medwireNews: Following rituximab with the anti–B-cell activating factor (BAFF) monoclonal antibody belimumab may be a valid treatment option for patients with systemic lupus erythematosus (SLE) that is refractory to conventional therapy, phase 2 study data suggest.
Michael Ehrenstein (University College London, UK) and colleagues explain that although rituximab is often given to individuals with refractory SLE, the responses can be variable.
“One mechanism that may limit its effectiveness is the increase in BAFF levels after B-cell depletion,” which has been linked to increased disease flares, they say.
The researchers therefore investigated whether targeting BAFF could be associated with improved clinical outcomes and a lower frequency of flares after rituximab.
The BEAT-LUPUS trial included 52 patients with refractory SLE who were given rituximab 1 g (two doses 2 weeks apart) following a physician’s recommendation, and were then randomly assigned to receive intravenous belimumab 10 mg/kg at baseline, week 2, week 4, and every 4 weeks thereafter, or placebo for 52 weeks.
As reported in the Annals of Internal Medicine, serum immunoglobulin (Ig)G anti–double-stranded (ds)DNA antibody levels were significantly lower at 52 weeks in the belimumab versus the placebo group. Specifically, levels fell from a geometric mean of 162 IU/mL at baseline to 47 IU/mL at week 52 with belimumab and from 121 to 103 IU/mL with placebo, corresponding to a significant 70% greater reduction with belimumab.
The reduction in IgG anti-dsDNA antibody levels was also significantly greater with belimumab versus placebo week 24.
In addition, Ehrenstein and team found that the risk for severe flare (BILAG-2004 grade A) was a significant 73% lower among the people who received belimumab relative to those who received placebo, with three flares in the former group during treatment versus 10 in the latter.
In a subgroup of 25 participants who provided samples for analysis, the researchers observed that at 52 weeks peripheral blood B-cell numbers were significantly lower in the belimumab versus placebo groups (geometric mean, 0.012 vs 0.037 x 109/L) indicating that the monoclonal antibody “significantly suppressed B-cell repopulation compared with placebo.”
They conclude that these “data provide preliminary evidence of clinical benefit of belimumab after rituximab” and support further investigation of this regimen “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.”
In an accompanying commentary, Medha Barbhaiya (Hospital for Special Surgery, New York, USA) and Katherine Liao (Brigham and Women’s Hospital, Boston, Massachusetts, USA) caution that “the clinical significance of a reduced, but persistently positive, anti-dsDNA IgG level is not certain.”
They say: “While the investigators demonstrated reduction in flares in their secondary analysis, use of a primary clinical composite endpoint may provide better clinical interpretability and improve the ability to compare results with other SLE trials.”
Nonetheless, Barbhaiya and Liao acknowledge that studying SLE presents many challenges and conclude that the BEAT-LUPUS trial “sheds light on the potential synergy between [rituximab] and [belimumab] in this population of SLE patients.”
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Ann Intern Med 2021; doi:10.7326/M21-2078
Ann Intern Med 2021; doi:10.7326/M21-4124