Efficacy Comparison of Targeted Systemic Monotherapies Including Lebrikizumab for Moderate-to-Severe Atopic Dermatitis: a Network Meta-Analysis

Abstract

Background: Atopic dermatitis (AD) is a chronic inflammatory skin disease affecting 2–7% of adults globally, with 30% experiencing moderate-to-severe disease. Although several treatments for moderate-to-severe AD are available, the efficacy of many treatments has not been compared in head-to-head trials. Using a network meta-analysis (NMA), we evaluated the relative efficacy between lebrikizumab, an emerging biologic, and approved targeted systemic treatments for AD.

Methods: Double-blind, randomized, placebo-controlled clinical trials (systemic monotherapy-only) for moderate-to-severe AD in adults (≥18 years) and adolescents (≥12 years to ≤18 years) published before April 2023 were identified in a systematic literature review. Data were extracted for short-term (12–16 weeks) efficacy outcomes (Investigator’s Global Assessment [IGA] 0/1 with ≥2-point improvement from baseline and the Eczema Area and Severity Index [EASI]) and patient-reported outcomes (Peak Pruritus Numeric Rating Scale [PP-NRS] with ≥4-point improvement from baseline). Bayesian NMAs were performed using random-effects models, with baseline-risk adjustment. Key estimates from the NMAs included pairwise differences between all treatments and absolute response rates for each treatment.

Results: Twenty-three clinical trials were included. For % achieving IGA 0/1, at 12–16 weeks, the estimated response rates (posterior median and 95% credible interval) for each of the treatments were: upadacitinib 30 mg 56% (46–65%), upadacitinib 15 mg 42% (32–50%), abrocitinib 200 mg 38% (31–45%), lebrikizumab 250 mg 32% (25–40%), dupilumab 300 mg 32% (24–39%), abrocitinib 100 mg 26% (20–32%), tralokinumab 300 mg 18% (13–22%), baricitinib 4 mg 17% (10–25%), baricitinib 2 mg 16% (10–22%), and placebo 6% (5–8%). Similar trends were observed for the EASI and PP-NRS responses at 12–16 weeks.

Conclusion: This 16-week NMA analysis shows that lebrikizumab had a similar response rate to dupilumab, the most widely used targeted systemic therapy for AD, and may represent a valuable treatment alternative for moderate-to-severe AD.