Efficacy and Safety of Nintedanib in Patients with Systemic Sclerosis-Associated Interstitial Lung Disease: Subgroup Analysis of the SENSCIS Trial by Corticosteroid Use*

Background/purpose: Nintedanib reduced the rate of decline in 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) in the SENSCIS trial in SSC-ILD, with manageable adverse events (AEs). Corticosteroids (CS) are commonly used in SSc-ILD, despite a lack of evidence of efficacy. We assessed the efficacy and safety of nintedanib in patients who did/did not use CS in the SENSCIS trial.

Methods: Patients with SSc-ILD with ≥ 10% fibrosis of the lungs on HRCT were randomized to nintedanib 150 mg bid or placebo (prednisone ≤ 10 mg/day or equivalent were allowed). Lung function outcomes and AEs (irrespective of causality) were analyzed.

Results: Of 576 patients who received trial drug, 206 (71.5%) and 191 (66.3%) with nintedanib and placebo, respectively, used CS. Mean (SD) FVC (mL) at baseline was 2499 (814) in patients who used CS, 2501 (691) in patients who did not, and FVC % predicted was 71.9 (17.0) and 73.8 (15.9). With placebo, the mean (SE) rate of decline in FVC over 52 weeks was numerically greater in patients who used CS 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 in both groups (treatment-by-time-by-subgroup interaction p = 0.82) ([Fig. 1]). 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 CS (OR 0.78 [95% CI: 0.49, 1.23]) and 15.9% and 30.9% of patients who did not (OR 0.42 [95% CI: 0.20, 0.87]) (treatment-by-subgroup interaction p = 0.16). The AE profile of nintedanib was similar between the subgroups by CS use, but the proportions of patients with nausea or vomiting AEs were lower, and the proportion with upper respiratory tract infection was higher, in those who used CS ([Table 1]). The proportion of patients treated with nintedanib who had AEs leading to discontinuation of study drug was similar in patients who did and did not use CS (limitation of the analyses: no adjustment for differences in CS use at baseline).

Fig. 1 Annual rate of decline in FVC (mL/year) over 52 weeks in the SENSCIS trial in subgroups by use of corticosteroids.

Table 1 Adverse events by corticosteroid use in the SENSCIS trial.

	Used corticosteroids		Did not use corticosteroids
	Nintedanib (n = 206)	Placebo (n = 191)	Nintedanib (n = 82)	Placebo (n = 97)
Adverse events reported over 52 weeks (or until 28 days after last trial drug intake for patients who discontinued trial drug before week 52). Data are n (%) of patients with ≥ 1 such adverse event. Adverse events were coded according to preferred terms in the Medical Dictionary for Regulatory Activities (MedDRA). *Adverse events reported in > 10% of patients in any of the subgroups shown.
Most frequent adverse events*
Diarrhea	159 (77.2)	64 (33.5)	59 (72.0)	27 (27.8)
Nausea	59 (28.6)	27 (14.1)	32 (39.0)	12 (12.4)
Vomiting	45 (21.8)	21 (11.0)	26 (31.7)	9 (9.3)
Skin ulcer	42 (20.4)	38 (19.9)	11 (13.4)	12 (12.4)
Nasopharyngitis	27 (13.1)	33 (17.3)	9 (11.0)	16 (16.5)
Cough	27 (13.1)	35 (18.3)	7 (8.5)	17 (17.5)
Weight decreased	23 (11.2)	9 (4.7)	11 (13.4)	3 (3.1)
Upper respiratory tract infection	28 (13.6)	27 (14.1)	5 (6.1)	8 (8.2)
Abdominal pain	26 (12.6)	13 (6.8)	7 (8.5)	8 (8.2)
Fatigue	23 (11.2)	16 (8.4)	8 (9.8)	4 (4.1)
Decreased appetite	18 (8.7)	8 (4.2)	9 (11.0)	4 (4.1)
Adverse events leading to treatment discontinuation	31 (15.0)	15 (7.9)	15 (18.3)	10 (10.3)

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

* presented at ACR 2019