Pirfenidone reduces the risk of lung cancer development in IPF: a nationwide population based study

<bold>Background:</bold> Idiopathic pulmonary fibrosis (IPF) carries a high risk of lung cancer, but the effect of pirfenidone on lung cancer development remains uncertain. We investigated the association between pirfenidone use and lung cancer development in patients with IPF. <bold>Methods:</bold> We included 10,084 patients with IPF from the national claims database. Propensity score analysis with inverse probability of treatment weighting (IPTW) and landmark analyses were employed to evaluate lung cancer occurrence according to pirfenidone use. The association was evaluated using Cox regression models adjusted for clinical and socioeconomic variables. An independent single-center idiopathic pulmonary fibrosis cohort (n=941) was used for validating the findings. <bold>Results:</bold> The mean patient age was 69.4 years, 73.8% were men, and 31.6% received pirfenidone. Lung cancer developed in 766 patients with IPF (7.6%; 21.9 cases per 1000 person-years) during a median follow-up of 3.0 years; the pirfenidone group showed lower incidence (10.4 vs. 27.9 cases per 1,000 person-years) than the no-pirfenidone group (figure 1a:original cohort, 1b: IPTW cohort). Landmark analysis at 6 months postdiagnosis showed lower incidence of lung cancer in the pirfenidone group than that of the no-pirfenidone group. Pirfenidone use was independently associated with a reduced lung cancer risk (weighted adjusted hazard ratio: 0.347; 95% confidence interval: 0.258–0.466). A validation cohort showed similar association (adjusted hazard ratio: 0.325; 95% confidence interval: 0.144–0.731). <bold>Conclusion:</bold> Pirfenidone use may be associated with a reduced lung cancer risk in patients with IPF.