Nintedanib reduces lung function decline in systemic sclerosis-associated ILD

The SENSCIS trial, a randomised control trial studying the efficacy of nintedanib vs placebo on respiratory function among patients with interstitial lung disease mediated by systemic sclerosis (SSc-ILD), found a slower forced vital capacity (FVC) decline in patients treated with nintedanib [1,2].

Nintedanib is an intracellular tyrosine kinase inhibitor targeting the vascular endothelial growth factor receptor, the fibroblast growth factor receptor as well as the platelet-derived growth factor receptor. It is approved for the treatment of idiopathic pulmonary fibrosis and as a second-line combination option in some types of lung cancer. In the Safety and Efficacy of Nintedanib in Systemic Sclerosis (SENSCIS) trial, Prof. Oliver Distler (University Hospital Zurich, Switzerland) and colleagues sought to assess whether nintedanib could also be a safe and efficacious agent to treat SSc-ILD. SENSCIS is the largest randomised controlled trial conducted in patients with SSc-ILD, a disease for which there are currently no approved treatments. Primary results showed that nintedanib did slow the reduction in FVC rates over 1 year as compared with placebo.

SENSCIS was a double-blinded, multicentre, placebo-controlled, parallel-group trial that recruited 576 patients from 2015 to 2017 in 32 countries. Patients were randomised to receive either nintedanib (n=232) or placebo (n=257) in a 1:1 ratio administered in 150 mg doses twice daily. The primary endpoint was the annual rate of decline in FVC over a 52-week period. Secondary endpoints included changes in the modified Rodnan skin score and changes in the St. George’s Respiratory Questionnaire (SGRQ), which is used to evaluate skin fibrosis and respiratory status, respectively. Safety and spirometry measures were also assessed.

Patients randomised to the nintedanib group had a lower annual rate of change in FVC as compared with placebo at the 52-week mark, with divergence in rates noted after 12 weeks of treatment (-52.4 mL per year vs -93.3 mL per year; difference, 41.0 ml; 95% CI 2.9 to 79.0; P=0.04). The adjusted mean change in the modified Rodnan skin score at 52 weeks was -2.17 in the trial group and -1.96 in the placebo group (-0.21 difference; 95% CI -0.94 to 0.53). The change in SGRQ from baseline was 0.81 in the nintedanib group and -0.88 in the placebo group (95% CI -0.73 to 4.12). Adverse event rates were similar between groups and included diarrhoea, nausea, and elevations in aminotransferase levels.

Prof. Distler concluded: “The SENSCIS results provide positive news for people living with SSc-ILD and their physicians because currently there are no approved treatments. A 44% reduction in lung function decline indicates a significant slowdown in disease progression. Nintedanib could make a considerable difference to the lives of people with this rare and often life-threatening disease.”

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   1. Distler O, et al. A5963, ATS 2019, 17-22 May, Dallas, USA.
   2. Distler O, et al. N Engl J Med. 2019 May 20.

Posted on 23 July, 201929 February, 2024