Nintedanib slows FVC decline in autoimmune-related interstitial lung disease
Click Here to Manage Email Alerts
Nintedanib slows the rate of forced vital capacity decline in patients with fibrosing autoimmune disease-related interstitial lung disease, with adverse events manageable for most, according to data published in Arthritis & Rheumatology.
“A substantial proportion of patients with systemic autoimmune disease, such as rheumatoid arthritis, dermatomyositis and polymyositis, scleroderma, Sjogren’s syndrome and others, develop various forms of lung involvement that have profound effects on their quality of life and life expectancy,” Eric L. Matteson, MD, of the Mayo Clinic College of Medicine and Science, in Rochester, Minnesota, told Healio. “There is a direct correlation between quality of life and survivorship, and the extent of fibrosis on imaging and loss of pulmonary function.
“Recently, antifibrotic therapies have become available for the management of progressive lung fibrosis,” he added. “However, it has not been clear if antifibrotic therapy might also lessen the rate of decline in lung function among patients with progressive autoimmune disease-related interstitial lung disease, for whom good treatment options have not been available.”
To examine the efficacy and safety of nintedanib (Ofev, Boehringer Ingelheim) in patients with progressive fibrosing ILDs related to autoimmune disease, Matteson and colleagues analyzed data from the INBUILD trial. According to the researchers INBUILD was a randomized, double-blind, placebo-controlled study conducted across 15 countries in 663 patients with ILDs other than idiopathic pulmonary fibrosis. Additional eligibility criteria included diffuse fibrosing lung disease of greater than 10% on HRCT, predicted FVC of 45% or greater and diffusing capacity for carbon monoxide from 30% to less than 80% predicted.
Participants were also required to exhibit ILD progression within 24 months prior to screening despite treatment. Patients receiving azathioprine, cyclosporine, mycophenolate mofetil, tacrolimus (Prograf, Astellas Pharma), rituximab (Rituxan, Genentech), cyclophosphamide or more than 20 mg of oral glucocorticoids per day were excluded.
Participants were randomly assigned to receive either 150 mg of nintedanib twice daily or a placebo. After 52 weeks of treatment, participants entered a variable period in which they continued to receive blinded treatment until all had completed the trial.
For this analysis, Matteson and colleagues presented data from the 170 participants with ILD related to autoimmune disease.
According to the researchers, the rate of FVC decline over 52 weeks was –75.9 mL per year in the nintedanib group, compared with –178.6 mL per year among those who received a placebo (difference = 102.7; 95% CI, 23.2-182.2). Additionally, the researchers found no heterogeneity in the effect of nintedanib, compared with placebo, across subgroups by ILD diagnosis (P = .91).
The most frequent adverse event was diarrhea, reported in 63.4% of those treated with nintedanib and in 27.3% of the placebo group. Adverse events led to permanent treatment discontinuation in 17.1% and 10.2% of participants in the nintedanib and placebo groups, respectively.
“We found that nintedanib significantly reduced the rate of decline in forced vial capacity by 58%, and that the effects were very similar to what was seen in subjects who had pulmonary fibrosis not related to an underlying autoimmune disease,” Matteson said. “The frequency of the known side effect of diarrhea was similar in subjects with and without underlying autoimmune disease. The results demonstrate that nintedanib significantly slows the rate of decline in pulmonary function in autoimmune disease-related ILD, a finding that can aid in the management of this complex disease manifestation.”
Collapse
Click Here to Manage Email Alerts