A Durability Index for Atopic Dermatitis: Indirect Comparison of Lebrikizumab, Dupilumab, and Tralokinumab in Maintaining Efficacy Under Variable Treatment Adherence

INTRODUCTION: Real-world management of moderate-to-severe atopic dermatitis (AD) may involve treatment interruptions. This indirect comparison evaluated the efficacy of lebrikizumab, dupilumab, and tralokinumab monotherapy in achieving week-52 response at variable adherence levels. METHODS: This indirect comparative analysis used data from the induction (week 0-16) and maintenance (week 16-52) phases of the ADvocate, SOLO, and ECZTRA monotherapy trials. A novel Durability Index (DI) was used to estimate week 52 response from week 0 at variable maintenance adherence levels. To estimate the impact of adherence, reported maintenance responses in the continuous treatment (100% adherence) and withdrawal (0% adherence) arms were weighted by the assumed proportion of patients remaining on treatment, with intermediate adherence levels estimated by linear interpolation. Responses included an Investigator's Global Assessment (IGA) score of 0/1 or ≥ 75% improvement in Eczema Area Severity Index (EASI 75). Odds ratios (ORs) and risk differences (RD) with 95% confidence intervals (CIs) were estimated. RESULTS: Lebrikizumab had significantly greater efficacy than dupilumab of achieving week 52 IGA 0/1 for adherence rates between 0% (OR 3.4, 95% CI 1.3-11.3) and 78% (OR 1.5, 1.0-2.5) and EASI 75 for adherence rates between 0% (OR 2.6, 1.4-5.0) and 63% (OR 1.4, 1.0-2.0). At higher adherence rates, lebrikizumab had comparable efficacy to dupilumab. Lebrikizumab had significantly better efficacy than tralokinumab of achieving week 52 responses for all adherence rates for IGA 0/1 (0%: OR 2.5, 1.1-5.9; 100%: OR 2.6, 1.6-4.2) and EASI 75 (0%: OR 5.3, 2.8-10.4; 100%: OR 3.2, 2.2-4.8). Dupilumab had significantly better efficacy than tralokinumab of achieving IGA 0/1 at adherences rates above 69% and EASI 75 across all adherence rates. RDs were consistent with differences observed for ORs. CONCLUSIONS: In this indirect comparative analysis, lebrikizumab was associated with comparable or superior efficacy relative to dupilumab and superior efficacy relative to tralokinumab across all adherence rates in moderate-to-severe AD. As the DI is a novel metric, these findings should be interpreted cautiously, and independent validation of the DI is needed to ensure its clinical utility.