Dose adjustments in the SENSCIS trial of nintedanib in patients with systemic sclerosis-associated ILD (SSc-ILD)

Abstract

Background: In the SENSCIS trial, nintedanib reduced the progression of SSc-ILD vs placebo, with an adverse event (AE) profile comparable to IPF.

Aim: To evaluate dose adjustments used in the SENSCIS trial to manage AEs.

Methods: Patients with SSc-ILD were randomised to receive nintedanib 150 mg bid or placebo. Dose reductions to 100 mg bid and treatment interruptions were allowed.

Results: 576 patients were treated (288 per group). Over 52 weeks, the proportion of patients with dose intensity (amount of drug administered divided by amount that would have been received had 150 mg bid been administered over 52 weeks) >90% was 63.5% with nintedanib and 96.2% with placebo. The proportions of patients with ≥1 dose reduction were 40.6% and 4.5%, and the proportions with ≥1 dose reduction and/or treatment interruption were 48.3% and 12.2%, in the nintedanib and placebo groups, respectively. Mean±SD durations of treatment interruption were 23.1±17.4 and 19.7±19.8 days with nintedanib and placebo, respectively. Diarrhoea was the reason for 59.2% of dose reductions and 41.2% of treatment interruptions in the nintedanib group, and for 30.8% and 19.4% of these dose adjustments in the placebo group, respectively. Treatment was permanently discontinued before week 52 due to AEs in 13.9% and 7.3% of patients in the nintedanib and placebo groups, respectively.

Conclusion: Over 52 weeks of treatment in the SENSCIS trial, most patients remained on therapy, suggesting that the dose adjustments used to manage AEs were effective at minimising treatment discontinuations.