medwireNews: More patients of Black African ancestry with systemic lupus erythematosus (SLE) respond to belimumab than placebo, but unlike in pivotal clinical trials, in which this group was underrepresented, the difference was not significant, say EMBRACE researchers.
The phase 4 trial found that 48.7% of 299 individuals randomly assigned to receive intravenous (IV) belimumab 10 mg/kg had an SRI response with modified proteinuria scoring adapted from the SLEDAI-2K (SRI-S2K) after 52 weeks.
This was numerically, but not significantly, higher than the response rate of 41.6% observed among the 149 participants randomly assigned to receive placebo, report Damon Bass (GlaxoSmithKline, Collegeville, Pennsylvania, USA) and co-authors in Arthritis & Rheumatology.
They say: “Although the magnitude of the treatment group difference in favor of belimumab is lower in this study […] when compared with those of the two pivotal Phase 3 studies of IV belimumab (BLISS-52: 58% belimumab, 44% placebo […] BLISS-76: 43% belimumab, 34% placebo […]), the efficacy results are directionally consistent.”
The investigators suggest that the differences in outcomes could be due to the fact that the EMBRACE population was “generally less immunologically active than the overall population in the pivotal Phase 3 studies” and that statistical power was reduced when fewer than planned participants were randomized.
Nonetheless, the data “support the post hoc analysis of [a] previous Phase 2 study, which showed an improved SELENA-SLEDAI (SS) response with belimumab versus placebo in patients of Black African ancestry,” the team remarks.
In addition, Bass et al found that significantly more patients in the belimumab group achieved a durable SRI-S2K response from week 44 to 52 than in the placebo group, at 42.3% versus 32.2%, while the mean duration of the longest response in people with one or more responses was greater with belimumab than placebo (172.9 vs 139.1 days).
Subgroup analyses showed that response rates were significantly higher with belimumab versus placebo for people with baseline SS-S2K scores of 10 or higher (52.5 vs 40.9%), positivity for anti-double-stranded (ds)DNA antibodies (46.4 vs 36.4%), low complement levels (47.2 vs 24.6%), and anti-dsDNA positivity plus low complement levels (45.1 vs 24.0%).
The researchers also report that “although this study was not powered to determine a treatment difference in renal endpoints, patients treated with belimumab had an improved SS-S2K renal domain score, decrease in proteinuria, and a downward shift in proteinuria for patients with high proteinuria at baseline.”
The authors say that belimumab “was generally well-tolerated” and “no new safety signals were observed.” Adverse events (AEs) of any grade were reported in 83.7% of people who received belimumab and 87.3% of those who received placebo, with serious AEs occurring in a respective 10.9% and 18.8%. Discontinuations due to AEs occurred in 6.6% and 7.3%, respectively.
Bass and colleagues conclude that their study “provides clinically meaningful evidence to inform clinicians regarding the management of their patients of Black African ancestry, especially those with [high disease activity], an SLE patient population with high unmet needs.”
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