Pirfenidone (PFD) effect on morbidity and mortality in patients with idiopathic pulmonary fibrosis (IPF)

Background: Three multinational, randomised, phase 3 trials of PFD (ASCEND and CAPACITY Studies) with similar study designs and populations have been performed in patients with IPF (N Engl J Med 2014; 370:2083-92; Lancet 2011; 377:1760-9). Data through the prespecified primary endpoint assessment in each study were pooled to provide robust estimates of the pirfenidone treatment effect. Methods: Analyses included all randomized patients and all observations through Week 52 in ASCEND and Week 72 in CAPACITY, and used Cox proportional hazards model and log rank test. Outcomes included time to FVC decline ≥10% or death, progression-free survival (FVC decline ≥10% or 6MWD decline ≥50 m or death), and 4 mortality outcomes. Results: A total of 1247 patients were analysed (PFD, N=623; placebo, N=624). PFD reduced FVC decline (hazard ratio [HR] 0.48; 95% confidence interval [CI] 0.37, 0.63), prolonged PFS (HR 0.62; 95% CI 0.52, 0.75) and reduced all-cause mortality (HR 0.63; 95% CI 0.41, 0.98). The most common adverse events were gastrointestinal and skin-related, and were generally mild to moderate in severity and infrequently led to discontinuation. Conclusions: These pooled analyses showed a favourable and persistent PFD treatment effect on FVC, PFS, and all-cause mortality through 72 weeks of follow-up. PFD was generally safe and well tolerated.