Safety and efficacy of rituximab in systemic sclerosis (DESIRES): open-label extension of a double-blind, investigators-initiated, randomised, placebo-controlled trial

Abstract

Background: Results from the double-blind phase 2 DESIRES trial showed that rituximab improves skin thickening in systemic sclerosis. Here, we present the findings of a subsequent 24-week open-label extension phase.

Methods: Patients with systemic sclerosis aged 20-79 years, who fulfilled the 2013 American College of Rheumatology and European League Against Rheumatism classification criteria, with a baseline modified Rodnan Skin Score (mRSS) of 10 or greater were enrolled into the DESIRES trial, which was an investigator-initiated, phase 2, double-blind, randomised controlled trial of rituximab versus placebo conducted at four sites in Japan. After completion of 24 weeks of treatment with either rituximab or placebo, patients in both groups received a further 24 weeks of rituximab (375 mg/m² intravenously, once per week for 4 consecutive weeks) in an open-label extension. The primary endpoint of the double-blind trial was mRSS at week 24, which was reassessed at week 48 in the open-label extension. All endpoints were exploratory. Safety analyses included all participants who received at least one dose of study drug; efficacy analyses included those who had received at least one dose and undergone efficacy assessment at 24 weeks in the double-blind phase and at 48 weeks in the extension phase. The DESIRES study is registered with ClinicalTrials.gov, NCT04274257, and UMIN-CTR, UMIN000030139.

Findings: Between Nov 28, 2017, and Nov 6, 2018, 56 patients were randomly assigned to either rituximab (n=28) or placebo (n=28) in a double-blind study. 26 patients initially assigned to rituximab and 20 assigned to placebo transitioned to the open-label extension and all received at least one dose of rituximab; 24 participants in the rituximab-rituximab group and 19 in the placebo-rituximab group completed the extension phase. In the rituximab-rituximab group, there was an improvement in mRSS from baseline at week 24 (-5·81 [SD 3·16]), with further improvement at week 48 (-8·88 [3·10]). In the placebo-rituximab group, mRSS worsened at week 24 (2·14 [SD 5·51]) but improved at the week 48 assessment (-6·05 [4·43]). One patient each in the rituximab-rituximab and placebo-rituximab groups experienced one serious adverse event during the open-label phase (cholangitis and pneumococcal pneumonia, respectively). There were no deaths during follow-up.

Interpretation: Two courses of rituximab is a safe treatment that can provide sustained improvement in systemic sclerosis for at least 48 weeks.

Funding: Japan Agency for Medical Research and Development.

Translation: For the Japanese translation of the abstract see Supplementary Materials section.