Efficacy of belimumab combined with rituximab in severe systemic lupus erythematosus: study protocol for the phase 3, multicenter, randomized, open-label Synbiose 2 trial

Mieke van Schaik, Eline J Arends, Darius Soonawala, Ellen van Ommen, Karina de Leeuw, Maarten Limper, Pieter van Paassen, Tom W J Huizinga, René E M Toes, Cees van Kooten, Joris I Rotmans, Ton J Rabelink, Y K Onno Teng*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

BACKGROUND: Belimumab, an anti-B-cell activating factor antibody, is approved for the treatment of auto-antibody positive systemic lupus erythematosus with a high degree of disease activity. Anti-CD20 B cell depletion with rituximab is used in refractory SLE as well, although with variable responses. We hypothesized that incomplete B cell depletion, related to a surge in BAFF levels following rituximab treatment, can cause ongoing disease activity and flares. The Synbiose 1 study primarily focused on immunological effects and shows the preliminary clinical benefit of combined rituximab and belimumab in SLE. The Synbiose 2 study will evaluate the clinical efficacy of combining belimumab with rituximab in patients with severe SLE, allowing the tapering of prednisolone and mycophenolate.

METHODS: Synbiose 2 is a phase 3, multicenter, randomized, controlled, open-label 2-year clinical trial. Seventy adults with severe SLE including lupus nephritis will be randomized 1:1 to receive either standard of care consisting of prednisolone and mycophenolate as induction and maintenance treatment, or belimumab and rituximab combined with standard of care as induction treatment, followed by prednisolone and belimumab as maintenance treatment. The primary objective is to assess whether combined B cell therapy will lead to a reduction of treatment failure. Secondary endpoints are complete and partial clinical and renal response and the improvement of SLE-specific autoimmune phenomena. Safety endpoints include the incidence of adverse events, with a special interest in infections.

DISCUSSION: The Synbiose 2 trial is the first multicenter phase 3 clinical trial investigating combined B cell targeted therapy in SLE, including lupus nephritis. The outcome of this study will provide further evidence for the clinical efficacy of this new treatment strategy in severe SLE.

TRIAL REGISTRATION: ClinicalTrials.gov NCT03747159 . Registered on 20 November 2018.

Original languageEnglish
Article number939
Number of pages10
JournalTrials
Volume23
Issue number1
DOIs
Publication statusPublished - 12 Nov 2022

Keywords

  • Adult
  • Humans
  • Rituximab/adverse effects
  • Lupus Nephritis/chemically induced
  • Lupus Erythematosus, Systemic/diagnosis
  • Immunosuppressive Agents/adverse effects
  • Treatment Outcome
  • Prednisolone/adverse effects
  • Randomized Controlled Trials as Topic
  • Multicenter Studies as Topic
  • Clinical Trials, Phase III as Topic

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