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.

• Authors: Fengchun Zhang, Sang-Cheol Bae, Damon Bass, Myron Chu, Sally Egginton, David Gordon, David A Roth, Jie Zheng, Yoshiya Tanaka
• Journal: Annals of the rheumatic diseases (Ann Rheum Dis) Vol. 77 Issue 3 Pg. 355-363 (03 2018) ISSN: 1468-2060 [Electronic] England
• PMID: 29295825 (Publication Type: Clinical Trial, Phase III, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Chemical References

• Antibodies, Monoclonal, Humanized
• Immunosuppressive Agents
• belimumab
• Prednisone

Topics

• Administration, Intravenous
• Adult
• Antibodies, Monoclonal, Humanized (adverse effects, therapeutic use)
• China
• Double-Blind Method
• Female
• Humans
• Immunosuppressive Agents (adverse effects, therapeutic use)
• Japan
• Lupus Erythematosus, Systemic (drug therapy)
• Male
• Middle Aged
• Prednisone (administration & dosage)
• Republic of Korea
• Severity of Illness Index
• Standard of Care
• Treatment Outcome