Efficacy and Safety of Pirfenidone in Advanced Versus Non-Advanced Idiopathic Pulmonary Fibrosis: Post-Hoc Analysis of Six Clinical Studies

Introduction: In the European Union (EU), the indication for the antifibrotic pirfenidone prior to April 2023 did not include patients with advanced idiopathic pulmonary fibrosis (IPF). This analysis compared the efficacy and safety of pirfenidone in advanced IPF versus non-advanced IPF. Methods: Data were included from the following studies of pirfenidone: ASCEND (NCT01366209); CAPACITY (004 [NCT00287716] and 006 [NCT00287729]); RECAP (NCT00662038; advanced IPF defined as percent predicted forced vital capacity [%FVC] < 50% and/or percent predicted carbon monoxide diffusing capacity [%DLco] < 35% at baseline); PASSPORT (NCT02699879; advanced IPF defined as baseline %FVC < 50%); and SP-IPF (NCT02951429; patients with advanced IPF [defined as %DLco ≤ 40% at screening] at risk of group 3 pulmonary hypertension). Results: In the pooled ASCEND/CAPACITY studies, the annual mean rate of FVC decline from baseline to Week 52 was significantly lower for pirfenidone versus placebo in advanced (p = 0.0035) and non-advanced IPF (p = 0.0001). Rate of all-cause mortality over 52 weeks was numerically lower for pirfenidone versus placebo in advanced and non-advanced IPF. In RECAP, the mean annual rate of FVC decline from baseline to Week 180 of pirfenidone treatment was similar in patients with advanced (− 141.5 mL) and non-advanced IPF (− 153.5 mL). In SP-IPF, the mean annual rate of FVC decline and rate of all-cause mortality from baseline to Week 52 in patients treated with placebo + pirfenidone were − 93.0 mL and 20.2%, respectively. No new safety signals were identified, and the safety profile of pirfenidone in patients with advanced IPF was generally consistent with that of non-advanced IPF. Conclusions: These results highlight the benefit of pirfenidone treatment in patients with advanced and non-advanced IPF. As such, the indication for pirfenidone in the EU has now been updated to include the treatment of adult patients with advanced IPF. Trial Registrations: ASCEND (NCT01366209), CAPACITY 004 (NCT00287716), CAPACITY 006 (NCT00287729), RECAP (NCT00662038), PASSPORT (NCT02699879), and SP-IPF (NCT02951429).