Background/Purpose: To assess the efficacy and safety of belimumab (BEL) administered subcutaneously plus standard SLE care (SoC) in patients with active SLE.

Methods:

BLISS-SC (BEL112341; NCT01484496) is a randomized, double-blind, placebo-controlled trial.

Patients with SLE with SELENA-SLEDAI (SS) score ≥8, receiving stable SLE therapy for ≥30 days were randomized (2:1) to receive weekly BEL 200 mg or placebo (PBO), administered subcutaneously (using a prefilled syringe), plus SoC. The primary endpoint was SLE Responder Index 4 (SRI4; ≥4 point reduction in SS, increase of <0.3 in Physician’s Global Assessment and no new BILAG A organ domain score or 2 new BILAG B organ domain scores, all compared with baseline) response rate at week 52. Secondary endpoints included time to severe flare and reduction in corticosteroid dose. Safety was assessed using adverse events (AEs).

Results:

839 adults enrolled; 3 patients were randomized but did not receive study drug and were removed from the intent-to-treat population. Baseline disease characteristics were similar between groups: mean (standard deviation [SD]) age was PBO 39.6 (12.61), BEL 38.1 (12.10) years; median (range) SLE disease duration was PBO 4.6 (0–38), BEL 4.3 (0–35) years; mean (SD) SS was PBO 10.3 (3.0), BEL 10.5 (3.2). SRI4 response at week 52 was: PBO 48.7% vs BEL 61.4%, odds ratio 1.65, p=0.0009 (95% CI 1.23, 2.22), with each individual component achieving statistical significance (all p≤0.0247). SRI4 response was significantly greater with BEL compared with PBO as early as week 16 and was sustained for 52 weeks. SRI5 response was significantly greater with BEL compared with PBO from week 12 and SRI6, 7 and 8 responses were significantly greater from week 8; all were sustained for 52 weeks (p≤0.0002, week 52). The BEL group was 50% less likely to experience a severe flare (hazard ratio = 0.50, p=0.0003) relative to the PBO group; time to severe flare for subjects experiencing a flare was PBO 116.5 vs BEL 170.0 days. More BEL patients were able to reduce steroid dose by ≥25% to ≤7.5 mg/day during weeks 40–52, but this did not achieve statistical significance: PBO 11.9% vs BEL 18.2%, odds ratio 1.65, p=0.0732 (95% CI 0.95, 2.84). Treatment compliance with the subcutaneous injections according to patient diaries was ≥96% in both groups.

Overall study withdrawals (PBO 23.6%, BEL 16.7%) included: AEs PBO 8.9%, BEL 7.2%; subject request PBO 5.4%, BEL 2.2%; lack of efficacy PBO 3.6%, 2.7% BEL. Serious AEs (PBO 15.7%, BEL 10.8%) included: infections/infestations PBO 5.4%, BEL 4.1%; renal/urinary PBO 2.5%, BEL 1.4%; nervous system PBO 2.1%, BEL 1.4%. The incidence of depression/suicide/self-injury was PBO 3.6%, BEL 3.1%. Five deaths occurred: PBO 0.7% (one each of hematologic and vascular), BEL 0.5% (three infections).

Conclusion:

BEL 200 mg administered weekly via subcutaneous injection plus SoC significantly improved SRI response and decreased time to severe flare compared with PBO plus SoC, and safety with BEL plus SoC was similar to that with PBO plus SoC.

Disclosures: GlaxoSmithKline (GSK) and Human Genome Sciences (HGS) sponsored and conducted this clinical trial. Katie White, PhD, Fishawack Indicia Ltd, UK, provided editorial support, funded by GSK.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/a-randomized-double-blind-placebo-controlled-52-week-study-of-the-efficacy-and-safety-of-belimumab-administered-subcutaneously-plus-standard-care-to-patients-with-systemic-lupus-erythematosus-sle/