6 Minute Walk Distance (6MWD) And Forced Vital Capacity (FVC) In patients with Idiopathic Pulmonary Fibrosis (IPF): Similar pattern of pirfenidone response

Rationale: Pirfenidone is an oral molecule with dual anti-fibrotic and anti-inflammatory properties. The CAPACITY trials were two nearly identical randomized, double-blind, placebo controlled studies evaluating the safety and efficacy of pirfenidone in patients with IPF. To further assess patterns of response to pirfenidone across %FVC and 6MWD, two very different and important clinical outcome measures, we compared serial changes in these outcomes and assessed the intra-patient correlations in pooled data from both trials. Methods: The study design for the CAPACITY trials has been described elsewhere. In the present analysis, percent predicted FVC and 6MWD were assessed in the pooled pirfenidone 2403 mg/day (n=345) and placebo (n=347) groups at baseline and at 12-week intervals until Week 72. The relationship between changes in percent predicted FVC and 6MWD at Week 72 in individual patients was assessed by product-moment correlation. Results: The pattern of change over time in %FVC and 6MWD in both pirfenidone-treated and placebo patients was very similar (Figure 1). For both outcome measures, the treatment effect was evident at week 12, reached a peak at week 36, and persisted through Week 72. While the temporal pattern of change was similar in both pirfenidone-treated and placebo patients, the correlation in change at Week 72 across these two measures in individual patients was weak (r2 = 0.10 for both the pirfenidone 2403 mg/day and placebo groups). Conclusions: The important clinical outcome measures of change in %FVC and 6MWD appear to have similar responsiveness characteristics based on temporal changes and a similar pirfenidone treatment effect. The weak correlation of change within individual patients suggests these outcomes are measuring different functional domains of the IPF disease process. Figure 1. Change from Baseline in Percent Predicted FVC and 6MWT Distance (Figure presented).