Disproportionality Analysis of Adverse Events Associated with IL-1 Inhibitors in the FDA Adverse Event Reporting System (FAERS)

Background: Interleukin-1 (IL-1) inhibitors are approved for the treatment of various inflammatory diseases associated with immune system abnormalities. However, large-scale real-world studies to assess their security are still limited. Therefore, a pharmacovigilance study was conducted based on the data from the U.S. Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS). Methods: Adverse events (AEs) linked to IL-1 inhibitors were analyzed using the FAERS database from Q1 2004 to Q3 2024. Risk signals were identified through disproportionality analysis algorithms, including reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian confidence propagation neural network (BCPNN), and multi-item gamma Poisson shrinker (MGPS). Results: Among 17,670 AE reports where an IL-1 inhibitor was the “primary suspected” drug, 27 significant system organ classes (SOCs) were identified. Notable signals included infections and infestations (ROR: 2.31, 95% CI: 2.25–2.37) and congenital, familial, and genetic disorders (ROR: 2.26, 95% CI: 2.05–2.48). At the preferred term (PT) level, 263 significant AE signals were detected, such as pyrexia (ROR: 5.27, 95% CI: 5.03–5.53), nasopharyngitis (ROR: 2.31, 95% CI: 2.10–2.54), and injection site erythema (ROR: 6.09, 95% CI: 5.67–6.55). Importantly, we also identified less common or previously unreported AEs, including cardiac disorders (e.g., postural orthostatic tachycardia syndrome with anakinra; pulmonary valve incompetence with rilonacept) and endocrine disorders (e.g., secondary adrenocortical insufficiency with canakinumab). Furthermore, 36.33% of cases emerged after more than 360 days of treatment with IL-1 inhibitors. Conclusions: This study revealed real-world safety data on IL-1 inhibitors, providing important insights to enhance the clinical use of IL-1 inhibitors and minimize potential AEs.