Age-Dependent Differences in Canakinumab Safety: A Comprehensive Pharmacovigilance Analysis Using the FAERS Database

While the efficacy of canakinumab, an anti-interleukin-1β monoclonal antibody, is well-established, its safety profile, particularly across different age groups, remains inadequately explored. Using the FDA Adverse Event Reporting System (FAERS) database, this study evaluated postmarketing safety by analyzing adverse event (AE) reports from 2010 onward, with canakinumab as the primary suspected drug. Disproportionality analysis employed four algorithms-reporting odds ratio (ROR), proportional reporting ratio, multi-item gamma Poisson shrinker, and Bayesian confidence propagation neural network-to detect safety signals, and the Weibull distribution was used to model the temporal risk of AEs. 9262 canakinumab-related AE reports were analyzed. Significant signals were detected across multiple system organ classes (SOCs), most prominently general disorders and administration site conditions (n = 6765; ROR 1.47) and infections and infestations (n = 3532; ROR 2.54). Age-stratified analyses revealed distinct AE profiles: pyrexia, inappropriate schedule or dose of administration, and gastrointestinal and hepatobiliary disorders (e.g., abdominal pain, hepatitis) were most frequently reported in individuals < 12 years, as well as leukopenia in adolescents (12-17 years). Older patients (≥ 65 years) most frequently reported pneumonia, sepsis, and cellulitis, with strong signals for neoplasms. Temporal analysis revealed an early failure pattern, but ~40% of AEs occurred after 1 year. These findings underscore significant safety signals associated with canakinumab, including infections, gastrointestinal/hepatobiliary disorders in children, and neoplasms in older patients. The dual temporal pattern of AEs underscores the need for both short- and long-term surveillance.