LAUSR

Background: In the Phase III INPULSIS ® trials, nintedanib 150 mg twice daily slowed disease progression in patients with IPF by significantly reducing the annual rate of decline in FVC. Patients with FVC ≥50% predicted, DLco 30–79% predicted and FEV 1 /FVC ≥0.7 were eligible for inclusion. The CPI, calculated based on percent predicted values for FVC, DLco and FEV 1 , is a measure of the extent of pulmonary fibrosis in patients with IPF. Aim: To assess the effect of nintedanib on change in CPI. Methods: The measures required to calculate CPI were taken at baseline, week 24 and week 52. Post-hoc analyses were conducted on the effect of nintedanib on change from baseline in CPI at weeks 24 and 52 using pooled data from both INPULSIS ® trials. Adjusted mean difference versus placebo at week 52 was assessed based on a mixed model for repeated measures (MMRM). Results: 1061 patients were treated in the INPULSIS ® trials (638 with nintedanib, 423 with placebo). Mean (SD) CPI at baseline was 45.9 (10.9) and 46.3 (11.0) in the nintedanib and placebo groups, respectively. At week 24, mean (SD) changes from baseline in CPI were 2.1 (8.3) in the nintedanib group and 2.2 (7.0) in the placebo group. Based on MMRM, the adjusted mean (SE) change from baseline in CPI at week 52 was 2.8 (0.4) in the nintedanib group and 3.9 (0.5) in the placebo group (difference −1.1 [95% CI: −2.3, 0.1]; p=0.0676). Conclusion: Based on data from the INPULSIS ® trials, nintedanib was associated with a marginal treatment effect on change from baseline in CPI at week 52. This may be due to the high variability in DLco assessments in multi-centre clinical trials and the influence of factors other than extent of fribrosis on DLco.