Abstract
Background Black patients have an increased prevalence and severity of systemic lupus erythematosus (SLE), alongside higher mortality rates. The efficacy and safety of intravenous (IV) belimumab has been demonstrated in several Phase 2/3 studies; however, the small number of black patients within these trials, and the conflicting results, have limited conclusions regarding efficacy in this population. The objective of this study was to specifically assess the efficacy and safety of IV belimumab plus standard of care (SoC) in black patients with active, auto antibody-positive SLE.
Methods EMBRACE (NCT01632241) is a randomized, multicenter, double-blind, placebo-controlled trial in patients of self identified black race, aged 18 years, with active SLE at screening. Patients were randomized (2:1) to monthly belimumab 10 mg/kg IV or placebo, plus SoC. The primary endpoint was the SLE Responder Index (SRI) response rate with modified SLEDAI-2K (S2K) scoring for proteinuria at Week 52 (SRI-S2K response required a 4 point reduction in the SELENA-SLEDAI (SS)-S2K, no worsening [increase of <0.3] in Physician’s Global Assessment (PGA), and no new BILAG A or 2 new B organ domain scores). Key secondary endpoints included SRI response rate with SS scoring of proteinuria at Week 52, time to first severe SFI flare, and reductions in prednisone dose by 25% to 7.5 mg/day during Weeks 4052. Subgroup analyses of the primary endpoint were also conducted. Step-down sequential testing was utilized to control the overall type 1 error rate (2-sided, alpha=0.05). Safety was assessed by monitoring adverse events (AEs).
Results The mITT population comprised 448 patients; 96.9% were female and mean (SD) age was 38.8 (11.42) years. Although the study did not achieve the primary endpoint, numerical trends were observed in favor of belimumab, and significant improvements were observed in subgroups with characteristics of high disease activity (HDA; table). Study withdrawals were similar between groups (belimumab 22.4%; placebo 24.2%) and AEs were the primary reason for withdrawals (belimumab 5.4%; placebo 6.7%). The percentage of patients who experienced an AE (belimumab 83.7%; placebo 87.3%) or serious AE (belimumab 10.9%; placebo 18.8%) was similar between groups. Two deaths occurred within the belimumab group (0.6%; pneumonia and meningitis); neither were established as directly related to belimumab.
Conclusions Whilst the primary endpoint of this study in black patients with SLE was not achieved, improvements in favor of belimumab were observed, with significant benefits in patients with HDA. The safety profile was acceptable and consistent with previous studies.
Funding Source(s): Study (BEL115471) funded by GSK.
