The results of a randomised controlled trial, published in Annals of Internal Medicine, found that a new drug treatment regimen, using belimumab soon after rituximab, reduced a disease-related autoantibody and severe disease flares in lupus patients.
Systemic lupus erythematosus (SLE or lupus) is a long-term autoimmune condition, causing a variety of problems including joint pain, skin rashes, kidney disease and tiredness. While there is no known cure for this debilitating disease, the BEAT-Lupus clinical trial found that the combination of belimumab and rituximab shows promising results; reducing severe lupus flares by 3-fold for patients who had persistent, severe lupus disease requiring rituximab therapy at the beginning of the study.
Senior author Professor Caroline Gordon, Emeritus Professor of Rheumatology and member of the Institute of Inflammation and Ageing’s Rheumatology Research Group, together with colleagues from University College London conducted a phase 2 randomised trial involving 52 patients with SLE that was refractory to conventional treatment and whose physicians had recommended rituximab therapy. Patients were treated with rituximab and then randomly assigned four to eight weeks later to receive intravenous belimumab or placebo for 52 weeks.
The researchers found that IgG anti-dsDNA antibody levels were lower in belimumab-treated patients at 52 weeks compared with placebo-treated patients (geometric mean, 47 versus 103 IU/mL; 70 percent greater reduction from baseline). The risk for severe flare was reduced significantly with belimumab versus placebo (hazard ratio, 0.27), with three and 10 severe flares in the belimumab and placebo groups, respectively. There was no increase seen in the incidence of serious adverse events in the belimumab group.
Professor Michael Ehrenstein, Chief Investigator of the BEAT-Lupus trial, said: “Thanks to the dedication of the lupus teams at participating hospitals we are delighted to not only have completed recruitment, but also to provide preliminary evidence for a clinical benefit of the combination of rituximab and belimumab, compared to patients treated with rituximab alone.”
"These findings support further exploration of belimumab after rituximab as the first combination biologic therapy for patients with SLE, at least in those whose disease is refractory to conventional therapy and/or requires high corticosteroid dosages," the authors write.
Professor Gordon previously pioneered the methodology for assessing lupus disease activity and flares using the BILAG-2004 index. The main secondary clinical outcome of reduction of severe lupus flare in the BEAT-Lupus trial was based on this work, and flare was defined using this index.
She explained: “We were delighted to find that this treatment regimen not only reduced disease causing autoantibodies but also reduced severe flares which cause very distressing symptoms and disruption to patients’ lives. This study offers the hope that this combination of drugs will be useful in the future if the results are confirmed in a larger trial.”
The study was funded primarily by Versus Arthritis; GlaxoSmithKline provided belimumab free of charge, as well as some additional funding.