Efficacy and Safety of Lebrikizumab in Adults with Moderate-to-Severe Atopic Dermatitis: A Systematic Review and Meta-Analysis

<b>Background</b>: Atopic dermatitis (AD) is a chronic inflammatory skin disease associated with substantial symptom burden and impaired quality of life. Lebrikizumab, a monoclonal antibody targeting interleukin-13, has emerged as a therapeutic option for patients with moderate-to-severe AD; however, a comprehensive synthesis of its efficacy and safety is required. <b>Methods</b>: We conducted a systematic review and meta-analysis of randomized controlled trials comparing lebrikizumab with placebo in patients with moderate-to-severe AD. Searches were performed across major databases and trial registries. The primary outcome was achievement of a 50% improvement in the Eczema Area and Severity Index (EASI-50). Secondary efficacy outcomes included EASI-75, EASI-90, and improvement in pruritus measured by the Numeric Rating Scale (NRS). Safety was assessed through a quantitative meta-analysis of treatment-emergent adverse events (TEAEs) when extractable arm-level data were available. Random-effects models were applied, and certainty of evidence was evaluated using the GRADE framework. <b>Results</b>: Twelve randomized controlled trials were included. Lebrikizumab significantly increased the likelihood of achieving EASI-50 (RR 1.51, 95% CI 1.20-1.89), EASI-75 (RR 1.78, 95% CI 1.43-2.22), and EASI-90 (RR 2.26, 95% CI 1.67-3.06) compared with placebo, and was associated with clinically meaningful improvement in pruritus (RR 1.73, 95% CI 1.38-2.17). Substantial heterogeneity was observed for EASI-75 (I² = 77.5%); predefined subgroup analyses based on dosing regimen and dosing frequency partially explored this variability, but residual heterogeneity persisted, leading to downgrading of the certainty of evidence for EASI-75 to low. The certainty of evidence was moderate for EASI-50 and low for EASI-90 and pruritus improvement. Six trials contributed to the quantitative safety analysis. The pooled meta-analysis showed no significant difference in the risk of treatment-emergent adverse events between lebrikizumab and placebo (RR 1.03, 95% CI 0.82-1.28), with moderate heterogeneity (I² = 60.5%). Serious adverse events and treatment discontinuations were infrequently reported and could not be pooled quantitatively due to inconsistent reporting. <b>Conclusions</b>: Lebrikizumab demonstrates clinically meaningful efficacy and a favorable safety profile in patients with moderate-to-severe atopic dermatitis. However, as the available randomized evidence is predominantly derived from adult populations, the applicability of these findings to adolescents remains limited and warrants confirmation in adequately powered, adolescent-focused studies.