The SENSCIS trial: nintedanib slows declines in FVC in patients with interstitial lung disease caused by systemic sclerosis

1. The SENSCIS trial, a randomized control trial studying the efficacy of nintedanib, an intracellular tyrosine kinase inhibitor, versus placebo on respiratory function among patients with interstitial lung disease mediated by systemic sclerosis, found a slower forced vital capacity (FVC) decline in patients treated with nintedanib.

2. There were no other clinical benefits derived for other manifestations of systemic sclerosis.

Evidence Rating Level: 1 (Excellent)  

Study Rundown: Systemic sclerosis, an autoimmune condition that affects multiorgan systems, can often lead to interstitial lung disease or fibrosis of the lung parenchyma. This disease is often treated with immunosuppressants such as mycophenolate or cyclophosphamide. A novel agent, nintedanib, is an intracellular tyrosine kinase inhibitor approved for the treatment of idiopathic pulmonary fibrosis. In the Safety and Efficacy of Nintedanib in Systemic Sclerosis (SENSCIS) trial, researchers sought to assess whether nintedanib could also be a safe and efficacious agent to treat interstitial lung disease associated with systemic sclerosis. Primary results showed that nintedanib did slow the reduction in FVC rates over one year as compared to placebo.

More research is warranted to further investigate whether nintedanib could be a viable therapeutic adjunct for respiratory illness caused by systemic sclerosis. A study strength included evaluation of multiple secondary endpoints.

Click to read the study in NEJM

Relevant Reading: Efficacy of a tyrosine kinase inhibitor in idiopathic pulmonary fibrosis

In-Depth [randomized controlled trial]:  This trial was a double-blinded, multicenter, placebo-controlled, parallel-group trial that recruited 576 patients between 2015 to 2017. Patients were randomized to receive either nintedanib (n=232) or placebo (n=257) in a 1:1 ratio administered in 150mg doses twice daily. The primary end point 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 randomized to the nintedanib group had a lower annual rate of change in FVC as compared to placebo when assessed 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% confidence interval [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 diarrhea, nausea and elevations in aminotransferase levels.

Image: PD

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