Background/Purpose: In the SENSCIS trial in patients with systemic sclerosis-associated interstitial lung disease (SSc-ILD), nintedanib reduced the rate of decline in forced vital capacity (FVC) over 52 weeks compared with placebo (−52.4 versus −93.3 mL/year; difference 41.0 mL/year [95% CI 2.9, 79.0]; p=0.04), with adverse events that were manageable for most patients. Corticosteroids are commonly used in patients with SSc-ILD, despite a lack of evidence to support their efficacy. We assessed the efficacy and safety of nintedanib in patients who did and did not use corticosteroids in the SENSCIS trial.

Methods: Patients with SSc-ILD with ≥10% fibrosis of the lungs on HRCT were randomized to receive nintedanib 150 mg bid or placebo. Patients taking prednisone ≤10 mg/day or equivalent were allowed to participate. Lung function outcomes and adverse events (irrespective of causality) were analyzed in subgroups of patients who did and did not use corticosteroids. Corticosteroid use included use at baseline, during treatment with trial drug, and following discontinuation of trial drug (up to week 52).

Results: Of 576 patients who received trial drug, 206 (71.5%) and 191 (66.3%) patients in the nintedanib and placebo groups, respectively, used corticosteroids. Mean (SD) FVC (mL) at baseline was 2499 (814) in patients who used corticosteroids and 2501 (691) in patients who did not, and FVC % predicted was 71.9 (17.0) and 73.8 (15.9) in these groups respectively. In patients who received placebo, the mean (SE) rate of decline in FVC over 52 weeks was numerically greater in patients who used corticosteroids than in those who did not [-103.9 (16.7) versus -72.5 (23.3) mL/year]. Nintedanib reduced the annual rate of decline in FVC (mL/year) versus placebo both in patients who did and did not use corticosteroids, with no difference in the treatment effect between subgroups detected (treatment-by-time-by-subgroup interaction p=0.82) (Figure). In the nintedanib and placebo groups, respectively, absolute declines in FVC >5% predicted were seen in 22.4% and 27.2% of patients who used corticosteroids (OR 0.78 [95% CI: 0.49, 1.23]) and 15.9% and 30.9% of patients who did not use corticosteroids (OR 0.42 [95% CI: 0.20, 0.87]) (treatment-by-subgroup interaction p=0.16). The adverse event profile of nintedanib was similar between the subgroups by corticosteroid use, but the proportions of patients with nausea or vomiting adverse events were lower, and the proportion with upper respiratory tract infection was higher, in those who used corticosteroids (Table). The proportion of patients treated with nintedanib who had adverse events leading to discontinuation of study drug was similar in patients who did and did not use corticosteroids. A limitation of these analyses is that they have not been adjusted for differences between the subgroups of patients taking and not taking corticosteroids at baseline.

Conclusion: In the SENSCIS trial in patients with SSc-ILD, over two-thirds of patients used corticosteroids. Nintedanib reduced the annual rate of decline in FVC irrespective of use of corticosteroids. The adverse event profile of nintedanib was similar in patients who did and did not use corticosteroids.

« Back to 2019 ACR/ARP Annual Meeting

ACR Meeting Abstracts - https://acrabstracts.org/abstract/efficacy-and-safety-of-nintedanib-in-patients-with-systemic-sclerosis-associated-interstitial-lung-disease-subgroup-analysis-of-the-senscis-trial-by-corticosteroid-use/