Exploring the Link Between Mtor Inhibitors and Interstitial Lung Diseases: A Disproportionality Analysis Using Fda Adverse Event Reporting System Database

Abstract

Abstract Background: The mammalian target of rapamycin (mTOR) inhibitors are immunosuppressive agents used to prevent organ transplant rejection. This class of drugs has shown significant high incidence of interstitial lung disease (ILD). Objective: This study aims to find out the potential safety signal associated between mTOR inhibitors and ILD by Food and Drug Administration Adverse Event Reporting System (FAERS) databases. Methods: Publicly available FAERS database was used to perform a case/non-case retrospective disproportionality analysis (2009Q1 to 2022Q3). OpenVigil 2.1MedDRA v24 was used to extract and filter data from FAERS database. The preferred term used for the study was “interstitial lung disease” and the drugs included ere everolimus, sirolimus and temsirolimus. Reporting odds ratio (ROR), proportional reporting ratio (PRR) and information component (IC) were used to detect signal. Results: Overall, 62,117 AE reports related to mTOR inhibitors were recorded during the period. Of these 1,027 AE reports on ILD were submitted to the FAERS database. Everolimus accounted for 723, sirolimus for 191 and temsirolimus for 113 cases of ILD reports associated with mTOR inhibitors. On performing age and gender stratification, it was found that the age group of 19-64yrs and female sex had the highest signal strength. Conclusion: This study has shown positive signals for ILD with everolimus, sirolimus, and temsirolimus which were not yet established in clinical trials. Further study with well-designed epidemiological data is required to validate these results.