Effect of baseline composite physiologic index on benefit of nintedanib in IPF

Background: The replicate, 52-week, randomised, placebo-controlled Phase III INPULSIS^® trials investigated the effect of nintedanib 150 mg twice daily in patients with idiopathic pulmonary fibrosis. Nintedanib significantly reduced the annual rate of decline in forced vital capacity (FVC) in both trials. The composite physiologic index (CPI) may more accurately reflect the extent of pulmonary fibrosis than individual lung function tests, which may be confounded by coexisting emphysema. Aim: To assess the potential impact of CPI on the effect of nintedanib on FVC decline. Methods:Post-hoc analyses of patients with baseline CPI ≤45 vs >45 and ≤55 vs >55 were conducted using pooled data from both INPULSIS^® trials. Results: Mean (SD) baseline CPI was 46.1 (10.9). In total, 462 patients (nintedanib 278; placebo 184) had CPI ≤45 and 598 (nintedanib 360; placebo 238) had CPI >45; 829 patients (nintedanib 509; placebo 320) had CPI ≤55 and 231 (nintedanib 129; placebo 102) had CPI >55. The annual rate of FVC decline with nintedanib and placebo, respectively, was −108.4 and −209.9 mL/year in patients with baseline CPI ≤45 and −118.8 and −235.2 mL/year in patients with CPI >45. The effect of nintedanib was similar in these subgroups; nintedanib vs placebo differences in annual rate of decline in FVC were 101.5 mL/year (95% CI: 51.4, 151.6) and 116.4 mL/year (95% CI: 69.3, 163.5), respectively (treatment-by-subgroup interaction p=0.6646). The treatment effect of nintedanib was of a similar absolute magnitude if a baseline CPI threshold of 55 was used to define subgroups. Conclusion: In subgroup analyses of pooled data from the INPULSIS^® trials, nintedanib slowed disease progression irrespective of baseline CPI.