Assessing the Risk of Drug-Induced Influenza-Like Illness: A Disproportionality Analysis of Two Decades of FAERS Data...

With the rising incidence of Influenza-like Illness (ILI), comprehensive studies on causative drugs remain lacking. This study aimed to detect drugs associated with ILI through disproportionality analysis of the FDA Adverse Event Reporting System (FAERS) database.

Adverse Event (AE) reports were extracted from the FAERS database for the period spanning 2004 Q1 through 2025 Q1. The Medical Dictionary for Regulatory Activities (MedDRA) was used to identify ILI cases. Four statistical methods were employed to identify drugs with positive signals: the Reporting Odds Ratio (ROR), the Proportional Reporting Ratio (PRR), the Bayesian Confidence Propagation Neural Network (BCPNN), and the Empirical Bayes Geometric Mean (EBGM).

Our analysis identified 77,060 ILI-associated reports. A total of 60 drugs exhibited positive signals. The 5 most frequently reported drugs were interferon β-1a, evolocumab, ofatumumab, interferon β-1b, and zoledronic acid. Under the ATC1 classification, antineoplastic and immunomodulating agents accounted for the majority of reported cases (n=43,436), followed by nervous system agents (n=8,941), cardiovascular system agents (n=6,871), and musculoskeletal system agents (n=5,577). Weibull shape parameter analyses revealed β<1 for most drugs, indicating that drug-induced ILI predominantly manifested early failure types.

This study confirms known ILI risks (e.g., interferons) and reveals new signals for immunotherapies and lipid-lowering agents, providing evidence for prescribing updates. Timeto- onset analysis shows declining risk over time, highlighting the need for early symptom monitoring.

This first comprehensive FAERS study identifies key drugs associated with ILI, including interferon β-1a, evolocumab, ofatumumab, interferon β-1b, and zoledronic acid. Clinical monitoring for drug-induced ILI is essential to enhance medication safety.