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Objectives: To assess the effects of belimumab on disease activity across multiple organ domains in Japanese patients from the Phase 3 randomized, double-blind, North-East Asia study, BEL113750 (NCT01345253). Methods: Patients, aged ≥18 years, with American College of Rheumatology-defined systemic lupus erythematosus (SLE) and a Safety of Estrogen in Lupus Erythematosus National Assessment-SLE Disease Activity Index (SELENA-SLEDAI) score ≥8 at screening, on stable SLE treatment, were randomized 2:1 to receive intravenous belimumab 10mg/kg or placebo, plus standard of care, on Days 0, 14, and 28, then 4-weekly until Week 48. Patients were assessed for SELENA-SLEDAI and British Isles Lupus Assessment Group (BILAG) organ system improvement/worsening between baseline and Week 52. Results: Sixty patients (belimumab, n = 39; placebo, n = 21) were enrolled in Japan. Improvement was seen in a greater proportion of belimumab patients, compared with placebo, in most SELENA-SLEDAI and BILAG domains (significant for the mucocutaneous domain). Worsening occurred in SELENA-SLEDAI hematologic and renal systems (<7% both treatments) and in a number of BILAG systems: <11% (placebo) and <8% (belimumab), although the small sample size should be noted. Conclusion: Organ system improvements were seen in more Japanese belimumab-treated than placebo-treated patients, providing further evidence supporting belimumab use in Japanese patients with SLE. [ABSTRACT FROM AUTHOR]

Objectives: To assess the efficacy and safety of intravenous (IV) belimumab plus standard systemic lupus erythematosus (SLE) therapy standard of care (SoC) in Japanese patients with SLE. Methods: A Phase 3, multicenter, double-blind, placebo-controlled, 52-week study (BEL 113750; NCT01345253) in patients with SLE, randomized 2:1 to belimumab 10mg/kg plus SoC or placebo plus SoC to Week 48. Results: Sixty of 707 randomized patients were enrolled from study centers in Japan (belimumab, n¼39; placebo, n¼21). In this cohort, more patients achieved SLE Responder Index 4 response at Week 52 in the belimumab group compared with placebo (46.2% [18/39] vs. 25.0% [5/20]; odds ratio, 2.57 [95% confidence interval: 0.78, 8.47]; p¼.1204). Fewer patients receiving belimumab experienced a severe flare through Week 52, with longer median time to flare compared with placebo. More patients with baseline prednisone dose >7.5mg/d receiving belimumab had a dose reduction of -25% from baseline to -7.5 mg/d during Weeks 40-52, compared with placebo. No new safety issues were identified within the Japanese cohort. Conclusion: In Japanese patients with SLE, belimumab improved disease activity, with efficacy and safety results similar and consistent to the pivotal Phase 3 trials, suggesting that belimumab is a potential treatment option in this population. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the long-term safety and efficacy of belimumab in patients with systemic lupus erythematosus (SLE) from Japan and South Korea., Methods: In this phase III, open-label continuation study (BEL114333; NCT01597622), eligible completers of BEL113750 (NCT01345253) or BEL112341 (NCT01484496) received intravenous belimumab 10 mg/kg every 28 days for ≤7 years. Primary endpoint was safety. Secondary endpoints: SLE Responder Index (SRI)4 response rate, proportion of patients meeting individual SRI4 criteria, SLE flares and prednisone use. Analyses were based on observed data from the first belimumab exposure (either in parent or current study) through to study end., Results: Of 142 enrolled patients who received belimumab, 73.2% completed the study. The study population comprised patients with moderate SLE, mean (SD) Safety of Estrogens in Lupus Erythematosus National Assessment-SLE Disease Activity Index (SELENA-SLEDAI) baseline score of 9.3 (3.9) and 98.6% receiving corticosteroids. Most patients (97.9%) experienced adverse events (AEs); 33.8% experienced serious AEs. Increase in SRI4 (Year 1, Week 24: 47.8%; Year 6, Week 48: 68.2%) and SELENA-SLEDAI responders suggested reductions in disease activity. Proportions of patients with no worsening in Physician Global Assessment/no new organ damage remained stable throughout. Severe SLE flares occurred in 14.8% of patients. Among patients with baseline prednisone-equivalent dose >7.5 mg/day (n=81), the median (min, max) number of days anytime post-baseline that the daily dose was ≤7.5 mg/day or had been reduced by 50% from baseline was 584 (0, 2267)., Conclusions: Favourable safety profile and treatment responses were maintained for ≤7 years in patients with SLE from Japan and South Korea., Competing Interests: Competing interests: YT received research grants from Mitsubishi-Tanabe, Chugai, AbbVie, Takeda, UCB, Daiichi-Sankyo and Eisai and speaking fees and/or honoraria from Daiichi-Sankyo, Eli Lilly, Novartis, YL Biologics, Bristol-Myers, Eisai, Chugai, AbbVie, Astellas, Pfizer, Sanofi, Asahi-Kasei, GlaxoSmithKline, Mitsubishi-Tanabe, Gilead and Janssen. S-CB has no conflicts of interest to declare. DB, PC, MC, KD, BJ, RK, JL, PM and DAR are employees of GlaxoSmithKline and hold stocks and shares in the company., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

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., Competing Interests: Competing interests: DB, MC, SE, DG and DAR are employees of GSK and hold shares in the company. YT receives consulting fees, speaking fees and/or honoraria from AbbVie, Chugai, Daiichi-Sankyo, Bristol-Myers Squibb, Mitsubishi-Tanabe, Astellas, Takeda, Pfizer, Asahi-Kasei, YL Biologics, Sanofi, Janssen, Eli Lilly and GSK and has received research grants from Mitsubishi-Tanabe, Takeda, Daiichi-Sankyo, Chugai, Bristol-Myers Squibb, MSD, Astellas, AbbVie and Eisai., (© 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.)