Tralokinumab monotherapy improves atopic dermatitis severity in patients with moderate-to-severe atopic hand eczema

Introduction: Atopic dermatitis (AD) is a chronic inflammatory skin disease that commonly affects multiple body regions, with involvement of the head, neck, and hands often being particularly burdensome. ADHAND was the first phase 3 trial to evaluate targeted IL-13 inhibition in patients with AD and moderate-to-severe hand involvement. At Week 16, tralokinumab monotherapy significantly improved AD hand-specific signs and symptoms, and quality of life. Patients in ADHAND were required to have AD affecting at least one body area beyond the hands. Here, we assess the efficacy of tralokinumab monotherapy versus placebo on overall AD severity beyond the hands in the ADHAND study population. Methods: ADHAND (NCT05958407) was a phase 3b, randomized, controlled, double-blind trial. Participants were randomized 2:1 to receive tralokinumab monotherapy 300 mg or placebo, every two weeks, for 16 weeks. Predefined exploratory outcomes included the proportion of patients achieving ≥75% or ≥90% reduction from baseline to Week 16 in Eczema Area and Severity Index (EASI-75/90). Predefined subgroup analyses were based on baseline disease severity: EASI≤7 (mild), EASI>7 (moderate-to-severe), and EASI≥16 (inclusion criterion used in the tralokinumab pivotal trials). Statistical analyses followed pre-specifications; data after rescue treatment, discontinuation due to adverse events, or discontinuation due to lack of efficacy were imputed as non-response, while other missing data were handled using multiple imputation. Results: Baseline mean (±SD) EASI was similar in the tralokinumab monotherapy group (N=156; 9.18±9.10) and placebo group (N=78; 9.33±8.83). Of the 234 patients included in the analysis, 136 had baseline EASI≤7 (tralokinumab n=92; placebo n=44), 98 had EASI>7 (tralokinumab n=64; placebo n=34), and 36 had EASI≥16 (tralokinumab n=24; placebo n=12). At Week 16, a higher proportion of all patients receiving tralokinumab monotherapy achieved EASI-75 (47.6% vs 19.8%) and EASI-90 (27.9% vs 9.5%) versus placebo (both P<0.001). Across baseline severity subgroups, results consistently favored tralokinumab. In patients with baseline EASI≤7, EASI-75 and EASI-90 were achieved by 39.9% versus 10.8% (P<0.001) and 28.8% versus 5.9% (P<0.001), respectively. In patients with baseline EASI>7, corresponding response rates were 58.4% versus 30.4% (P<0.01) and 26.5% versus 13.1% (P=0.103). In the subgroup with baseline EASI≥16, EASI-75 and EASI-90 were achieved by 43.1% versus 9.0% (P<0.01) and 30.3% versus 0% (P<0.01). Conclusion: In patients with AD and moderate-to-severe hand involvement, tralokinumab monotherapy significantly reduced overall AD outcomes beyond the hands, with higher EASI-75 and EASI-90 response rates compared with placebo at Week 16. Treatment effects were broadly consistent across baseline disease-severity subgroups, including marked differences in patients with baseline EASI≥16. Response rates observed in ADHAND appeared higher than those reported in the pivotal tralokinumab monotherapy trials which may reflect differences in the ADHAND study design and patient population (e.g. shorter TCS wash‑out period, more restricted TCS rescue use, and less severe patient population).2 These findings further support tralokinumab as a therapeutic option for patients with AD and moderate-to-severe hand involvement.