D2.243 - Impact of simultaneous skin clearance and itch relief with lebrikizumab in patients with atopic dermatitis: post-hoc analysis from ADvocate1/2

Lebrikizumab (LEB), an interleukin-13 inhibitor with high affinity and slow dissociation rate, approved for moderate-to-severe atopic dermatitis (MtS AD), has shown efficacy in skin symptoms/itch in phase 3 trials. We analysed impact of simultaneous skin clearance/itch relief on HRQoL/disease burden at Week (W)16/52 using pooled ADvocate1/2 data (NCT04146363/NCT04178967). Lebrikizumab (LEB), an interleukin-13 inhibitor with high affinity and slow dissociation rate, approved for moderate-to-severe atopic dermatitis (MtS AD), has shown efficacy in skin symptoms/itch in phase 3 trials. We analysed impact of simultaneous skin clearance/itch relief on HRQoL/disease burden at Week (W)16/52 using pooled ADvocate1/2 data (NCT04146363/NCT04178967).

Adults and adolescents (≥12 years, ≥40 kg) with MtS AD were randomised 2:1 to LEB 250mg:placebo (PBO) every 2 weeks (Q2W) to W16 in ADvocate1/2. At W16, LEB responders (≥75% improvement in Eczema Area and Severity Index [EASI75]/Investigator’s Global Assessment 0/1 with ≥2-point improvement without rescue medication) were re-randomised 2:2:1 LEB Q4W:Q2W:PBO-LEB withdrawal through W52; topical rescue medication permitted. Skin clearance defined as EASI75; itch relief as Pruritus-Numerical Rating Scale ≥4-point improvement from baseline (BL; PNRS≥4). For patients (pts) with BL PNRS absolute score≥4, achievement of composite outcomes (PNRS≥4 and EASI75/90 or EASI score≤7 [mild disease severity]) was reported at W16/52. Missing data due to lack of efficacy or after rescue medication use were imputed as non-responders; other missing data using multiple imputation. At W16, LEB treated pts were stratified by achieving both EASI75+PNRS≥4 (Group 1), only one (Group 2) or neither (Group 3). Clinically meaningful HRQoL outcomes: Dermatology Life Quality Index (DLQI)0/1 and Sleep-Loss NRS (SLSS)0/1. Odds ratios (ORs) for Group 1&2 vs 3 were estimated using Firth logistic regression on observed data.

At W16, 31.9% (LEB Q2W) vs 5.2% (PBO) achieved EASI75+PNRS≥4; 22.1% vs 2.8% EASI90+PNRS≥4; 32.1% vs 5.8% EASI≤7+PNRS≥4 (all p<0.0001); significant results observed from W4. At W52 (Q4W/Q2W/PBO-LEB withdrawal), 52.1%/54.3%/45.2% achieved EASI75+PNRS≥4; 41.7%/45.0%/31.3% EASI90+PNRS≥4; 53.2%/52.0%/46.0% EASI≤7+PNRS≥4. Of 471 pts stratified at W16, 178 (38%) achieved EASI75+PNRS≥4 (Group 1), 170 (36%) only one (Group 2), 123 (26%) neither (Group 3). Clinically meaningful HRQoL outcomes were most frequent in Group 1, followed by Group 2&3; adjusted ORs for Group 1 vs 3 were consistently higher than corresponding ORs for Group 2 vs 3 (Table 1).

LEB had significantly higher rates of composite skin clearance and itch relief at W16 vs PBO as early as W4, with rates maintained to W52 in both dosing regimens. Achieving composite skin clearance and itch relief improved patient-reported HRQoL vs improvement of neither.