No effect of baseline diffusing capacity of lung for carbon monoxide on benefit of nintedanib
23.Februar 2017 (online)
The two replicate, 52-week, Phase III INPULSIS® trials investigated the efficacy and safety of nintedanib 150 mg twice daily (bid) in patients with idiopathic pulmonary fibrosis. Inclusion criteria included a diffusing capacity of the lung for carbon monoxide (DLco) of 30 – 79% predicted. In both trials, nintedanib significantly reduced the annual rate of decline in forced vital capacity (FVC), the primary endpoint, versus placebo.
To assess the potential impact of DLco % predicted on the treatment effect of nintedanib.
Methods: Post-hoc analyses of patients with baseline DLco > 40% versus ≤40% predicted were conducted using pooled data from both INPULSIS® trials.
A total of 709 patients (nintedanib 428; placebo 281) had DLco > 40% predicted and 351 patients (nintedanib 210; placebo 141) had DLco ≤40% predicted. For patients with baseline DLco > 40% predicted, mean age was 66.4 years, 80.8% were male and mean FVC was 83.3% predicted. For patients with baseline DLco ≤40% predicted, mean age was 67.4 years, 76.4% were male and mean FVC was 72.1% predicted. In patients with baseline DLco > 40% predicted, the nintedanib versus placebo difference in adjusted annual rate of decline in FVC was 103.1 mL/year (95% CI: 63.6, 142.6); in patients with baseline DLco ≤40% predicted, it was 124.3 mL/year (95% CI: (56.2, 192.4). There was no significant treatment-by-time-by-subgroup interaction (p = 0.1468), indicating that the treatment effect of nintedanib was not different between the subgroups.
In a subgroup analysis of pooled data from the INPULSIS® trials, nintedanib slowed disease progression irrespective of the level of gas exchange impairment at baseline.
Presented at ERS 2016.