The Safety and Efficacy of Nintedanib in Systemic Sclerosis (SENSCIS) trial examined the use of nintedanib, a tyrosine kinase inhibitor, in patients with interstitial lung disease (ILD) associated with systemic sclerosis. In the study, these patients had a lower rate of decline in forced vital capacity than those treated with placebo. However, the study did not find the treatment resulted in clinical benefits for other manifestations of systemic sclerosis. The study by Oliver Distler, MD, professor of rheumatology at the University Hospital Zurich, Switzerland, and colleagues was published May 20 in the New England Journal of Medicine.1
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Researchers documented an adverse event profile similar to that seen in the INPULSIS trial of patients with idiopathic pulmonary fibrosis. That said, gastrointestinal adverse events, such as diarrhea, were not only more common in the SENSCIS patient population than in the idiopathic pulmonary fibrosis population, but also more common in nintedanib-treated patients than in placebo-treated patients.
The large (N=576), randomized, double-blind study included a broad range of patients with ILD-associated systemic sclerosis and extended for one year. Approximately half of the patients had diffuse cutaneous systemic sclerosis and half had limited cutaneous systemic sclerosis. The median time from the onset of the first non-Raynaud’s symptom was 3.4 years, and half of the patients were receiving mycophenolate at baseline.
During the study, patients received at least one dose of nintedanib or placebo, with 80.6% of nintedanib-treated patients and 89.2% of placebo-treated patients completing the 52-week intervention. The primary endpoint was the adjusted annual rate of change in forced vital capacity, which was -52.4 mL per year in the nintedanib group and -93.3 mL per year in the placebo group. The curves in the change from baseline in forced vital capacity separated by Week 12 and continued to diverge. When the investigators performed sensitivity analyses based on multiple imputation for missing data, they calculated P values for the primary endpoint ranging from 0.06 to 0.10.
At Week 52, researchers found no difference between the treatment and placebo groups for the Rodnan skin score, the St. George’s Respiratory Questionnaire (SGRQ), the absolute change from baseline in the score on the Health Assessment Questionnaire-Disability Index (HAQ-DI) or the absolute change from baseline in the Functional Assessment of Chronic Illness Therapy (FACIT)-Dyspnea score. Moreover, pre-specified subgroup analyses revealed the results for the key secondary endpoints did not differ significantly among the patients with different baseline characteristics.
The investigators found no differences between the two groups in the percentages of patients with any adverse event or serious adverse event. The most common adverse event was diarrhea, which was reported in 75.7% of nintedanib-treated patients and 31.6% of placebo-treated patients. Over the entire trial period, 10 nintedanib-treated patients and nine placebo-treated patients died. An uncontrolled, open-label extension study is ongoing.