ATS 2023: Effects of Nintedanib on Circulating Biomarkers in Patients with Progressive Pulmonary Fibrosis: Subgroup Analyses of the INBUILD Trial
Rationale: The INBUILD trial investigated the effects of nintedanib on biomarkers of epithelial injury in subgroups of subjects with progressive fibrosing interstitial lung diseases (ILDs) other than idiopathic pulmonary fibrosis. The trial data suggested that nintedanib reduced circulating levels of these biomarkers compared to placebo. This study aimed to further evaluate the effects of nintedanib on biomarkers of epithelial injury in different ILD diagnosis subgroups using data from the INBUILD trial.
Methods: The study included individuals with diffuse fibrosing interstitial lung disease (ILD) of more than 10% extent on HRCT who showed progression of ILD within the previous 24 months despite standard treatment. Blood samples were obtained at the beginning of the study (baseline) and at subsequent intervals of 12, 24, 36, and 52 weeks. The study analyzed the fold changes in adjusted mean levels of circulating biomarkers at week 52 in five subgroups categorized by ILD diagnosis: hypersensitivity pneumonitis (HP), idiopathic non-specific interstitial pneumonia (iNSIP), unclassifiable idiopathic interstitial pneumonia (IIP), autoimmune disease-related ILDs, and other ILDs. The data underwent log10 transformation prior to analysis, and the estimates of change from baseline were then back-transformed. Interaction p-values were calculated to evaluate the potential variation in the effect of nintedanib compared to placebo among the subgroups without adjusting for multiple tests.
Results: A total of 663 subjects were included in the study, with 332 receiving nintedanib and 331 receiving placebo. Among these subjects, 173 (26.1%) had hypersensitivity pneumonitis (HP), 125 (18.9%) had non-specific interstitial pneumonia (NSIP), 114 (17.2%) had unclassifiable idiopathic interstitial pneumonia (IIP), 170 (25.6%) had autoimmune disease-related interstitial lung diseases (ILDs), and 81 (12.2%) had other ILDs. In the overall population, subjects treated with nintedanib showed significant reductions in fold changes from baseline in Krebs von den Lungen-6 (KL-6), surfactant protein D (SP-D), CA-125, and CA19-9 at week 52 compared to those who received placebo (ratio [95% CI]: 0.91 [0.84, 0.98] for KL-6, 0.91 [0.86, 0.97] for SP-D, 0.71 [0.66, 0.76] for CA-125, 0.88 [0.82, 0.95] for CA19-9). Subgroup analyses based on ILD diagnosis did not reveal any significant differences in the effects of nintedanib versus placebo on fold changes in these biomarkers (Figure).
Conclusions: The findings from the INBUILD trial indicate that nintedanib effectively decreased circulating levels of biomarkers associated with epithelial injury in individuals with progressive fibrosing interstitial lung diseases (ILDs), regardless of their specific ILD diagnosis.
American Thoracic Society (ATS) 2023 International Conference, 19th May–24th May, 2023, Washington, DC
