Tralokinumab monotherapy rapidly improves sleep, daily functions, and health-related quality of life in patients with atopic dermatitis and moderate-to-severe hand involvement

Introduction: Atopic dermatitis (AD) is a chronic, inflammatory skin disease that typically affects multiple body areas with involvement of the hands being particularly burdensome, which can negatively impact patients’ emotional well-being and daily function. Health-related quality of life (HRQoL) measures may be more informative than standard clinical endpoints in understanding patient-perceived severity involving high-burden areas. ADHAND (NCT05958407) evaluated targeted IL-13 inhibition with tralokinumab in adults with AD and moderate-to-severe hand involvement. At Week 16, tralokinumab versus placebo significantly improved signs and symptoms of atopic hand eczema and its impact on HRQoL, with sustained or further improvements with continued tralokinumab treatment through Week 32. Here, we further assess tralokinumab monotherapy versus placebo on patient HRQoL outcomes in ADHAND, as measured by the general Dermatology Life Quality Index (DLQI) and the hand eczema-specific Hand Eczema Impact Scale (HEIS). Methods: Adults in ADHAND were randomized 2:1 to receive tralokinumab monotherapy 300 mg once every two weeks (Q2W) or placebo for 16 weeks. From Weeks 16-32, all patients received open-label tralokinumab Q2W. Analyses included the proportion of patients achieving a clinically meaningful improvement in DLQI (≥4-point reduction), the proportion of patients achieving a clinically meaningful improvement in HEIS (≥1.3-point reduction) and the mean change from baseline in individual HEIS domain scores. Statistical analyses followed pre‑specifications, with data after rescue or discontinuation due to adverse events or lack of efficacy handled using nonresponder imputation (for binary endpoints) or last observation carried forward (for continuous endpoints); multiple imputation was applied to all other missing data. Results: A total of 235 patients were randomized to tralokinumab (N=156) and placebo (N=79). At Week 16, a significantly greater proportion of patients who received tralokinumab achieved a ≥4-point improvement in DLQI compared with placebo (76.6% vs 44.7%; difference: 31.8%, 95% CI: 18.7-44.9; P<.001) and achieved a ≥1.3-point improvement in HEIS (59.7% vs 22.8%; difference: 36.9, 95% CI: 24.3-49.5; P<.001). Early separation between treatment groups was observed within 2 weeks for both outcomes. Response rates continued to improve with continuous tralokinumab treatment up to Week 32 in the open-label period, with clinically meaningful improvements in DLQI and HEIS observed in 89.6% (112/125) and 83.2% (99/119) of patients, respectively. At Week 16, greater improvements were observed across all individual HEIS domains in the tralokinumab group versus placebo, with differences evident by Week 2. Mean percentage change from baseline to Week 16 with tralokinumab versus placebo were observed for proximal daily activity limitations (–63.3% vs –24.5%), embarrassment related to hand eczema (–59.4% vs –22.4%), frustration due to hand eczema (–58.1% vs –25.3%), impact on quality of sleep (–68.5% vs –24.3%), difficulty working (–72.5% vs –32.7%), and difficulties with physical functions (–74.6% vs –29.8%) (all P<.001). Conclusion: Tralokinumab provided clinically meaningful improvements in HRQoL, as measured by both dermatology-specific (DLQI) and hand eczema-specific (HEIS) measures, in patients with AD and moderate-to-severe hand involvement. Further improvements were observed with continued treatment up to Week 32. In addition, statistically significant improvements across all HEIS domains were observed at Week 16.