalp hair regrowth (SALT score <20) was achieved in clinical trials. This analysis evaluates complete response thresholds of SALT score <10 and <5 among SALT score <20 responders, through Weeks (Wk) 36 and 52 in adolescent and adult populations, respectively. Methods Among BRAVE-AA1/2 (NCT03570749, NCT03899259) and BRAVE-AA-PEDS (NCT05723198) trials, baricitinib 4mg and 2mg responders (SALT score ≤20) were evaluated for achievement of SALT score ≤10 or ≤5 at Wk4, 8, 12, 16, 24, 36, and 52*. Results Among those patients treated with baricitinib 4mg, the proportion of adult responders who achieved SALT score <10 at Wk36 and Wk52 was 74.6% (150/201) and 75.0% (171/228); and the proportion in adolescents at Wk36 was 86.1% (31/36). Among those patients treated with baricitinib 4mg, the proportion of adults who achieved SALT score <5 at Wk36 and Wk52 was 55.2% (111/201) and 62.7% (143/228); and the proportion in adolescents at Wk36 was 61.1% (22/36). Some patients achieved these responses as early as Wk8 in both adult and adolescent populations.Among those patients treated with baricitinib 2mg, the proportion of adults who achieved SALT score <10 at W36 and W52 was 62.2% (51/82) and 71.0% (66/93); and the proportion in adolescents at W36 was 78.3% (18/23). Among those patients treated with baricitinib 2mg, the proportion of adults who achieved a SALT score <5 at W36 and W52 was 42.7% (35/82) and 47.3% (44/93); and the proportion in adolescents at W36 was 60.9% (14/23). Some patients achieved these responses as early as W8 in both adult and adolescent populations. Conclusion Baricitinib treated adult and adolescent patients who were responders (SALT score ≤20) had increasing depth of response over time with continued therapy, and the majority achieved full scalp hair regrowth. Footnote *Week 52 data is not yet available for the BRAVE-AA-PEDS trial.

Background:Atopic dermatitis is a chronic, relapsing, and remitting inflammatory skin disease. Multiple systemic therapeutic options are available to treat atopic dermatitis. Objective:To provide evidence-based recommendations on the use of systemic therapies for atopic dermatitis in Canada that consider the nuances of the Canadian healthcare system and provide guidance for populations of clinical interest. Methods:A panel of 14 experts, including 11 dermatologists from Canada and 3 from the United States, reviewed available literature on systemic therapies for atopic dermatitis. The published evidence, along with clinical expertise and opinion, was used to draft a concise set of statements to guide healthcare providers in Canada on systemic treatment of atopic dermatitis. Results:During 3 rounds of virtual meetings with all 14 experts voting in all meetings, a total of 29 statements reached the 75% agreement required for consensus. Limitations:The consensus statements are based on expert opinions and consensus in the absence of evidence-based clinical research for patient outcomes. The statements represent considerations for patient management and not specific guidelines for patient treatment. Conclusion:The recommendations and statements provided serve to guide Canadian healthcare providers on the practical aspects of managing systemic-eligible patients with atopic dermatitis.

Background Overexpression of interleukin (IL)-17A and IL-17F significantly influences psoriasis pathology. Until recently, biologics targeting IL-17A alone, like secukinumab, were used to treat psoriasis. Bimekizumab is a monoclonal IgG1 antibody that targets both IL-17A and IL-17F. BE RADIANT was the first phase 3 study to investigate switching from selective inhibition of IL-17A to dual inhibition of IL-17A and IL-17F. Bimekizumab has previously shown superior achievement of complete skin clearance (PASI 100) versus secukinumab through 48 weeks. Switching from secukinumab to bimekizumab resulted in improved clinical responses. Over 2 years, no new safety signals were observed. Objective To report 3-year efficacy and safety of bimekizumab in patients with moderate to severe plaque psoriasis receiving continuous bimekizumab, or switching from secukinumab after 1 year. Methods The BE RADIANT phase 3b randomised controlled trial had a 48-week double-blinded period, in which patients received bimekizumab (320 mg every 4 weeks [Q4W]), or secukinumab (300 mg weekly to Week 4, then Q4W). At Week 16, bimekizumab-randomised patients underwent re-randomisation to receive Q4W or Q8W maintenance dosing. From Week 48 onwards (open-label extension), all received bimekizumab. Results 336 bimekizumab- and 318 baseline secukinumab-randomised patients entered the open-label extension. Among these, more bimekizumab-randomised patients achieved PASI 100 (modified non-responder imputation) at Year 1 (74.9%) versus secukinumab-randomised patients (52.8%). PASI 100 response rates were maintained over 3 years in bimekizumab-treated patients (68.8%) and increased in secukinumab-randomised patients switching to bimekizumab (68.8%). Bimekizumab was well-tolerated to 3 years. In patients receiving ≥1 bimekizumab dose, the most common treatment-emergent adverse events (TEAEs) over 3 years were nasopharyngitis, oral candidiasis, and upper respiratory tract infection (exposure adjusted incidence rates: 12.2, 10.0, and 5.5/100 patient-years, respectively). Rates of TEAEs of interest, including serious infections, inflammatory bowel disease, and suicidal ideation and behaviour, did not increase with longer exposure to bimekizumab from 1 to 3 years. Conclusion Over two-thirds of bimekizumab-randomised patients and those switching from secukinumab to bimekizumab achieved and maintained complete skin clearance over 3 years of treatment. Over 3 years, bimekizumab was well-tolerated, and TEAE rates did not increase with longer exposure.

BACKGROUND:Delgocitinib cream is the only topical treatment that has been specifically developed and approved for moderate to severe Chronic Hand Eczema (CHE). OBJECTIVE:The objective of this trial was to evaluate the long-term safety and efficacy of delgocitinib cream 20 mg/g as needed for 36 weeks in adults with CHE. METHODS:In phase 3 open-label DELTA 3 (NCT04949841), patients who completed the 16-week treatment period in the DELTA 1 and 2 trials were treated on an as-needed basis with twice-daily delgocitinib cream for 36 weeks (n= 801). Patients with Investigator's Global Assessment for CHE (IGA-CHE) ≥2 received treatment until IGA-CHE ≤1 was achieved. The primary endpoint was the number of treatment-emergent adverse events. Key secondary endpoints were IGA-CHE 0/1 and ≥75%/≥90% improvement in Hand Eczema Severity Index (HECSI-75/90) scores. RESULTS:Delgocitinib was well-tolerated (n= 801; R = 231.1; patient years of observation = 535.7), with most frequent adverse events being COVID-19 and nasopharyngitis. DELTA 3 baseline IGA-CHE 0/1 (24.6%) and HECSI-75/HECSI-90 (51.8%/31.8%) were maintained to week 36 (30.0% and 58.6%/36.6%, respectively) among delgocitinib-treated patients in the parent trials. Among those previously treated with cream vehicle, corresponding response rates improved from DELTA 3 baseline (9.1% and 23.7%/12.0%, respectively) to week 36 (29.5% and 51.5%/35.7%). LIMITATIONS:Open-label trial. CONCLUSION:Delgocitinib cream treatment was well-tolerated and efficacious in maintaining disease control in patients with CHE for up to 52 weeks.

Introduction: Abrocitinib, an oral, once-daily, JAK1-selective inhibitor, is approved in patients aged ≥12 years at the recommended doses of 100 mg and 200 mg for the treatment of moderate-to-severe atopic dermatitis (AD). JADE REAL (NCT04564755) was a global, open-label expanded access protocol initiated in 2020 (completed September 2024) to provide access to abrocitinib for patients with moderate-to-severe AD. This analysis evaluated dosing patterns and incidence of treatment-emergent adverse events (TEAEs) leading to a change in dose of abrocitinib inpatients with moderate-to-severe AD in an expanded access protocol simulating real-world use of abrocitinib. Procedure/Study: Eligible patients aged ≥12 years with moderate-to-severe AD initiated once-daily abrocitinib 100 mg or 200 mg (plus topical medication as needed). The dose could be changed throughout the treatment period. Initial dosing and the proportion of patients with continuous dosing, ≥1 dose change and >1 dose change were assessed. Safety was assessed via TEAE monitoring. Results: Of 312 patients, 120 (38.5%) and 192 (61.5%) patients initiated abrocitinib 100 mg and 200 mg, respectively (mean [SD] treatment duration: 379.1 days [203.3]). More patients of ages ≥12–18 and ≥65 years, Black/African American race, and with moderate AD initiated abrocitinib 100 mg, while more patients of ages ≥18–<65 years, Asian race, and with severe AD initiated abrocitinib 200 mg. Of patients who initiated abrocitinib 100 mg and 200 mg, 78 (65.0%) and 119 (62.0%) received continuous dosing, and 42 (35.0%) and 73 (38.0%) patients had ≥1 dose change, including 12 (28.6%) and 33 (45.2%) patients with >1 dose change, respectively. TEAEs led to dose reduction in 27 patients (8.7%), notably nausea (n=4 [1.3%]), thrombocytopenia (n=4 [1.3%]), acne (n=3 [1.0%]), fatigue (n=3 [1.0%]), and folliculitis (n=3 [1.0%]). TEAEs led to a dose escalation in 12 patients (3.8%); AD was the only TEAE that occurred in ≥1% of patients (n=10 [3.2%]) which led to a dose escalation. Conclusion: Most patients received consistent abrocitinib dosing throughout the study. TEAEs were not the primary reason leading to dosage reduction. These results may support clinical decision making around initial dose selection and dosage changes. JADE REAL demonstrated the potential benefits of flexible dosing and may simulate the real-world use of oral Janus kinase inhibitors. Funding/Disclosures: This study was funded by Pfizer.

Introduction Abrocitinib, an oral Janus kinase (JAK) 1-selective inhibitor, is approved to treat moderate-to-severe atopic dermatitis (AD) in patients aged ≥12 years. Many patients initiating abrocitinib in the real world have received prior biologic therapy but are under-represented in clinical trials. The primary objective of JADE REAL (NCT04564755), a global, open-label, expanded access protocol study, was to provide early access to abrocitinib for patients for whom available and approved medications for AD were inadequate. This post-hoc analysis of JADE REAL examined treatment patterns and exploratory efficacy outcomes by prior biologic exposure. Methods Patients initiated daily abrocitinib 100 or 200 mg, per investigator discretion, with dose switching allowed to simulate the real-world use of JAK inhibitors. Baseline patient characteristics, prior biologic use (exposed and naive), and use of concomitant rescue medications were collected. Treatment patterns and Eczema Area and Severity Index (EASI) total score, percentage body surface area (%BSA) involvement, Peak Pruritus Numerical Rating Scale (PP-NRS), and Patient-Oriented Eczema Measure (POEM) at Week 72 were described. Results Overall, 89 biologic-exposed and 223 biologic-naive patients were included. Demographic and disease characteristics were similar between groups. A higher proportion of exposed patients initially received abrocitinib 200 mg (61 [68.5%]) than naive patients (131 [58.7%]) and had ≥1 dose change in both initial dose groups (initial dose 100 mg, 15 [53.6%]; 200 mg, 27 [44.3%]) than naive patients (100 mg, 27 [29.3%]; 200 mg, 46 [35.1%]). Median (IQR) abrocitinib treatment duration was similar among exposed and naive patients (351.0 [259.0-500.0] & 378.0 [246.0-510.0] days). Exposed and naive patients demonstrated improvements in the mean (SD) from baseline to Week 72 for EASI total score (20.1 [12.3]-3.0 [6.6] & 23.3 [12.8]-3.9 [7.8]), %BSA involvement (32.5 [21.4]-4.6 [9.5] & 35.1 [21.4]-8.2 [16.0]), PP-NRS (7.2 [2.2]-1.6 [1.6] & 7.5 [2.0]-2.4 [2.4]) and POEM (19.7 [5.7]-4.3 [4.0] & 20.2 [5.6]-7.0 [7.7]). Few exposed and naive patients required concomitant rescue treatments (6 [6.7%]; 10 [4.5%]). Conclusions Biologic-exposed and -naive patients with moderate-to-severe AD receiving abrocitinib in JADE REAL experienced improvements in EASI total score, %BSA involvement, PP-NRS, and POEM; few required concomitant rescue medications. Abrocitinib flexible dosing enables optimized treatment for biologic-naive patients and biologic-exposed patients, which are a difficult-to-treat population. Funding This study was funded by Pfizer.

Seborrheic dermatitis is a chronic inflammatory skin condition characterized by erythematous patches and plaques with white-to-yellow greasy scale often localized to the scalp and face. Its presentation varies between children and adults, as well as across different skin tones. Notably, in patients with more richly pigmented skin, postinflammatory pigment alteration can also be a feature of seborrheic dermatitis, highlighting the importance of considering skin colour differences in the diagnosis. Clinical manifestations of seborrheic dermatitis can overlap with several other dermatoses, including atopic dermatitis, psoriasis, and rosacea, thereby necessitating careful evaluation for accurate diagnosis. The pathophysiology of seborrheic dermatitis involves a complex interplay between dermatological, neurological, immunological, and microbiome-related factors. The multifaceted nature of seborrheic dermatitis underscores the need for a comprehensive approach to its diagnosis, considering age, skin colour, cultural practices, and comorbidities. This is the second in a series of 3 reviews, each addressing different aspects of seborrheic dermatitis, including its epidemiology, diagnosis, and treatment considerations.

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.

BACKGROUND:Psoriatic disease is a lifelong chronic illness for which there is no cure. It is well established that psoriasis leads to a major impairment of health-related quality-of-life and wellbeing. Most people with psoriasis live together with partners, bringing along a major burden for them. The FamilyPso was created to measure this burden in psoriasis. OBJECTIVE:The aim of the FamilyPso international study was to validate this tool and to show feasibility for the use of the FamilyPso across multiple countries. METHODS:A prospective cohort study was conducted in 11 centers in Austria, Canada, Germany, Italy, Spain, and Turkey. The factor structure of the FamiliyPso was examined by confirmatory factor analysis (CFA) including tests of measurement invariance for gender and language. Subgroups (e.g., countries and gender) were tested for significant differences, and the relationship between the severity of illness and FamilyPso scores was tested for differences between countries using a mixed regression model. Descriptive statistics for items and scores are presented herein. RESULTS:The cohort consisted of 556 people with psoriasis and their partners. Patients agreed that their partners would answer the questionnaire in their absence and return the forms to the centers. The mean age of patients and partners was 51 years. Psoriasis severity was mild in 57.6%, moderate in 31.5%, and severe in 10.9% of cases, and 91.3% received treatment. The results of the CFA confirmed the original factor structure with minor modifications. Self-assessed high severity of psoriasis was a predictor for a higher burden in 4/5 FamilyPso domains. There was an increased burden to partners related to the severity of psoriasis particularly in the domain "general emotional strain," including items such as a "feeling of helplessness." The results of the study showed that the FamilyPso could assess the burden of partners of people with psoriasis and can be used across different countries. CONCLUSIONS:The data can improve management of psoriatic disease and should be considered in shared decision-making.