Effect of FEV1/FVC ratio on reduction in FVC decline with nintedanib in the INPULSIS™ trials
Background: The two replicate randomized, placebo-controlled, 52-week Phase III INPULSIS™ trials assessed the efficacy and safety of nintedanib 150 mg twice daily in patients with IPF. Patients with an FEV1/FVC ratio of < 0.7 were excluded. Compared with placebo, nintedanib slowed disease progression by significantly reducing the annual rate of decline in forced vital capacity (FVC), the primary endpoint, in both trials.
Methods: A post-hoc subgroup analysis of the effect of nintedanib on the primary endpoint in patients with a baseline FEV1/FVC ratio of > 0.8 versus ≤0.8 was conducted using pooled data from both trials.
Results: 649 patients (401 nintedanib, 248 placebo) had a baseline FEV1/FVC ratio of > 0.8 and 412 patients (237 nintedanib, 175 placebo) had a ratio of ≤0.8. Baseline characteristics in patients with an FEV1/FVC ratio of > 0.8 and ≤0.8 were as follows: mean age 66.4 and 67.3 years, 74.1% and 87.4% were male, mean FVC % predicted 75.7% and 85.6%, respectively. In patients with a baseline FEV1/FVC ratio of > 0.8, the adjusted annual rate of decline in FVC was -128.1 mL/year with nintedanib and -254.2 mL/year with placebo (difference: 126.1 mL/year [95% CI: 81.6, 170.6]) while in patients with a baseline FEV1/FVC ratio of ≤0.8 it was -88.6 mL/year with nintedanib and -184.0 mL/year with placebo (difference: 95.5 mL/year [95% CI: 41.9, 149.1]).
Conclusion: Nintedanib slowed disease progression by significantly reducing the rate of FVC decline both in patients with an FEV1/FVC ratio of > 0.8 and patients with an FEV1/FVC ratio of ≤0.8.
Presented at ICLAF 2014