Nintedanib slows lung function decline in SSc-associated interstitial lung disease
medwireNews: Findings from the SENSCIS trial indicate that the tyrosine kinase inhibitor nintedanib reduces the annual rate of decline in forced vital capacity (FVC) among patients with systemic sclerosis (SSc)-associated interstitial lung disease (ILD).
However, the researchers found no significant improvement in other clinical endpoints among patients treated with nintedanib versus placebo.
“Thus, while the results of the current trial suggest that nintedanib is effective in reducing the decline in FVC in patients with ILD associated with systemic sclerosis, this trial does not support nintedanib as a disease-modifying agent for systemic sclerosis as a whole,” write Oliver Distler (University Hospital Zurich, Switzerland) and colleagues.
As reported at the 2019 ATS International Conference in Dallas, Texas, USA, and published simultaneously in The New England Journal of Medicine, the phase III trial included 576 SSc patients with onset of the first non-Raynaud’s symptom within the previous 7 years and fibrosis affecting 10% or more of the lungs on a high-resolution computed tomography scan. Approximately half of the participants were receiving mycophenolate therapy at the time of study entry.
Distler and team demonstrated that the adjusted average rate of FVC decline was 52.4 mL/year for the 241 patients who were randomly assigned to receive nintedanib 150 mg twice daily and remained in the study at 1 year, compared with 93.3 mL/year for the 257 participants given placebo, a significant difference.
The researchers say that the rate of FVC decline, as well as the magnitude of the difference between the nintedanib and the placebo arm, “differed depending on mycophenolate use.”
Indeed, among patients receiving mycophenolate, FVC declined by an average of 40.2 mL/year in the nintedanib group versus 66.5 mL/year in the placebo group; the corresponding rates were 63.9 versus 119.3 mL/year for those who were not treated with mycophenolate.
Despite the beneficial effect on the primary endpoint of FVC decline, the SENSCIS (Safety and Efficacy of Nintedanib in Systemic Sclerosis) investigators note that “no other clinical benefit was observed” with nintedanib treatment.
For example, the adjusted average decrease in modified Rodnan skin score from baseline to 1 year was comparable in the nintedanib and placebo groups (2.17 and 1.96 points, respectively), as was the average change in St George’s Respiratory Questionnaire score (0.81 and –0.88 points, respectively), a measure of health-related quality of life.
The investigators report that a similar proportion of patients in the nintedanib and placebo groups experienced adverse events (98.3 vs 95.8%) and severe adverse events (18.1 vs 12.5%), but the rate of discontinuation due to adverse events was higher in the nintedanib group (16.0 vs 8.7%). The most frequently reported adverse event was diarrhea, affecting 75.7% of participants in the nintedanib group and 31.6% of those given placebo.
The researchers say that overall, the safety and adverse event profiles of nintedanib in the SENSCIS trial were “similar to profiles observed in the INPULSIS trials” of the agent in patients with idiopathic pulmonary fibrosis.
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