BEAT LUPUS
Research type
Research Study
Full title
Safety and efficacy of Belimumab After B cell depletion therapy in systemic LUPUS erythematosus
IRAS ID
195085
Contact name
Michael Ehrenstein
Contact email
Sponsor organisation
University College London
Eudract number
2015-005543-14
Duration of Study in the UK
3 years, 6 months, 1 days
Research summary
Summary of Research
This study aims to find out whether a drug called Belimumab when used after B cell depletion therapy is safe and effective in reducing systemic lupus erythematosus (lupus) disease activity. Many patients respond well to B cell depletion therapy. However, for a group of these patients their lupus returns quickly. Evidence suggests that patients whose B cell numbers rapidly increase (B cell repopulation) after rituximab are prone to flare more quickly than those patients whose B cells repopulate more slowly. Previous research studies at UCL have shown that a chemical called BAFF increases after rituximab. BAFF helps B cells to survive and when BAFF levels increase the production of the harmful autoantibodies also increase.Belimumab is a drug which blocks the actions of BAFF and has been shown to have some beneficial effects in lupus. It is hoped that blocking BAFF soon after rituximab will both delay the reappearance of the B cells that cause disease and prevent the surge in BAFF levels which can stimulate the production of autoantibodies such as anti-DNA antibodies.The research team is based University College London Hospital and the coordinating team at UCL, the trial is funded by Arthritis UK. The study will recruit 50 patients with lupus from specialist lupus treatment centres across the country.Eligible patients who take part in the study will be randomised to either receive belimumab or placebo (normal saline), half the patients receive belimumab and half receive placebo. The decision as to which treatment is given will be made by a computer.Study participants will attend their hospital for an infusion of the study medication which will last an hour usually every four weeks. Patients taking part in the study will need to attend their hospital 21 times over a period of 15 months.
Summary of Results
The BEAT-LUPUS clinical trial has shown that the combination of belimumab and rituximab is safe for patients with systemic lupus erythematosus, and provides preliminary evidence for its effectiveness. BEAT-LUPUS not only met its primary endpoint, a reduction in the pivotal biomarker for Systemic Lupus Erythematosus (SLE), serum IgG anti-dsDNA antibody levels at 52 weeks, but also a key clinical secondary endpoint demonstrating a reduction in severe flares in patients with lupus treated with belimumab, compared to placebo, after rituximab therapy. The threefold reduction in the risk of severe flares by belimumab after rituximab over the 12 months of the trial suggests a marked effect of this combination which was not anticipated in a relatively small phase II trial. In comparison, more than 800 patients were recruited to the phase III trial of belimumab alone several years ago. We also showed that belimumab after B cell depletion with rituximab is not associated with more adverse effects than rituximab alone. Belimumab significantly suppressed B cell repopulation compared to placebo at 52 weeks. These results will have an impact on progressing this therapeutic strategy for SLE and the potential to improve the outcome of the many lupus patients refractory to conventional therapy treated with rituximab. A larger (phase III) trial is needed to confirm these results.
REC name
London - Hampstead Research Ethics Committee
REC reference
16/LO/1024
Date of REC Opinion
6 Jul 2016
REC opinion
Further Information Favourable Opinion