Belimumab after rituximab reduces risk for severe flare in SLE

Treatment with belimumab following rituximab significantly lowers serum IgG anti-dsDNA antibody levels and the risk for severe flare in patients with systemic lupus erythematosus (SLE) that is refractory to conventional therapy, reveals a study.

A team of investigators conducted a phase II, randomized, double-blind, placebo-controlled, parallel-group, superiority trial in England and, between 2 February 2017 and 28 March 2019, recruited 52 patients who had SLE refractory to conventional therapy and whose physicians had recommended rituximab. Participants were treated with rituximab and 4–8 weeks later randomized to receive intravenous belimumab or placebo for 52 weeks.

IgG anti-dsDNA antibody levels at 52 weeks were lower in the belimumab group compared with the placebo group (geometric mean, 47 IU/mL, 95 percent confidence interval [CI], 25–88 vs 103 IU/mL, 95 percent CI, 49–213; 70-percent greater reduction from baseline, 95 percent CI, 46–84; p<0.001).

Belimumab also reduced the risk for severe flare (BILAG-2004 grade A) relative to placebo (hazard ratio, 0.27, 95 percent CI, 0.07–0.98; log-rank p=0.033), with 10 severe flares in the latter and only three in the intervention arm. The incidence of serious adverse events did not increase with belimumab.

In a subset of patients (n=25) with available data, belimumab significantly suppressed B-cell repopulation compared with placebo (geometric mean, 0.012 × 10⁹/L, 95 percent CI, 0.006–0.014 vs 0.037 × 10⁹/L, 95 percent CI, 0.021–0.081) at 52 weeks.

“The results suggest that this combination could be developed as a therapeutic strategy,” the investigators said, noting that the study was limited by its small sample size and biomarker endpoint.