Nintedanib reduces ILD progression irrespective of underlying diagnosis
Treatment with nintedanib slowed the rate of interstitial lung disease progression in patients with chronic fibrosing ILD and progressive phenotype, irrespective of their underlying ILD diagnosis, according to analysis of the INBUILD trial.
“The study evaluated nintedanib antifibrotic therapy in a large group of patients with progressive fibrosis despite historical management considered appropriate by real-world clinicians,” Athol U. Wells, MD, professor at the National Institute for Health Research Respiratory Biomedical Research Unit at Royal Brompton and Harefield NHS Foundation Trust in London, told Healio. “In a variety of pulmonary disorders, there was a remarkably uniform effect across the five major subgroups, indicating that this antifibrotic agent is active on pathways that are common to progressive fibrosing lung diseases.”
The randomized, double-blind, placebo-controlled, phase 3 INBUILD trial investigated the safety and efficacy of nintedanib (Ofev, Boehringer Ingelheim) in adults with progressive fibrosing ILD other than idiopathic pulmonary fibrosis. A total of 663 patients were randomly assigned to nintedanib 150 mg twice daily or placebo for 52 weeks.
Healio previously reported primary results of the INBUILD trial. At 52 weeks, the primary endpoint of adjusted rate of decline in FVC was significantly lower in the nintedanib group (–80.8 mL per year vs. –187.8 mL per year with placebo; between group difference, 107 mL; 95% CI, 65.4-148.5).
For the subgroup analysis, researchers evaluated the rate of FVC decline over 52 weeks in five prespecified subgroups recruited from February 2017 to April 2018.
Among the 663 participants who received at least one dose of nintedanib or placebo, 26% had a diagnosis of chronic hypersensitivity pneumonitis, 26% had an autoimmune ILD, 19% had idiopathic nonspecific interstitial pneumonia, 17% had unclassifiable idiopathic interstitial pneumonia and 12% had other ILDs.
The effect of nintedanib on reduction of the rate of FVC decline was consistent among the five subgroups, at 73.1 mL per year (95% CI, –8.6 to 154.8) in patients with hypersensitivity pneumonitis, 104 mL per year (95% CI, 21.1-186.9) in patients with autoimmune ILDs, 141.6 mL per year (95% CI, 46-237.2) in patients with idiopathic nonspecific interstitial pneumonia, 68.3 mL per year (95% CI, –31.4 to 168.1) in patients with unclassifiable idiopathic interstitial pneumonia and 197.1 mL per year (95% CI, 77.6-316.7) in patients with other ILDs (P = .41 for treatment by subgroup by time interaction), according to the results.
Adverse events in these five subgroups were similar to those observed in the overall population, according to the researchers.
“ILD physicians now have an effective new treatment approach that is applicable to the large subgroup of patients with non-IPF disorders that progress and die because current therapies are ineffective,” Wells said. “The amplitude of the treatment effect on FVC decline is at least the equal of treatment effects in any large study in the field of fibrosing lung disease.”
Moving forward, Wells suggested further research on longer-term benefits of antifibrotic therapy, a more accurate real-world definition of chronic progression of lung fibrosis, pathogenetic studies to identify pathways common to progressive fibrosis and studies identifying features that accurately identify the subset of patients that will progress despite use of traditional immunosuppressive agents.
For more information:
Athol U. Wells, MD, can be reached at rbhild@rbht.nhs.uk.