Pooled analysis of mortality data from the TOMORROW and INPULSIS™ trials of nintedanib in idiopathic pulmonary fibrosis (IPF)

Background: Nintedanib has been investigated as a treatment for IPF in three randomized, placebo-controlled, 52-week trials: the Phase 2 TOMORROW trial and the two replicate Phase 3 INPULSIS™ trials. Compared with placebo, nintedanib 150 mg twice daily reduced the decline in forced vital capacity (FVC), consistent with a slowing of disease progression. Mortality was a secondary endpoint in all three trials; however, the trials were not powered to show a between-group difference. Our aim was to obtain a more precise estimate of the effect of nintedanib 150 mg twice daily on mortality using pooled data from the TOMORROW and INPULSIS™ trials.

Methods: A blinded adjudication committee ascertained the primary cause of deaths. All-cause and respiratory mortality over 52 weeks, measured as time to death, were analyzed using data from patients treated with nintedanib or placebo using a log rank test and Cox model.

Results: In the pooled dataset, 723 patients were treated with nintedanib and 508 with placebo. The proportion of patients who died from any cause over 52 weeks was 5.8% in the nintedanib group and 8.3% in the placebo group (HR 0.70 [95% CI: 0.46, 1.08]; p = 0.0955). Respiratory mortality over 52 weeks was 3.6% in the nintedanib group and 5.7% in the placebo group (HR 0.62 [95% CI: 0.37, 1.06]; p = 0.0779).

Conclusion: The pooled analysis of data from the TOMORROW and INPULSIS™ trials shows a trend toward a reduction in mortality in patients treated with nintedanib.

Clinical implications: These findings reflect the consistent effect of nintedanib on slowing disease progression in patients with IPF.

Presented at ICLAF 2014