By Will Boggs MD
NEW YORK (Reuters Health) - 24/5/2019
Nintedanib, an intracellular inhibitor of tyrosine kinases, has been shown to reduce the rate of decline of FVC in patients with idiopathic pulmonary fibrosis, for which it is an approved treatment.
Idiopathic pulmonary fibrosis and ILD share some pathophysiological features, and nintedanib has shown beneficial effects in several animal models resembling aspects of systemic sclerosis and ILD associated with systemic sclerosis.
Dr. Oliver Distler from University Hospital Zurich, in Switzerland, and colleagues from 32 countries investigated the efficacy and safety of nintedanib in a randomized, placebo-controlled trial of 576 patients with ILD associated with systemic sclerosis.
The adjusted annual rate of change in FVC over 52 weeks, the primary endpoint, was significantly smaller in the nintedanib group (-52.4 mL versus -93.3 mL, P=0.04), the researchers report in the New England Journal of Medicine, online May 20. The paper was published to coincide with a presentation at the American Thoracic Society annual meeting in Dallas, Texas.
The curves for the change from baseline in SVC separated by week 12 and continued to diverge through week 52.
In contrast, changes in the modified Rodnan skin score, the St. George's Respiratory Questionnaire total score, the Health Assessment Questionnaire-Disability Index score and the Functional Assessment of Chronic Illness Therapy-Dyspnea score from baseline to week 52 did not differ significantly between the groups.
Adverse events and serious adverse events occurred with similar frequency in the nintedanib and placebo groups.
Mortality rates did not differ significantly between the nintedanib group (3.5%) and placebo group (3.1%).
"The results of the SENSCIS trial showed that nintedanib has a beneficial effect by reducing the rate of decline in FVC in patients with ILD associated with systemic sclerosis over a 1-year period," the researchers conclude. "In this trial, no other clinical benefit was observed."
"An uncontrolled open-label extension study is ongoing and will provide long-term data on nintedanib therapy in patients with ILD associated with systemic sclerosis," they note.
Dr. Maurizio Cutolo of the University of Genova, in Italy, who contributed to the formulation of European League Against Rheumatism (EULAR) recommendations for the treatment of systemic sclerosis, told Reuters Health by email, "The SENSCIS results (offer hope) for systemic sclerosis-interstitial lung disease (SSc-ILD) patients, as currently there are no approved treatments. A 44% reduction in lung-function decline indicates an unforeseen (compared with previous tested compounds) reduction in disease progression."
"Very recent studies from our lab that will be presented during the next EULAR Congress in Madrid and testing the in vitro effects of nintedanib on circulating fibrocytes and resident skin fibroblasts from the same systemic sclerosis patients, further support the molecular mechanisms, the important antifibrotic activity of this tyrosine kinases inhibitor," he said.
Boehringer Ingelheim sponsored the trial and employed several of the authors.
Dr. Distler did not respond to a request for comments.
N Engl J Med 2019