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 cells that produce interleukin-13.

AIM

To conduct a systematic literature review on the comparative efficacy of lebrikizumab monotherapy vs other approved biologics and the short-term efficacy of Janus kinase 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 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 Grading of Recommendations Assessment, Development and Evaluation system assessed the quality of the evidence, with data extraction performed by independent reviewers.

RESULTS

A total of 28 studies with 10847 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, lebrikizumab 250 mg Q2W was as effective as dupilumab 300 mg Q2W 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 2316 patients were included in six new studies designed to confirm these results in real-world evidence 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.

CONCLUSION

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 AD. 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.

Keywords: Atopic dermatitis; Lebrikizumab; Dupilumab; Tralokinumab; Janus kinase inhibitors; Systematic review; Network meta-analysis; Grading of Recommendations Assessment, Development and Evaluation assessment

Core Tip: An updated systematic review of 28 studies (10847 patients) shows that the efficacy of lebrikizumab, a high-affinity anti-interleukin-13 monoclonal antibody, is equivalent to that of dupilumab and superior to that of tralokinumab in moderate-to-severe atopic dermatitis (AD). The results showed that lebrikizumab performs better than baricitinib and has efficacy comparable to that of most Janus kinase inhibitors. It also has a better safety profile, with no boxed warnings. Data from real-world and extension studies confirm sustained efficacy. Evidence of moderate to high quality suggests lebrikizumab is a reasonable first-line biologic for moderate to severe AD requiring systemic therapy.