Adding belimumab after rituximab significantly reduced systemic lupus erythematosus activity and symptoms without increased risk for infections or other adverse effects, a study found.
Researchers recruited 52 patients who were prescribed rituximab for refractory lupus at 16 centers in England. After four to eight weeks on the rituximab regimen, patients were randomly assigned to also receive intravenous belimumab or placebo for 52 weeks. GlaxoSmithKline provided belimumab for the trial free of charge, along with additional funding. Results were published Oct. 26 by Annals of Internal Medicine.
At 52 weeks, IgG anti-double-stranded DNA (anti-dsDNA antibody) levels were lower in patients treated with belimumab (geometric mean, 47 IU/mL; 95% CI, 25 to 88 IU/mL) compared with placebo (103 IU/mL; 95% CI, 49 to 213 IU/mL), and belimumab led to a 70% (95% CI, 46% to 84%) greater reduction from baseline P<0.001). A greater reduction in IgG anti-dsDNA antibody levels was also seen in the belimumab group at 24 weeks (P<0.001).
Compared with placebo, belimumab also reduced risk for a severe flare over 52 weeks by 73% (hazard ratio [HR], 0.27 [95% CI, 0.07 to 0.98]; unadjusted log-rank P=0.033). There were 10 severe flares in the placebo group and three in the belimumab group. However, differences in the combined outcome of moderate and severe flares did not achieve statistical significance (HR, 0.50 [95% CI, 0.21 to 1.20]; unadjusted log-rank P=0.124). For a subset of patients who provided samples for analysis, peripheral blood B-cell numbers were similar between groups up to 24 weeks but were higher in the placebo group at 52 weeks (P=0.031).
“These findings support further exploration of belimumab after rituximab as the first combination biologic therapy for patients with SLE [systemic lupus erythematosus], at least in those whose disease is refractory to conventional therapy and/or requires high corticosteroid dosages,” the study authors said. They noted that the results were consistent with the hypothesis that a surge in B-cell activating factor levels after rituximab treatment can trigger lupus exacerbations.
An accompanying editorial said, “B-cell depleting therapy may not benefit all SLE patients” but noted that for a subset, this combination may be highly effective with a reasonable safety profile. “Future studies are needed to determine the optimal sequence of treatments, clinical responses, characterization of patients likely to respond, and adverse event profiles in larger populations to help us better care for our patients with SLE,” the editorial said.