Background/Purpose: Black patients have more severe SLE and more frequent lupus nephritis vs other racial groups. Efficacy and safety of intravenous (IV) belimumab was demonstrated in three Phase 3 SLE studies; few black patients were included, limiting subgroup analyses. The EMBRACE study assessed efficacy and safety of IV belimumab plus standard of care (SoC) in black patients with SLE. Primary and key secondary endpoints have been presented;¹ here we focus on efficacy in patients with high disease activity (HDA) and renal manifestations.

Methods: EMBRACE (NCT01632241; GSK study 115471) is a multicenter, double-blind, placebo-controlled trial in patients of self‑identified black race, ≥18 years, with active SLE by ACR criteria at screening. Patients were randomized (2:1) to receive monthly belimumab 10 mg/kg IV or placebo, plus SoC. The primary endpoint was the difference in modified SLE Responder Index (SRI-S2K) response rates between belimumab and placebo. SRI-S2K incorporates the SLEDAI-2K (S2K) proteinuria definition ( >0.5 mg/24 h) rather than the SELENA-SLEDAI (SS) version ( >0.5 mg/24-h increase). A response is defined as ≥4‑point reduction in S2K, no worsening [increase < 0.3] in Physician’s Global Assessment, and no new BILAG A/2 B domain scores. SRI response (SS proteinuria scoring) at Week 52 was a key secondary endpoint. Subgroup analyses of SRI-S2K and SRI in patients with HDA (anti-dsDNA antibody positive, hypocomplementemia, or high SS-S2K scores [SS with S2K proteinuria scoring]) at baseline were performed. Other endpoints included time to renal flare, change from baseline in SS-S2K renal domain, and in proteinuria, over 52 weeks.

Results: No significant differences were seen in the mITT population (N=448) for SRI-S2K (Table). Among patients meeting HDA definitions at baseline, greater proportions were SRI-S2K responders at Week 52 with belimumab vs placebo; in the high anti-dsDNA group, the difference numerically favored belimumab. Similar results were observed with the SRI.

Belimumab patients (mITT) had a 46% lower risk of a renal flare vs placebo (hazard ratio [95% CI]: 0.54 [0.21, 1.36]; p=0.1880). Among those with baseline renal involvement measured by SS-S2K, numerically more belimumab patients experienced improvements in this domain at Week 52 vs placebo (23/55 [41.8%] vs 7/34 [20.6%]). Among those without baseline renal involvement measured by SS-S2K, the percentage worsening at Week 52 was low for both groups (placebo: 9/115 [7.8%], belimumab: 15/244 [6.1%]). In patients with baseline proteinuria >0.5 g/24 h, median (interquartile range) percentage reduction at Week 52 was numerically greater with belimumab (-65.3% [-81.1, -38.8%], n=38) vs placebo (-32.9% [-76.6, 36.3%], n=23; p=0.0558); more of these patients experienced proteinuria normalization (values ≤0.5 g/24 h) with belimumab (16/38 [42.1%]) vs placebo (6/23 [26.1%]) at Week 52. No new safety concerns were identified.

Conclusion: Black patients with SLE and HDA demonstrate benefits with belimumab vs placebo, with reductions in disease activity and SLEDAI renal domain scores.

Reference: ¹D’Cruz D et al Lupus Sci Med 2019;6.

Study funding: GSK. Medical writing support: Louisa McKay, PhD, Fishawack Indicia Ltd, UK (funded by GSK).

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/efficacy-of-belimumab-in-patients-of-black-race-with-systemic-lupus-erythematosus-and-high-disease-activity-or-renal-manifestations/