Background A higher score on the composite physiologic index (CPI), based on diffusing capacity of the lung for carbon monoxide (DLco) percent predicted, forced vital capacity (FVC) percent predicted and forced expiratory volume in 1 second (FEV1) percent predicted, is associated with worse prognosis in patients with ILDs. In the INBUILD trial in subjects with progressive fibrosing ILDs other than IPF, nintedanib reduced the annual rate of FVC decline by 57% versus placebo. We assessed the effect of nintedanib in subgroups by CPI at baseline. Methods We analysed, post hoc, the rate of decline in FVC and time to ILD progression (decline in FVC ≥10% predicted) or death over 52 weeks in subgroups by CPI at baseline (≤45 vs. >45), overall and in subjects with a usual interstitial pneumonia (UIP)-like fibrotic pattern on HRCT. Results Overall, 452/663 (68.2%) subjects had CPI >45 at baseline. In both the placebo and nintedanib groups, the rate of FVC decline was numerically greater in subjects with CPI >45 than ≤45 at baseline (Figure). The effect of nintedanib versus placebo on reducing the rate of FVC decline was similar between the subgroups by CPI, overall (interaction P=0.48) and in subjects with a UIP-like fibrotic pattern (interaction P=0.79). The proportions of patients who progressed or died (nintedanib vs. placebo) were: baseline CPI ≤45, 23.2% versus 34.2% (hazard ratio [HR] 0.65; 95% CI 0.38-1.13); baseline CPI >45, 26.6% versus 39.4% (HR 0.63; 95% CI 0.46-0.88). Among subjects with a UIP-like fibrotic pattern, these proportions were: baseline CPI ≤45, 22.6% versus 34.6% (HR 0.62; 95% CI 0.31-1.22); baseline CPI >45, 29.5% versus 43.0% (HR 0.63; 95% CI 0.42-0.94). Conclusions Data from INBUILD suggest that the effect of nintedanib on slowing the progression of fibrosing ILDs was consistent between subgroups based on CPI at baseline.