Drug-induced interstitial lung disease: a pharmacovigilance study of twelve immunomodulatory and antineoplastic agents.

BACKGROUND: Drug-induced interstitial lung disease (ILD) is a potentially severe pulmonary complication associated with various immunomodulatory and antineoplastic agents. Despite increasing recognition, comparative disproportionality data across drug classes remain limited. METHODS: We conducted a retrospective pharmacovigilance study using the FDA Adverse Event Reporting System (FAERS, 2004–2024). Twelve agents with known or suspected associations with ILD were selected. For each drug, the total number of adverse events and ILD reports were extracted. The proportional reporting ratio and reporting odds ratios (RORs) with 95% confidence intervals (CIs) were calculated to assess disproportionality. RESULTS: Methotrexate and rituximab accounted for the highest number of ILD reports. Amiodarone hydrochloride showed the highest proportion of ILD among its adverse events (9.4%) and the strongest disproportionality signal (ROR = 7.11; 95% CI: 6.79–7.45). Elevated RORs were also noted for leflunomide (3.05), tocilizumab (1.94), pembrolizumab (1.89), and methotrexate (1.90). In contrast, TNF-α inhibitors such as adalimumab (ROR = 0.29) and etanercept (ROR = 0.34) were associated with lower disproportionality signals. CONCLUSION: Significant variation in ILD signal strength was observed across drug classes. Amiodarone and leflunomide showed disproportionately strong ILD signals, while TNF-α inhibitors demonstrated lower reporting frequencies. These findings underscore the need for ongoing pharmacovigilance when using agents with potential pulmonary toxicity.