Clinical Effectiveness of Antifibrotic Medications for Idiopathic Pulmonary Fibrosis

Rationale: Since their approval, there has been no real-world or randomized trial evidence evaluating the effect of the antifibrotic medications pirfenidone and nintedanib on clinically important outcomes such as mortality and hospitalizations. Objectives: To evaluate the clinical effectiveness of the antifibrotic medications pirfenidone and nintedanib in patients with idiopathic pulmonary fibrosis. Methods: Using a large U.S. insurance database, we identified 8,098 patients with idiopathic pulmonary fibrosis between October 1, 2014 and March 1, 2018. A one-to-one propensity score-matched cohort was created to compare patients treated with antifibrotic medications (n = 1,255) with those not on treatment (n = 1,255). The primary outcome was all-cause mortality. The secondary outcome was acute hospitalizations. Subgroup analyses were performed to evaluate mortality differences by drug. Measurements and Main Results: The use of antifibrotic medications was associated with a decreased risk of all-cause mortality (hazard ratio [HR], 0.77; 95% confidence interval [CI], 0.62-0.98; P value = 0.034). However, this association was present only through the first 2 years of treatment. There was also a decrease in acute hospitalizations in the treated cohort (HR, 0.70; 95% CI, 0.61-0.80; P value <0.001). There was no significant difference in all-cause mortality between patients receiving pirfenidone and those on nintedanib (HR, 1.14; 95% CI, 0.79-1.65; P = 0.471). Conclusions: Among patients with idiopathic pulmonary fibrosis, antifibrotic agents may be associated with a lower risk of all-cause mortality and hospitalization compared with no treatment. Future research should test the hypothesis that these treatments reduce early, but not long-term, mortality as demonstrated in our study.