Lebrikizumab Treatment Improves Lichenification and Other Clinical Signs of Atopic Dermatitis in Adults and Adolescents with Moderate-to-Severe AD and Skin of Color

Abstract

Introduction The ADmirable (NCT05372419) Phase 3b clinical trial was the first lebrikizumab (LEBRI) study in adults and adolescents with atopic dermatitis (AD) and skin of color (SOC), a historically underrepresented patient population in clinical trials. We conducted a post-hoc analysis to assess improvement in Eczema Area and Severity Index (EASI) clinical signs across four body regions with LEBRI in ADmirable at 24 weeks.

Methods In the ADmirable trial, 90 adults and adolescents (≥12 to <18 years; weight ≥40 kg) with moderate-to-severe AD who self-identified as non-White and had Fitzpatrick skin phototype IV-VI received open-label LEBRI 250 mg (500 mg loading dose at baseline [BL] and Week 2) every 2 weeks (Q2W) from Weeks 4-16. From Weeks 16-24, responders (Investigator’s Global Assessment score of 0 or 1 with a ≥2-point improvement or ≥75% improvement in EASI) received LEBRI 250 mg once every 4 weeks (Q4W); per-protocol non-responders continued with LEBRI 250 mg Q2W. Least-squares mean (LSM) of percent change from BL was analyzed using mixed model repeated measures with observed data; Q2W and Q4W populations were pooled Weeks 16-24. Concomitant low and mid-potency TCS and TCI use was allowed. Patients requiring rescue therapy were discontinued. EASI severity score assessed the intensity of erythema, edema/papulation, excoriation, and lichenification in four regions (head/neck, trunk, upper and lower extremities) with 0 being absent, 1 mild, 2 moderate, and 3 severe.

Results BL lichenification scores were lower in head/neck and trunk (1.7, 1.9, respectively) vs. upper and lower extremities (2.2 each). Erythema, edema/papulation, and excoriation followed a similar trend at BL. With LEBRI, LSM percent improvements were observed in each clinical sign over all body regions at Week 16 and were maintained or improved through Week 24. Lichenification scores decreased by 72.4% (head/neck), 73.1% (trunk), 59.5% (upper extremities), and 66.1% (lower extremities) by Week 16; and 76.0%, 78.9%, 72.1%, and 75.3%, respectively, at Week 24. The other clinical signs of AD showed similar improvement across all body regions at Week 16 and were maintained or further improved by Week 24.

Conclusions Lebrikizumab improved each clinical sign of skin severity assessed by EASI across all body regions in patients with moderate-to-severe AD and SOC, including lichenification, which may be more prominent in this understudied population.