Psychiatric Adverse Events Associated With Lebrikizumab: An FDA Adverse Event Reporting System (FAERS) Disproportionality Analysis With an Indication-Matched Active Comparator

Introduction: Lebrikizumab, an anti-interleukin-13 antibody approved for moderate-to-severe atopic dermatitis, has not been evaluated for psychiatric adverse event reporting, although dupilumab and tralokinumab, which act on the same pathway, have generated postmarketing psychiatric signals, most consistently for sleep disturbance.Methods: We performed a disproportionality analysis of FDA Adverse Event Reporting System (FAERS) reports accessed through the FDA Health Informatics initiative, openFDA (data through July 30, 2026), reported according to the READUS-PV (REporting of A Disproportionality analysis for drUg Safety signal detection using individual case safety reports in PharmacoVigilance) guideline.All exposure arms and the whole-database reference were restricted to reports received from September 2024, when lebrikizumab was approved in the United States, through June 2026.Reporting odds ratios (RORs) with 95% confidence intervals (CIs) compared lebrikizumab with an indication-matched active comparator (dupilumab and tralokinumab) and, contextually, with the entire database, for a composite of psychiatric MedDRA (Medical Dictionary for Regulatory Activities) preferred terms from which any term showing a comparator-specific signal against the whole database was removed by a prespecified rule.Results: The analysis included 1,743 lebrikizumab, 142,906 dupilumab, and 3,315 tralokinumab reports.Of 51 psychiatric terms identified, five were excluded for comparator-specific signals.For the 46-term composite, 38 lebrikizumab reports (2.2%) and 2,716 pooled comparator reports (1.9%) qualified; the ROR was 1.18 (95% CI, 0.85 to 1.63) against the pooled comparator, 1.17 (95% CI, 0.85 to 1.62) against dupilumab, 1.37 (95% CI, 0.90 to 2.09) against tralokinumab, and 0.42 (95% CI, 0.31 to 0.58) against the whole database.The full 51-term composite gave RORs of 0.44 to 0.77, the difference attributable to the excluded terms.A composite without sleep-wake terms gave 1.40 (95% CI, 0.94 to 2.06) against the pooled comparator and 2.08 (95% CI, 1.19 to 3.63) against tralokinumab.Nervousness and anxiety were nominally elevated against dupilumab and the pooled comparator; no term remained significant after Benjamini-Hochberg correction.Conclusions: Within a common reporting period, psychiatric adverse events were not reported disproportionately for lebrikizumab relative to dupilumab or to the pooled indication-matched comparator.The higher estimates against tralokinumab alone rest on small numbers and warrant replication.These findings characterize reporting, not risk.