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

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Jonathan Silverberg
Thomas Bieber
Amy Paller
Lisa Beck
Masahiro Kamata
Luis Puig
Marni Wiseman
Khaled Ezzedine
Peter Foley
Erin Johansson
Martin Dossenbach
Bülent Akmaz
Marta Casillas
Andrei Karlsson
Raj Chovatiya

Keywords

network meta-analysis, atopic dermatitis, lebrikizumab

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.

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