Title : Comparing lebrikizumab with other systemic immunomodulators for moderate to severe atopic dermatitis: An updated systematic review
Abstract:
Background: Atopic dermatitis (AD) is a long-term inflammatory skin disease that requires prolonged management with systemic therapy. Treatment with lebrikizumab results in apoptosis of effector T helper 2 (TH2) cells that produce interleukin-13 (IL-13).
Aim: The study aims to conduct a systematic literature review on the comparative efficacy of lebrikizumab monotherapy versus other approved biologics and the short-term efficacy of Janus kinase (JAK) inhibitors in moderate-to-severe AD in adults and adolescents.
Methods: A systematic database search was conducted to identify randomized, double-blind, placebo-controlled phase 2 and phase 3 trials of lebrikizumab, dupilumab, tralokinumab, abrocitinib, baricitinib, and upadacitinib used as monotherapy, from database inception through December 2025. Efficacy measurements comprised Eczema Area and Severity Index (EASI) responses, Investigator Global Assessment (IGA) 0/1, and pruritus Numeric Rating Scale (NRS) improvements. Two independent reviewers screened studies, and inter-reviewer agreement was assessed using Cohen's kappa statistic. The Cochrane Risk of Bias tool and the GRADE system assessed the quality of the evidence, with data extraction performed by independent reviewers.
Results: A total of 28 studies with 10,847 patients were evaluated (22 from the previous review and six new studies). The level of agreement among reviewers for study selection was substantial, with a kappa statistic of 0.89. Dosing intervals are reported as every 2 weeks (Q2W). According to 22 trials of network meta-analysis (NMA), lebrikizumab 250 mg every two weeks was as effective as dupilumab 300 mg every two weeks for IGA 0/1. There was an equal improvement in EASI and itch score at weeks 12-16. Lebrikizumab was more efficacious than tralokinumab and baricitinib on outcomes. A total of 2,316 patients were included in six new studies designed to confirm these results in real-world evidence (RWE) settings 2024-2025, with EASI-75 and IGA 0/1 response rates of 65-78% and 58-72%, respectively. Data on a two-year extension demonstrated sustained efficacy and acceptable safety. The risk of bias generally resulted in moderate-quality evidence.
Conclusions: An updated review of 28 studies shows that lebrikizumab is at least as efficacious as dupilumab and more efficacious than tralokinumab in moderate-to-severe atopic dermatitis. There is real-world and long-term data to support its first-line use with moderate to high certainty, but complete, 736 trials, head-to-head trials, and biomarker research remain needed.
