Drug-induced interstitial lung disease: a real-world pharmacovigilance study of the FDA Adverse Event Reporting System from 2004 to 2021

Abstract

Background: Drug-induced interstitial lung disease (DILD) is an increasingly common cause of morbidity and mortality. However, due to the lack of specificity, DILD detection remains an unsolved public health challenge. Objectives: For the first time, we aimed to examine DILD reports submitted to the Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) to identify demographic characteristics and top drugs associated with DILD at a group level (including age, sex, drug class, and country stratification) and individual drug level. Design: A retrospective analysis of the FAERS database was examined by disproportionality analysis. Methods: We reviewed the FAERS database from 2004 to 2021, using search terms ‘interstitial lung disease’ and sorting cases by generic drug name. The reporting odds ratio, proportional reporting ratio, and Bayesian confidence propagation neural network were calculated as the measure of strength of association. Results: There were 32,821 DILD reports in the FAERS. After excluding reports without age, sex, or country data according to the specific measurement, the median age of patients was 68 (interquartile range: 59), 54.77% were male, and 46.00% of reports came from Japan. The top drug classes related to DILD in the FAERS were antineoplastic, followed by cardiovascular and antirheumatic agents, in varying order in different sexes. Fam-trastuzumab deruxtecan-nxki, ramucirumab, and eribulin were the top three drugs with the highest strength of association. We also found some drugs without DILD in the labels, such as amiodarone, temsirolimus, and ursodiol. There are significant differences in DILD reports in various countries. For example, the United States and France reported more cardiovascular agents, whereas Canada reported more antirheumatic agents. Conclusion: We found the top drugs and drug classes that were associated with DILD in the FAERS, which provides a real-world window for different ages, sexes, and countries to formulate precise pharmacovigilance policies.