Efficacy and Safety of Lebrikizumab in Adult and Adolescent Patients with Skin of Color and Moderate-to-Severe Atopic Dermatitis: Results from the Phase IIIb, Open-Label ADmirable Study.

Abstract

Background: Data are lacking to guide diagnosis and treatment in patients with skin of color and atopic dermatitis (AD), a population traditionally underrepresented in clinical trials.

Objective: The aim of this study was to evaluate the efficacy and safety of lebrikizumab in adults and adolescents with skin of color and moderate-to-severe AD.

Methods: In the open-label ADmirable trial, 90 adults and adolescents with moderate-to-severe AD, Fitzpatrick skin phototype IV-VI, and self-reported race other than White received lebrikizumab 250 mg subcutaneously every 2 weeks (Q2W), following a 500-mg loading dose at baseline and Week 2, for 16 weeks. From Week 16 to Week 24, responders, defined as patients with at least 75% improvement in Eczema Area and Severity Index (EASI 75) and/or Investigator's Global Assessment (IGA) score of 0/1 with at least a 2-point improvement from baseline, received lebrikizumab every 4 weeks (Q4W); inadequate responders continued lebrikizumab Q2W. The primary endpoint was the percentage of patients achieving EASI 75 at Week 16. Secondary and exploratory efficacy endpoints and safety were assessed throughout. Data were analyzed as observed and using imputation, with Q2W and Q4W populations pooled for Weeks 16-24.

Results: Mean age at baseline was 40.7 years; 43.3% were female; and 43.3%, 24.4%, and 32.2% had Fitzpatrick skin phototypes IV, V, and VI, respectively. Baseline mean EASI and Pruritus Numeric Rating Scale (NRS) scores were 26.4 and 7.0, respectively; 68.9% of patients had moderate disease (IGA = 3). At Week 16 (number of patients with non-missing values [Nx] = 78), EASI 75, EASI 90 (≥ 90% improvement from baseline in EASI), and IGA 0/1 (IGA response of clear or almost clear) were achieved by 69.2%, 44.9%, and 44.9% of patients, respectively; for Pruritus NRS (Nx = 62), 58.1% of patients reported ≥ 4-point improvement. At Week 24 (Nx = 74) (pooled treatment arms), EASI 75, EASI 90, and IGA 0/1 were achieved by 78.4%, 47.3%, and 54.1% of patients, respectively. EASI 75 was achieved by 62.9%, 88.2%, and 95.5% of patients with Fitzpatrick skin phototype IV (Nx = 35), V (Nx = 17), and VI (Nx = 22), respectively, at Week 24. Most patients (64.4%) with baseline PDCA-Derm™-assessed hyperpigmented areas showed reduced hyperpigmentation at Week 24. Most treatment-emergent adverse events were mild or moderate in severity; none were serious or led to discontinuation. One case of conjunctivitis was reported.

Conclusion: In this first lebrikizumab study in patients with skin of color (Fitzpatrick skin phototype IV, V, and VI) and moderate-to-severe AD, lebrikizumab improved signs and symptoms of AD and confirmed its favorable safety profile.

Trial registration: ClinicalTrials.gov Identifier: NCT05372419 (registered May 5, 2022).