Antifibrotic therapy in familial idiopathic pulmonary fibrosis: a comparative cohort study.

Before the introduction of antifibrotic therapy, patients with familial pulmonary fibrosis (FPF) were reported to have a higher mortality risk than those with sporadic disease. Genetic predisposition plays an important role in the development of interstitial lung disease (ILD), including idiopathic pulmonary fibrosis (IPF). The 2023 European Respiratory Society consensus statement defined FPF and recommended antifibrotic drugs for treatment; however, their efficacy in FPF remains unclear. We conducted a retrospective multicohort study of 280 patients with IPF receiving antifibrotic therapy (exploratory cohort, n = 141; validation cohort, n = 139). FPF was defined as fibrotic ILD in at least two first- or second-degree relatives. We examined tolerability, causes of drug discontinuation, incidence of acute exacerbation (AE), and mortality. Among all patients, 45 (16.1%) had FPF-IPF. These patients were younger and included a lower proportion of men compared with sporadic IPF. No significant differences were observed between groups in drug tolerability, discontinuation causes, AE incidence, or mortality. Multivariate analyses adjusting for gender-age-physiology index confirmed that FPF was not associated with increased mortality. In conclusion, under antifibrotic therapy, FPF-IPF and sporadic IPF demonstrated comparable tolerability, risk of AE, and mortality.