Effect of continued treatment with pirfenidone following clinically meaningful declines in forced vital capacity: analysis of data from three phase 3 trials in patients with idiopathic pulmonary fibrosis

Abstract

Background: The assessment of treatment response in idiopathic pulmonary fibrosis (IPF) is complicated by the variable clinical course. We examined the variability in the rate of disease progression and evaluated the effect of continued treatment with pirfenidone in patients who experienced meaningful progression during treatment.

Methods: The source population included patients enrolled in the ASCEND and CAPACITY trials (N=1247). Pearson's correlation coefficients were used to characterise the relationship between changes in FVC during consecutive 6-month intervals in the placebo population. Outcomes following a ≥10% decline in FVC were evaluated by comparing the proportion of patients in the pirfenidone and placebo groups who experienced a ≥10% decline in FVC or death during the subsequent 6 months.

Results: A weak negative correlation was observed between FVC changes during consecutive intervals in the placebo population (coefficient, -0.146, p<0.001), indicating substantial variability. Thirty-four (5.5%) and 68 (10.9%) patients in the pirfenidone and placebo groups, respectively, experienced a ≥10% decline in FVC by month 6. During the subsequent 6 months, fewer patients in the pirfenidone group compared with placebo experienced a ≥10% decline in FVC or death (5.9% vs 27.9%; relative difference, 78.9%). There was one (2.9%) death in the pirfenidone group and 14 (20.6%) deaths in the placebo group (relative difference, 85.7%).

Conclusions: Longitudinal FVC data from patients with IPF showed substantial intrasubject variability, underscoring the inability to reliably assess therapeutic response using serial FVC trends. In patients who progressed during treatment, continued treatment with pirfenidone resulted in a lower risk of subsequent FVC decline or death.

Trial registration numbers: NCT01366209, NCT00287729, NCT00287716.

Keywords: Idiopathic pulmonary fibrosis.

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Figures

Figure 1

Study profile. (A) Assessment of FVC variability. (B) Assessment of treatment outcomes following a ≥10% absolute decline in FVC.

Figure 2

Relationship between changes in per cent predicted FVC during two consecutive 6-month intervals*. *Pooled placebo population, CAPACITY and ASCEND studies (N=540).

Figure 3

Spaghetti plot of change from baseline to 1 year in per cent predicted FVC*. *Randomly selected patients from the pooled placebo population from the CAPACITY and ASCEND studies (N=50).

Figure 4

Median change in per cent predicted FVC during the 6-month period following an initial decline in FVC ≥10%. *Rank analysis of covariance with ranked change from baseline as the outcome variable; study, treatment, and region as fixed effects; and ranked baseline FVC as a covariate. Deaths are ranked worst according to time until death.