Continued Treatment with Nintedanib in Patients with Systemic Sclerosis-Associated Interstitial Lung Disease (SSc-ILD): Interim Analysis of SENSCIS-ON^[*]

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, with adverse events (AEs) that were manageable for most patients. SENSCIS (NCT02597933) was followed by an open-label extension trial, SENSCIS-ON (NCT03313180), to provide safety data, including data on FVC decline and AEs over the longer term.

Methods: Patients who completed the SENSCIS trial on treatment (NIN or placebo) and attended a follow-up visit 28 days later were eligible to participate in SENSCIS-ON, as well as female SSc-ILD patients who completed an open-label, drug–drug interaction study (DDIS) of NIN (for up to 28 days) plus ethinylestradiol and levonorgestrel (NCT03675581). In an interim analysis, we analyzed the change from baseline in FVC (mL) and AEs over 52 weeks in SENSCIS-ON, a) in patients who had received NIN in SENSCIS and continued NIN in SENSCIS-ON (“continued nintedanib” group), and b) in patients who had received placebo in SENSCIS and initiated NIN in SENSCIS-ON or who had received NIN in the DDIS (“initiated nintedanib” group). Analyses were pre-specified and descriptive.

Results: In 197 patients in the “continued nintedanib” and 247 patients (231 from SENSCIS, 16 from the DDIS) in the “initiated nintedanib” group, mean (SD) FVC at inclusion in SENSCIS-ON was 2379 (754) mL and 70.4 (18.1) % predicted and 2443 (814) mL and 70.8 (17.9) % predicted. Mean (SE) changes in FVC from baseline to week 52 of SENSCIS-ON were − 58.3 (15.5) mL in patients who continued and − 44.0 (16.2) mL in patients who initiated NIN ([Fig. 1]), and − 51.3 (11.2) mL in all patients treated in SENSCIS-ON, which is similar to the SENSCIS trial (− 42.7 [14.2] mL). Diarrhea was the most frequently reported AE ([Table 1]). AEs led to discontinuation of NIN in 9 patients (4.6%) who continued and 53 patients (21.5%) who initiated NIN. Elevations in alanine aminotransferase and/or aspartate aminotransferase to ≥ 3 times the upper limit of the normal range were reported in 3 patients (1.5%) who continued and 20 patients (8.1%) who initiated NIN.

Abb. 1 Change from baseline in FVC (mL) over time in SENSCIS-ON.

Tab. 1 Adverse events (reported irrespecitve of causality) over 52 weeks in SENSCIS-ON.

	Continued nintedanib (n = 197)	Initiated nintedanib (n = 247)
Any adverse event(s)	191 (97.0)	243 (98.4)
Most frequent adverse events*
Diarrhea	134 (68.0)	170 (68.8)
Nausea	32 (16.2)	60 (24.3)
Vomiting	27 (13.7)	53 (21.5)
Skin ulcer	36 (18.3)	43 (17.4)
Nasopharyngitis	28 (14.2)	33 (13.4)
Upper respiratory tract infection	27 (13.7)	26 (10.5)
Cough	24 (12.2)	21 (8.5)
Weight decreased	14 (7.1)	26 (10.5)
Abdominal pain	6 (3.0)	33 (13.4)
Serious adverse events**	42 (21.3)	60 (24.3)
Adverse event(s) leading to treatment discontinuation	9 (4.6)	53 (21.5)

Conclusion: The change in FVC in SENSCIS-ON was similar to the change observed in SENSCIS. The AE profile of NIN over longer-term use was consistent with that over 52 weeks in SENSCIS, supporting a clinically meaningful benefit of NIN in slowing the progression of SSc-ILD.

^* Presented at ACR 2020.

Publication History

Article published online:
30 April 2021