Lebrikizumab is effective in Patients with Atopic Hand and Foot Dermatitis: 16-Week Results from the Randomized, Double-Blind, Placebo-Controlled ADtouch Trial

Background : Atopic hand and foot dermatitis (AHFD) is a common, recalcitrant, and debilitating manifestation of atopic dermatitis (AD) driven by type 2 inflammation, including overexpression of interleukin-13, with pruritus and pain as primary symptoms. Despite substantial impact on quality of life (QoL) and work productivity, systemic treatment options for AHFD remain limited. Objectives : To evaluate efficacy and safety of lebrikizumab, a selective interleukin-13-inhibitor, as monotherapy in adults and adolescents with moderate-to-severe AHFD. Methods: ADtouch (NCT06921759) was a multi-center, randomized, double-blind, placebo-controlled, parallel-group phase 3b trial evaluating lebrikizumab versus placebo in adults (≥18 years) and adolescents (≥12 to <18 years, ≥40kg total body weight) with moderate-to-severe AHFD. Eligible patients had AHFD ≥1 year in at least 2 of 4 anatomical areas (left hand/right hand/left foot/right foot) at screening and baseline; a documented history of AD not limited to hands and feet; a Hand Foot Investigator’s Global Assessment (HF-IGA) score of moderate (3) or severe (4) at screening and baseline; a HF-Peak Pruritus Numeric Rating Scale (NRS) score ≥4; and inadequate response to topical therapies. Patients were randomized 1:1 to subcutaneous lebrikizumab (500mg loading doses at baseline and week 2, then 250mg every 2 weeks to week 16) or placebo. The primary endpoint was HF-IGA 0/1 with ≥2-point improvement from baseline at week 16. Secondary endpoints evaluated safety, pruritus, pain, disease activity, QoL, and Atopic Hand Dermatitis Clearance Satisfaction (AHDCS), a novel single-item patient-reported scale. Results reflect the primary outcome database lock, which included all data through Week 16. Results: Participants (N=221) were randomized to lebrikizumab (n=110) or placebo (n=111). Baseline disease characteristics were comparable between groups, including HF-IGA (severe: 27.3% vs 27.9%), HF-Peak Pruritus NRS (mean: 7.2 in each arm) and HF-Peak Pain NRS (mean: 6.2 in each arm). All primary and key secondary endpoints achieved statistical significance. More participants in the lebrikizumab group achieved HF-IGA 0/1 with ≥2-point improvement vs placebo at week 16 (53.3% vs. 27.2%; p<0.001). A higher proportion of lebrikizumab vs placebo-treated participants achieved HF-IGA 0/1 with ≥2-point improvement at week 2 (7.8% vs 0.9%; nominal p<0.05) and week 4 (16.9% vs 5.6%; p=0.008). At weeks 2, 4, and 16, HF-Peak Pruritus NRS ≥4-point improvements were higher with lebrikizumab (15.8%; 27.3%; 57.1%) than with placebo (0.9%; 7.9%; 19.0%; all p<0.001). HF-Peak Pain NRS ≥4-point improvements were higher for lebrikizumab vs placebo at week 16 (59.1% vs 18.8%; p<0.001). Among participants who were not satisfied at baseline on AHDCS, more lebrikizumab than placebo-treated participants were "satisfied" or "very satisfied" with hand dermatitis clearance at week 16 (76.7% vs 39.6%; p<0.001). Treatment-emergent adverse events (TEAEs) were reported in 41.8% of patients receiving lebrikizumab and 39.6% of patients receiving placebo; no severe TEAEs and no serious AEs were reported, and treatment discontinuations due to AEs were infrequent in lebrikizumab (0.9%) and placebo groups (2.7%). Conclusion: Lebrikizumab monotherapy achieved clinically meaningful and statistically significant improvements over placebo in atopic hand and foot dermatitis skin clearance, pruritus, pain, and patient satisfaction. Safety findings were consistent with the established lebrikizumab profile.