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

Abstract

BackgroundIntravenous belimumab plus standard of care (SoC) is approved in the USA and Europe for treatment of active, autoantibody-positive systemic lupus erythematosus (SLE).MethodsThis 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.ResultsThe 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.ConclusionsIn patients with SLE from North East Asia, belimumab significantly improved disease activity, while reducing prednisone use, with no new safety issues.

New Drug Therapies for Systemic Lupus Erythematosus: A Systematic Review

“…The subcutaneous belimumab study [9] had the same primary endpoint as the BLISS-studies and also succeeded in meeting it. Comparable with the ILLUMINATE-trials [5,6], there was a significantly higher proportion of SRI-5 to 8 responders 3 in the belimumab group. Time to the first severe flare as measured with the modified SLE flare index was also significantly greater in the belimumab group.…”

“…In this context, 19 articles were shortlisted from the illustrated research, 7 of those [5][6][7][8][9][10][11][12] were chosen for analysis. The drugs whose effects were analysed in this review are tabalumab (6,7), belimumab [7][8][9], atacicept [10] and epratuzumab [11].…”

“…Tabalumab the ILLUMINATE studies: Tabalumab is a human IgG4 monoclonal antibody binding and neutralizing both soluble and membrane-bound BAFF [5]. The ILLUMINATE studies were published in 2015 (online publication in 2016) and tested the efficiency of subcutaneous tabalumab in a sample of about 1,100 patients each.…”

Pharmacokinetics, Pharmacodynamics and Safety of Belimumab in Chinese Patients with Systemic Lupus Erythematosus: A Phase I, Open-Label Study

“…The approval of belimumab for adults in Japan was based on the results of two pivotal phase 3 studies, including a study undertaken in Northeast Asia [6,8]. This phase 3, randomized, double-blind study (BEL113750; NCT01345253) was conducted in China, Japan, and South Korea to assess the efficacy and safety of belimumab 10 mg/kg IV every 4 weeks for 48 weeks, compared with placebo, both as add-on to standard of care in patients with SLE, 77% of whom were from China [8]. In this study, belimumab significantly reduced disease activity with a safety profile similar to that of placebo [8].…”

Acthar Gel (repository corticotropin injection) for persistently active SLE: study design and baseline characteristics from a multicentre, randomised, double-blind, placebo-controlled trial

“…18 19 Significant benefits of RCI compared with placebo were observed in secondary analyses of total hybrid SLE Disease Activity Index (hSLEDAI), total British Isles Lupus Assessment Group-2004(BILAG-2004 and Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) scores at week 8; benefits were also significant in post hoc analyses of the SLE Responder Index-4 (SRI-4) at week 8. 18 The hSLEDAI is identical to the Safety of Estrogens in Lupus National Assessment-SLEDAI used in clinical trials for belimumab [19][20][21][22] but uses the proteinuria definition from the SLE Disease Activity Index-2000 (SLEDAI-2K). In a separate post hoc analysis of these pilot study data, treatment with RCI demonstrated sustained improvements in disease activity over the 52-week study period.…”