A pivotal phase III, randomised, placebo-controlled study of belimumab in patients with systemic lupus erythematosus located in China, Japan and South Korea

Abstract

Background: Intravenous belimumab plus standard of care (SoC) is approved in the USA and Europe for treatment of active, autoantibody-positive systemic lupus erythematosus (SLE).

Methods: This phase III, multicentre, randomised, double-blind, placebo-controlled study (BEL113750; NCT01345253) was conducted in 49 centres across China, Japan and South Korea (May 2011-September 2015). Patients with SLE were randomised 2:1 to intravenous belimumab 10 mg/kg or placebo, plus SoC, every 4 weeks until Week 48. The primary endpoint was the SLE Responder Index (SRI) 4 response rate at Week 52. Secondary endpoints were the percentage of patients with ≥4 point reduction in Safety of Oestrogens in Lupus Erythematosus National Assessment-SLE Disease Activity Index (SELENA-SLEDAI), SRI7, time to first severe flare and number of days prednisone (or equivalent) dose ≤7.5 mg/day and/or reduced by 50% from baseline. Safety was assessed.

Results: The modified intent-to-treat population included 677 patients (belimumab n=451, placebo n=226). At Week 52, the SRI4 response rate was higher with belimumab versus placebo (53.8% vs 40.1%; OR: 1.99 (95% CI: 1.40, 2.82; P=0.0001)). The percentages of patients with a ≥4 point reduction in SELENA-SLEDAI and an SRI7 response were significantly greater for belimumab versus placebo. Patients in the belimumab group had a 50% lower risk of experiencing a severe flare than those receiving placebo (P=0.0004). In patients with baseline prednisone dose >7.5 mg/day, there was a significant reduction in steroid use favouring belimumab (P=0.0228). The incidence of adverse events was similar between groups.

Conclusions: In patients with SLE from North East Asia, belimumab significantly improved disease activity, while reducing prednisone use, with no new safety issues.

Keywords: Disease Activity; Systemic Lupus Erythematosus; Treatment.

Figure 1

(A) Study design; (B) Consolidated Standards of Reporting Trials (CONSORT) flow diagram. ^aFollow-up period for those not entering the open-label period; ^blast dose for those not entering the open-label period.

Figure 2

Efficacy endpoints, by visit (modified intent-to-treat population). (A) SRI4 response; (B) SELENA-SLEDAI ≥4 point reduction; (C) SRI7 response and (D) time to first severe flare. *P<0.05 (logistic regression model for belimumab vs placebo with independent variables treatment group, country, baseline SELENA-SLEDAI score (≤9 vs ≥10) and baseline complement levels (low C3 and/or C4 vs no low C3 or C4)). C3/C4, complement 3/complement 4; SELENA-SLEDAI, Safety of Oestrogen in Lupus Erythematosus National Assessment-SLE Disease Activity Index; SFI, SLE Flare Index; SRI, SLE Responder Index.

Figure 3

Histogram showing the number of days of daily prednisone dose ≤7.5 mg/day (or equivalent) and/or reduced by 50% from baseline among patients with baseline daily prednisone dose >7.5 mg/day (mITT population).^aHistogram produced post hoc; the number of days indicates the midpoint of the category, that is, Day 30 represents Days 15–45. mITT, modified intent-to-treat.