Post-marketing safety concerns with pirfenidone and nintedanib: an analysis of individual case safety reports from the FDA adverse event reporting system database and the Japanese adverse drug event report databases

作者：Tao Wang, Zhiwei Cui, Yingyong Ou, Siyu Lou, Huayou Chen, Chengyu Zhu, Linmei Zhou, Fan Zou · 发表于：Frontiers in Pharmacology · 年份：2025 · DOI：10.3389/fphar.2025.1530697 · 被引用次数：6 · 研究领域：Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis、Pharmacovigilance and Adverse Drug Reactions、Lung Cancer Treatments and Mutations

Introduction: To date, only two drugs, pirfenidone and nintedanib, are approved for the treatment of patients with idiopathic pulmonary fibrosis (IPF). In addition, very few studies have reported on the safety profile of either drug in large populations. This study aims to identify and compare adverse drug events (ADEs) associated with pirfenidone and nintedanib in real-world settings by analyzing data from the US Food and Drug Administration Adverse Event Reporting System (FAERS). In addition, we utilized data from the Japanese Adverse Drug Event Report (JADER) database for external validation. Methods: The ADE reports on both drugs from 2014 Q3 to 2024 Q2 in FAERS and from 2008 Q1 to 2024 Q1 in JADER were collected. After deduplication, Bayesian and non-Bayesian methods for disproportionality analysis, including Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Multiple Gamma Poisson Shrinkers (MGPS), were used for signal detection. Additionally, time to onset (TTO) analysis were performed. Results: In total, 35,804 and 20,486 ADE reports were identified from the FAERS database for pirfenidone and nintedanib, respectively. At the system organ class (SOC) level, both drugs have a positive signal value for "gastrointestinal disorders," "respiratory, thoracic, and mediastinal disorders," and "metabolism and nutrition disorders." Other positive signals for pirfenidone include "general disorders and admini...