Dose modifications and dose intensity during treatment with pirfenidone

Abstract

Background: During treatment of idiopathic pulmonary fibrosis with pirfenidone (PFD), gastrointestinal and skin-related adverse drug reactions (ADR) occurred in ∼30% of patients (pts). Temporary dose reductions and interruptions may allow pts to better manage side effects and continue PFD. Objective: To evaluate PFD reductions and interruptions in the Phase 3 CAPACITY and ASCEND trials. Methods: Pts (623 PFD 2403 mg/day, 624 placebo [PBO]) were followed over 52 weeks. Descriptive statistics and a linear slope analysis for annual rate of decline in forced vital capacity (FVC) by dose intensity were performed. Results: Mean daily dose was 2105 mg (median, 2300 mg). Dose reductions and interruptions occurred in 46% and 41% of PFD pts vs 29% and 25% of PBO pts, respectively. Median duration of reductions and interruptions for PFD pts were 28 and 14 days, respectively. Median time from start of PFD to first dose adjustment for common AEs was ∼95 days except for vomiting (28 days). Dose intensity of >90% was observed in 424/623 PFD and 559/624 PBO pts. The mean difference (±SEM) in annual rate of FVC decline between PFD and PBO over 52 weeks was 105.5±18.4 mL for dose intensity >90% (P Conclusions: While PFD dose adjustments may be required to manage ADRs, they tended to occur early and were limited in duration, allowing most pts to maintain efficacy and a high dose intensity.