Effect of nintedanib on progression of systemic sclerosis-associated interstitial lung disease (SSc-ILD) beyond 52 weeks: data from the SENSCIS trial^[*]

Rationale: In the SENSCIS trial, patients with SSc-ILD were randomized to nintedanib (NIN) or placebo until the last patient reached week 52 but for no longer than 100 weeks. Patients who prematurely discontinued treatment were asked to attend visits up to week 100 or the end of the trial. NIN reduced the FVC decline over 52 weeks versus placebo (− 52.4 vs. − 93.3 mL/year; difference 41.0 mL/year [95% CI 2.9, 79.0]). We investigated the effect of NIN on FVC decline over the whole trial.

Methods: The FVC decline (mL/year) over up to 100 weeks was assessed using three approaches. Firstly: all available data, including data collected post-treatment discontinuation. Secondly: post-treatment data only from patients who prematurely discontinued treatment. Thirdly: only on-treatment data (measurements taken between randomization and date of last trial drug intake or week 100, whichever occurred first) to explore the expected effect of NIN in patients who remained on treatment. Between-group differences in FVC (mL) at week 100 were estimated. We assessed time to relative decline in FVC (mL) > 5% and > 10% over 100 weeks. Safety was assessed based on adverse events reported up to the last drug intake plus 28 days. Analyses were descriptive.

Results: At baseline, mean (SD) FVC was 2459 (736) mL in the NIN group (n = 288) and 2541 (816) mL in the placebo group (n = 288). Median exposure to study drug over the whole trial was 15.4 and 15.6 months in the NIN and placebo groups, respectively. The adjusted mean (SE) annual rates of FVC decline over 100 weeks based on the three approaches are presented in [Table 1]. Over 100 weeks, in the NIN and placebo groups, respectively, a relative decline in FVC (mL) > 5% occurred in 59.4% and 69.8% of patients (HR 0.80 [95% CI: 0.65, 0.99]; p = 0.04) and a relative decline in FVC (mL) > 10% occurred in 35.8% and 40.6% of patients (HR 0.88 [95% CI: 0.67, 1.14]; p = 0.33). Adverse events leading to permanent discontinuation of study drug were reported in 17.4% and 10.1% of patients treated with NIN and placebo, respectively.

Tab. 1 

	Adjusted mean (SE) rate of decline in FVC over 100 weeks (mL/year)		Between-group difference in adjusted mean rate of decline in FVC over 100 weeks (mL/year) (95% CI)	Estimated between-group difference in FVC at week 100 (mL)
	Nintedanib	Placebo
Including all available data	− 62.3 (10.7)	− 86.0 (10.5)	23.7 (− 5,8, 53.2)	45.6
Including post-treatment data only from patients who prematurely discontinued treatment	− 54.9 (11.1)	− 88.8 (10.9)	34.0 (3.4, 64.5)	65.3
Inlcuding on-treatment data only*	− 55.1 (12.3)	− 94.0 (11.7)	38.9 (5.6, 72.1)	74.7

Conclusions: Collectively, data from the SENSCIS trial suggest that the effect of NIN on slowing the progression of SSc-ILD persists beyond 52 weeks. The adverse event profile of NIN over the whole trial (up to 100 weeks) was consistent with that reported over 52 weeks.

^* Presented at ATS2020.

Publication History

Article published online:
30 April 2021