Clinical profiles and risk predictors of drug-induced liver injury from pirfenidone and nintedanib used to treat idiopathic pulmonary fibrosis: a real-world analysis of a tertiary Chinese hospital cohort combined with FAERS data mining.

BACKGROUND

Drug-induced liver injury (DILI) is a known significant adverse effect of pirfenidone and nintedanib, essential antifibrotic agents for idiopathic pulmonary fibrosis (IPF). However, real-world evidence on the risk profiles is limited. We aimed to describe the clinical profiles and identify risk factors for antifibrotic DILI in real-world practice to inform risk mitigation strategies.

METHODS

A retrospective case-control study was conducted among patients receiving pirfenidone at our tertiary hospital between October 2011 and December 2022 (approval No. ES-2024-K064-01). Hepatic safety signals were also evaluated through disproportionality analysis of the Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) using reporting odds ratios (RORs).

RESULTS

For pirfenidone, among 3,199 treated patients, 63 (3.18%) developed DILI, typically within two weeks of therapy initiation. Significant risk factors included body mass index (BMI) ≤23.9 kg/m2 [odds ratio (OR) =7.32, P<0.001], ≥4 comorbidities (OR =7.18, P<0.001), pre-existing liver disease (OR =3.31, P=0.004), and alcohol consumption (OR =4.52, P=0.002). FAERS analysis recorded 904 hepatic adverse event (AE) reports, with 338 positive signals, most involving men aged 65-74 years and occurring within 30 days of initiation (6.89%). For nintedanib, 3.2% of exposed patients experienced DILI. FAERS analysis documented 2,114 hepatic AE reports, with 1,634 positive signals, predominantly in men aged 65-74 years, with 30.29% occurring within 30 days of initiation.

CONCLUSIONS

Both pirfenidone and nintedanib carry notable hepatotoxicity risks. Close liver function monitoring is advised during early treatment, especially in patients with low BMI, multiple comorbidities, pre-existing liver disease, or alcohol consumption.