Nintedanib analyses support benefit in chronic fibrosing ILDs with progressive phenotype

New analyses of the INBUILD trial show nintedanib slowed lung function decline and reduced the annual rate of FVC decline in patients with a progressive form of chronic fibrosing interstitial lung diseases, including in various subgroups.

Healio previously reported results from the randomized, double-blind, placebo-controlled phase 3 INBUILD trial of 663 adults who, despite standard treatment during the previous 24 months, had progression of ILD (mean age, 65.8 years; 54% men; FVC was 69% of the predicted value). Patients were randomly assigned to nintedanib (Ofev, Boehringer Ingelheim) 150 mg twice day or placebo for 52 weeks. Results showed the adjusted rate of decline in FVC was significantly lower in the nintedanib group vs. placebo (–80.8 mL vs. –187.8 mL per year).

In a new prespecified analysis of the INBUILD trial, reported as an e-poster at the American Thoracic Society Virtual meeting, researchers assessed the effect of nintedanib on categorical changes in FVC to evaluate the proportion of patients with absolute and relative FVC declines of greater than 5% and greater than 10% predicted at 52 weeks, time to absolute FVC decline of at least 10% predicted, first investigator-reported acute ILD exacerbation or death.

Results showed that nintedanib slowed decline in lung function compared with placebo. Mean baseline FVC in the nintedanib group was 68.7% predicted compared with 69.3% predicted in the placebo group. At 52 weeks, 43.4% of patients assigned nintedanib had an absolute decline in FVC greater than 5% predicted compared with 55% of patients assigned placebo (OR = 0.63; 95% CI, 0.46-0.85). Similarly, 28.3% of patients assigned nintedanib had an absolute decline in FVC greater than 10% predicted at 52 weeks compared with 36.6% of those assigned placebo (OR = 0.68; 95% CI, 0.49-0.95).

Relative decline in FVC greater than 5% predicted was observed in 52.4% of patients assigned nintedanib compared with 68.6% assigned placebo (OR = 0.5; 95% CI, 0.36-0.68) and relative decline in FVC greater than 10% predicted was observed in 40.7% vs. 48.9%, respectively (OR = 0.7; 95% CI, 0.52-0.96).

In a separate prespecified subgroup analysis, researchers assessed the effect of nintedanib on the rate of FVC decline over 52 weeks in patient subgroups defined by baseline characteristics including sex, age, race, FVC and ILD diagnoses such as hypersensitivity pneumonitis, autoimmune ILDs, idiopathic nonspecific interstitial pneumonia, unclassifiable idiopathic interstitial pneumonia and other ILDs.

The analysis demonstrated that nintedanib reduced the annual rate of decline in FVC in patients with chronic fibrosing ILDs, irrespective of demographic characteristics, lung function or ILD diagnosis at baseline compared with placebo (P > .05).

“These results support the role of Ofev as a treatment for patients living with chronic fibrosing ILDs with worsening progression across varying demographic characteristics, lung function or diagnosis,” Martin Kolb, MD, PhD, professor in the division of respirology in the department of medicine at McMaster University in Ontario, Canada, said in the release.

Nintedanib is FDA approved to treat people with idiopathic pulmonary fibrosis, chronic ILD with a progressive phenotype and to slow the rate of decline in lung function in people with systemic sclerosis-associated ILD.

References:

• Cottin V, et al. Am J Respir Crit Care Med. 2020;201:A4556.
• Kolb MRJ, et al. Am J Respir Crit Care Med. 2020;201:A4555.
• Press Release.