Drug-Gene Risk Stratification in Patients with Suspected Drug-Induced Interstitial Lung Disease

Marjolein Drent (), Petal A. Wijnen, Naomi T. Jessurun, Ankie M. Harmsze, Otto Bekers and Aalt Bast
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Marjolein Drent: Maastricht University
Petal A. Wijnen: St. Antonius Hospital
Naomi T. Jessurun: ILD Care Foundation
Ankie M. Harmsze: St. Antonius Hospital
Otto Bekers: Maastricht University
Aalt Bast: Maastricht University

Drug Safety, 2024, vol. 47, issue 4, No 5, 355-363

Abstract: Abstract Background Pulmonary toxicity has been associated with drug use. This is often not recognized in clinical practice, and underestimated. Objective We aimed to establish whether polymorphisms in certain genes corresponding with a metabolic pathway of drug(s) used are associated with pulmonary toxicity in patients with suspected drug-induced interstitial lung disease (DI-ILD). Methods This retrospective observational study explored genetic variations in three clinically relevant cytochrome P450 (CYP) iso-enzymes (i.e., CYP2D6, CYP2C9, and CYP2C19) in a group of patients with a fibroticinterstitial lung disease, either non-specific interstitial pneumonia (n = 211) or idiopathic pulmonary fibrosis (n = 256), with a suspected drug-induced origin. Results Of the 467 patients, 79.0% showed one or more polymorphisms in the tested genes accompanied by the use of drug(s) metabolized by a corresponding affected metabolic pathway (60.0% poor metabolizers and/or using two or more drugs [likely DI-ILD], 37.5% using three or more [highly likely DI-ILD]). Most commonly used drugs were statins (63.1%) with a predominance among men (69.4 vs 47.1%, p

Date: 2024
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DOI: 10.1007/s40264-024-01400-0

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