Effects of nintedanib in patients with systemic sclerosis-associated ILD (SSc-ILD) and normal versus elevated C-reactive protein (CRP) at baseline: analyses from the SENSCIS trial

Background: In the SENSCIS trial in patients with SSc-ILD, nintedanib reduced the rate of FVC decline over 52 weeks. Elevated CRP is a marker of an inflammatory phenotype and associated with a greater rate of FVC decline and higher mortality in patients with SSc. Objective: To assess the effects of nintedanib in subgroups by CRP at baseline in SENSCIS. Methods: Patients with SSc-ILD with onset of first non-Raynaud symptom < 7 years and ≥ 10% lung fibrosis on HRCT were randomised to nintedanib or placebo. We analysed the rate of FVC decline (mL/year) over 52 weeks, the proportion of patients with an absolute increase in FVC ≥ 3% predicted (proposed MCID for FVC improvement in patients with SSc-ILD), and absolute change from baseline in mRSS at week 52 in normal vs. elevated high-sensitivity CRP (≤ 4.99 vs. > 4.99 mg/L) groups. Results: Of patients with available data 78/270 (28.9%) and 74/261 (28.4%) with nintedanib and placebo, had CRP > 4.99 mg/L at baseline. Compared with lower CRP, those with CRP > 4.99 mg/L included a similar proportion of ATA-positive patients (61.8% vs. 60.2%,), more with diffuse cutaneous SSc (63.2% vs. 49.3%), had a higher mean mRSS (13.7 vs. 10.2) and lower mean FVC % predicted (68.6% vs. 73.9%). The adjusted annual rate of FVC decline with placebo was numerically greater with CRP > 4.99 than ≤ 4.99 mg/L (− 106.6 [SE 27.6] vs. − 83.0 [17.1] mL/year). Nintedanib reduced the rate of FVC decline vs. placebo numerically more in patients with CRP > 4.99 than ≤ 4.99 mg/L but treatment-by-time-by-subgroup interaction p-value did not indicate nintedanib effect heterogeneity (p = 0.70) ([ Fig. 1 ]). The proportions of patients with an absolute increase in FVC ≥ 3% predicted were 20.4% and 15.0% in nintedanib and placebo with CRP ≤ 4.99 mg/L, 24.4% and 14.9% with CRP > 4.99 mg/L (treatment-by-subgroup interaction p = 0.59); mRSS adjusted mean changes − 2.2 (SE 0.3) and − 2.1 (0.3) with CRP ≤ 4.99 mg/L (difference − 0.1 [95% CI − 1.0, 0.8]), − 2.3 (0.5) and − 1.0 (0.5) with CRP > 4.99 mg/L (difference − 1.2 [− 2.7, 0.2]; treatment-by-visit-by-subgroup interaction p = 0.20). Abb. 1 Rate of decline in FVC (mL/year) over 52 weeks in subgroups by CRP at baseline in the SENSCIS trial. Conclusions: In the SENSCIS trial, the rate of FVC decline over 52 weeks in the placebo group was numerically greater in elevated CRP. Nintedanib reduced the rate of FVC decline both in patients with normal and elevated CRP, with a numerically greater effect in patients with elevated CRP. * Previously presented at ERS2020. Publication History Article published online: 30 April 2021 © 2021. Thieme. All rights reserved. Georg Thieme Verlag KG Rüdigerstraße 14, 70469 Stuttgart, Germany

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