British Journal of Dermatology最新文献

Background: Moderate-to-severe atopic dermatitis (AD) impacts patients' quality of life (QOL). More treatment options are urgently needed to manage this chronic disease. Lebrikizumab is a monoclonal antibody that binds to IL-13, a key mediator in AD pathogenesis. In Japanese patients, lebrikizumab has been evaluated through week (W) 16 in the randomized, placebo-controlled, phase III ADhere-J study.

Objectives: To evaluate long-term efficacy and safety of lebrikizumab in combination with topical corticosteroids (TCS) in the ADhere-J study.

Methods: Patients aged ≥12 years and weighing ≥40 kg with moderate-to-severe AD, and receiving either subcutaneous lebrikizumab 250 mg every 2 weeks (Q2W)/every 4 weeks (Q4W) or placebo during the 16-week induction period, were evaluated during the long-term maintenance period from W16 to W68. Responders achieved co-primary endpoints at W16: Investigator's Global Assessment score of 0 or 1 (IGA [0,1]) with ≥2-point improvement from baseline, and/or ≥75% improvement from baseline in Eczema Area and Severity Index (EASI 75). In this analysis, W16 responders received lebrikizumab 250 mg Q2W or Q4W combined with TCS during the maintenance period (maintenance primary population; MPP); W16 per-protocol nonresponders received lebrikizumab Q2W with TCS (maintenance escape population; MEP). Major endpoints included IGA (0,1) with ≥2-point improvement from baseline and EASI 75 through W68. Other outcomes included QOL, itch, and serum thymus and activation-regulated chemokine.

Results: At W68, 66-81% of 103 patients in the MPP and 32-38% of 168 patients in the MEP achieved IGA (0,1) with ≥2-point improvement from baseline. EASI 75 was maintained by 83-89% of patients in the MPP, while 71-80% of patients in the MEP achieved this outcome by W68. Across treatment arms, patients in the MPP tended to maintain improvements recorded at W16, while patients in the MEP steadily improved across the maintenance period. No new safety signals were reported, and most treatment-emergent adverse events were mild or moderate in severity in both populations. Safety outcomes were consistent with previous reports for lebrikizumab treatment in global studies.

Conclusions: These results support the use of lebrikizumab in combination with TCS for moderate-to-severe AD in the Japanese population over the long term.

Clinical trial registration: ClinicalTrials.gov (NCT04760314).

Background: Deucravacitinib, an oral, selective, allosteric tyrosine kinase 2 inhibitor, is approved in the United States, European Union, Japan, South Korea, China, and other countries for treatment of moderate-to-severe plaque psoriasis.

Objective: To evaluate the efficacy and safety of deucravacitinib in Asian patients with moderate to severe plaque psoriasis.

Methods: In the 52-week, blinded, phase 3 POETYK PSO-3 trial (NCT04167462), patients were randomized 1 : 2 to placebo (n = 74) or deucravacitinib 6 mg once daily (n = 146) for 16 weeks followed by deucravacitinib alone. Coprimary endpoints were achievement of ≥ 75% reduction from baseline in Psoriasis Area and Severity Index (PASI 75) and static Physician Global Assessment score of 0 (clear) or 1 (almost clear) (sPGA 0/1) at Week 16. Efficacy and safety were evaluated throughout.

Results: At Week 16, significantly higher proportions of patients receiving deucravacitinib versus placebo achieved PASI 75 (68.8% vs. 8.1%; P < 0.0001) and sPGA 0/1 (55.6% vs. 6.8%; P < 0.0001). Response rates with deucravacitinib were maintained through Week 52. Common adverse events included upper respiratory tract infection and nasopharyngitis. Serious adverse event and discontinuation rates were low.

Conclusions: Deucravacitinib was efficacious and well tolerated in Asian patients with moderate to severe plaque psoriasis.

Background: The effects of childhood obesity or weight gain on the development of early-onset follicular occlusion triad (FOT) among children, which includes hidradenitis suppurativa (HS), acne conglobata (AC), and dissecting cellulitis of the scalp (DCS), remain unknown.

Objectives: To investigate the association between body mass index (BMI) or its changes and early-onset FOT development.

Methods: This nationwide population-based longitudinal cohort study included a cohort of 2,012,928 Korean children who underwent two consecutive health examinations at 30-36 months and 42-48 months of age between 2009 and 2020. The BMI and its changes derived during health screenings at 30-36 and 42-48 months. We performed multivariate Cox proportional hazards regression analyses to estimate the risk of early-onset FOT, including HS, AC, and DCS.

Results: During the follow-up, 1,283 FOT, including 143 HS, 1,068 AC, and 72 DCS, events were identified. Children with obesity were at an elevated risk of early-onset FOT compared to those with a normal weight (FOT: adjusted hazard ratio [aHR] 1.49, 95% confidence interval [CI] 1.21-1.84; HS: aHR 2.30, 95% CI 1.39-3.82; AC: aHR 1.36, 95% CI 1.07-1.73). BMI gain was correlated with an elevated risk of early-onset FOT, particularly HS, whereas BMI loss was linked to a decreased risk of early-onset FOT, especially HS. Children who became obese had an increased early-onset FOT risk (aHR 1.51, 95% CI 1.07-2.14) compared to those who maintained a normal weight. Children who reduced from obese to normal weight exhibited a decreased risk of early-onset FOT (FOT: aHR 0.41, 95% CI 0.17-0.96, P for trend=0.02; HS: P for trend=0.05) compared to obese children who retained their weight.

Conclusions: Childhood obesity was associated with an elevated risk of early-onset FOT, including HS and AC. Weight gain was correlated with an increased risk of early-onset FOT, especially HS, while weight loss was associated with a decreased risk of early-onset FOT, particularly HS. Implementing purposeful weight-reduction strategies may be helpful in preventing early-onset FOT development.

Background: The ALLEGRO phase 2a and 2b/3 studies demonstrated that ritlecitinib is efficacious and well tolerated in adult and adolescent patients with alopecia areata (AA) up to 48 weeks.

Objective: The efficacy of ritlecitinib through Month 24 and safety through data cutoff were assessed in the ALLEGRO phase 2b/3 study and the ongoing long-term, open-label, phase 3 ALLEGRO-LT study.

Methods: Patients aged ≥12 years with AA and ≥50% scalp hair loss from ALLEGRO-2b/3 who rolled over to ALLEGRO-LT after up to 48 weeks were included. Proportions of patients with responses based on clinician-reported Severity of Alopecia Tool (SALT) score of ≤20 and ≤10, eyebrow assessment (EBA) and eyelash assessment (ELA), patient global impression of change (PGI-C) and patient satisfaction with hair growth are reported through Month 24 for patients who received ritlecitinib 50 mg daily with or without a 200-mg 4-week daily loading dose. Observed and imputed data (last observation carried forward [LOCF]) were reported until December 9, 2022. Safety was assessed throughout.

Results: At Month 12, SALT score ≤20 was achieved by 45.1% and 45.9% (observed) and 40.3% and 41.8% (LOCF) of the 191 and 194 patients who received ritlecitinib 50 mg and ritlecitinib 200/50 mg, respectively. At Month 24, proportions increased to 60.8% and 63.1% (observed) and 46.1% and 50.8% (LOCF), respectively. Patients with abnormal EBA or ELA scores at baseline achieved responses at Month 24 (EBA observed: 57.6% [50 mg], 61.0% [200/50 mg]; EBA LOCF: 46.8% [50 mg], 50.9% [200/50 mg]; ELA observed: 51.2% [50 mg], 62.7% [200/50 mg]; ELA LOCF: 43.2% [50 mg], 51.7% [200/50 mg]). PGI-C response was achieved by patients at Month 24 (observed: 70.0% [50 mg], 76.4% [200/50 mg]; LOCF: 56.6% [50 mg], 65.5% [200/50 mg]). Safety profiles for both treatment groups were consistent with the known safety profile of ritlecitinib.

Conclusion: Ritlecitinib has clinically meaningful and sustained efficacy beyond 1 year with a favourable safety and tolerability profile, supporting its long-term use in patients aged ≥12 years with AA.

Trial registries: ClinicalTrials.gov: NCT03732807, NCT04006457.