Drug-induced interstitial lung disease: a nationwide observational study over 37 years using the French pharmacovigilance database

<bold>Background:</bold> Drug-induced interstitial lung disease (DI-ILD) is a heterogeneous subgroup of diffuse interstitial lung diseases (ILD). The number of identified molecules thought responsible for DI-ILD is increasing with time. Due to their low incidence, DI-ILDs may be detected only after a drug has been marketed, notably through Adverse Drug Reaction (ADR) reports to pharmacovigilance centres. The aim of our study was to describe DI-ILD cases notified to the French Pharmacovigilance Database (FPVD), reported clinical pictures and the potentially causal drugs. <bold>Methods:</bold> This retrospective study included cases registered in the FPVD from 1st January 1985 to 1st April 2022 which had ADR coded in MedDRA with a High Level Group Term “Lower respiratory tract disorders (excluding obstruction and infection)” involving patients aged 18 and over. <bold>Results:</bold> We analysed 7'234 cases involving 13’059 suspect medications and 1’112 specific pharmacological agents. 96.7% of cases were categorized as serious and in 13.3% death ensued. Men accounted for 54.4% of the cases. Median age was 69 y [18-103]. The most prevalent ADRs were "ILD" (51.0%), "Pulmonary oedema" (15.6%) and "Pulmonary fibrosis" (10.5%). "Anti-cancer drugs" (31.2%) and "Cardiovascular drugs" (29.1%) were the most prominent therapeutic classes involved, with amiodarone being the most commonly reported suspected drug (10.0%), followed by methotrexate (3.1%). <bold>Conclusion:</bold> This study, carried out on a national scale over 37 years, is the largest to date. DI-ILD are serious diseases with a potentially fatal course. Knowing how to make the diagnosis is essential in order to stop the culprit drug at an early stage.