Quartile forced vital capacity changes at 3, 6, 9 and 12 months with pirfenidone in patients with Idiopathic Pulmonary Fibrosis: a pooled phase III analysis

Rationale:

Idiopathic pulmonary fibrosis (IPF) is an unpredictable lung disease characterized by a progressive loss of lung function. The antifibrotic drug, pirfenidone, has been evaluated in three multinational, Phase III trials in patients with IPF. We performed pooled analyses of forced vital capacity (FVC) outcomes (% predicted FVC and FVC volume) over 12 months from these trials, with particular attention to the treatment effect of pirfenidone compared with placebo on quartile changes from baseline.

Methods:

Source data were from patients who were randomized to receive pirfenidone 2403 mg/day or placebo in CAPACITY 004 (NCT00287716), CAPACITY 006 (NCT00287729), or ASCEND (NCT01366209). Absolute changes from baseline in % predicted FVC and relative changes from baseline in FVC volume were analyzed every 3 months for 12 months using a rank analysis of covariance model. Patients with missing data due to death were ranked worse than those who remained alive (earlier deaths had worse ranks); missing values for any other reason were imputed using the sum of squared differences method. Upper and lower quartile summary statistics were estimated within each treatment group at each time point.

Results:

The analyses included 1247 patients (pirfenidone, N = 623; placebo, N = 624). At baseline, patients receiving pirfenidone and placebo had similar median % predicted FVC (71.1% and 70.3%, respectively) and median FVC volume (2720 mL and 2748 mL, respectively). For both % predicted FVC (shown in the Figure) and FVC volume, the lower quartile and upper quartile changes from baseline were all consistently in favor of pirfenidone at every time point studied (p < 0.0001). At Month 12, absolute treatment differences (pirfenidone – placebo) for % predicted FVC were 2.2% (upper quartile) and 3.2 % (lower quartile), and for FVC volume were 80 mL (upper quartile) and 130 mL (lower quartile), each in favor of pirfenidone.

Fig. 1: Quartile % predicted FYC changes from baseline over 12 months

Conclusions:

These pooled analyses demonstrate that patients treated with pirfenidone in Phase III trials had consistently better quartile FVC outcomes at Months 3, 6, 9, and 12 compared with patients who received placebo.

Funding source:

This study was sponsored by Genentech, Inc. and F. Hoffmann-La Roche Ltd.