Changes in Imaging Markers in Patients with Systemic Sclerosis-Associated Interstitial Lung Disease (SSc-ILD) Treated with Nintedanib: Sub-Study of the SENSCIS Trial^[*]

Introduction: In the SENSCIS trial with SSc-ILD, nintedanib (NIN) reduced the rate of decline in FVC (mL/year) over 52 weeks by 44% vs. placebo. The effects of NIN on markers of lung damage on HRCT were assessed in a sub-study.

Methods: Patients in SENSCIS had SSc with onset of first non-Raynaud symptom ≤ 7 years before screening and fibrotic lung ILD ≥ 10% on HRCT. Patients were randomized to NIN or placebo. HRCT images were assessed at baseline and at week 52 or 60. Changes from baseline in abnormalities (honeycombing and/or reticulation and/or ground-glass opacity) in both lungs were categorized by two radiologists as “much better”, “better”, “same”, “worse”, “much worse” or “unknown”. “Intermediate better” or “intermediate worse” were considered where there was disagreement between the radiologists in “much better”/“better” and “worse”/“much worse”. Where there was disagreement in other categorizations, a third radiologist adjudicated. An ordinal logistic regression analysis (proportional odds model) adjusted for anti-topoisomerase antibody I was used to compare changes between the treatment groups. Changes in a quantitative fibrosis score, a measure of the extent (%) of reticular patterns with architectural distortion, were assessed using data-driven texture analysis. Analyses were conducted in patients with trial medication ≥ week 24 and HRCT scan at week 52/60.

Results: 150 of 576 patients in SENSCIS participated (NIN 73, placebo 77). The rate of decline in FVC over 52 weeks was similar in the overall and the sub-study population ([Fig. 1]). Compared with placebo (n = 59), a lower proportion of NIN patients (n = 52) had a worsening in qualitative parameters (40.4% vs. 45.8%) (Table). Ordinal logistic regression analysis demonstrated a numerically greater risk of worsening with placebo compared with NIN (OR 1.24 [95% CI: 0.63, 2.47]; p = 0.53). Adjusted mean (SE) changes from baseline in quantitative fibrosis score were 2.50 (0.88) % with NIN (n = 23) and 2.80 (0.73) % with placebo (n = 31) (difference: − 0.31% [95% CI: − 2.36, 1.75]; p = 0.77).

Abb. 1 Rate of decline in FVC (mL/year) over 52 weeks in the overall SENSCIS trial population and in the HRCT sub-study.

Conclusion: In the sub-study, qualitative and quantitative changes on HRCT over 52 – 60 weeks were small. Numerical but non-significant trends towards less worsening were observed with NIN vs. placebo (analyses were limited by the small number of patients with evaluable HRCT scan).

Tab. 1 Changes from baseline in the extent of regions with evidence of abnormalities (honeycombing and/or reticulation and/or ground-glass opacity) based on qualitative HRCT review.

	Nintedanib (n = 52)	Placebo (n = 59)
Much better	0	0
Intermediate better	2 (3.8)	1 (1.7)
Better	7 (13.5)	8 (13.6)
Same	22 (42.3)	23 (39.0)
Worse	15 (28.8)	17 (28.8)
Intermediate worse	3 (5.8)	6 (10.2)
Much worse	3 (5.8)	4 (6.8)

^* Previously presented at ACR 2020

Publication History

Article published online:
30 April 2021