Long-term safety and efficacy of belimumab in Japanese patients with SLE: A 7-year open-label continuation study.

OBJECTIVES: Evaluate long-term safety, tolerability, and efficacy of belimumab in Japanese patients with systemic lupus erythematosus (SLE). METHODS: This was a subgroup analysis of Japanese patients who completed studies BEL113750 or BEL112341 and were enrolled in a Phase 3, open-label extension study (BEL114333; NCT01597622). Eligible patients received intravenous belimumab 10 mg/kg every 28 days for ≤7 years. Primary endpoint: safety and tolerability. Secondary endpoints included SLE Responder Index (SRI)-4 response rate, SRI-4 components, severe SLE flare, and use of corticosteroids/other SLE-related treatments. Analyses were based on observed data from first belimumab dose received in either parent or current study through to study end. RESULTS: Of 71 Japanese patients enrolled, 69.0% completed the study. Overall, 98.6% patients had adverse events (AEs); 32.4% had serious AEs. The proportion of SRI-4 responders increased progressively (Year 1, Week 24: 40.9% [27/66]; Year 7, Week 48: 84.6% [11/13]) as did the proportion of Safety of Estrogens in Lupus Erythematosus National Assessment-SLE Disease Activity Index responders. The proportion of patients with no worsening in PGA (91.2-100.0%) and no new organ damage (92.6-100.0%) remained stable over time. Severe SLE flare was experienced by 11.3% (8/71) of patients. Corticosteroid and immunosuppressant use decreased over time. CONCLUSIONS: Favourable safety profile and treatment responses with belimumab were maintained for ≤7 years in Japanese patients with SLE.

Efficacy of belimumab in patients with systemic lupus erythematosus from North East Asia: Results of exploratory subgroup analyses.

OBJECTIVES: To assess belimumab efficacy in patients from North East Asia (NEA) with systemic lupus erythematosus (SLE) in baseline demographic/disease characteristic subgroups. METHODS: This analysis of patient subgroups from BLISS-NEA (GSK Study 113750; NCT01345253) studied adults with SLE randomized to belimumab (10 mg/kg intravenous) or placebo. Primary endpoint, SLE Responder Index 4 (SRI-4) response rate at Week 52, was analysed in subgroups defined by gender, country, prednisone-equivalent dose, concomitant medications, Safety of Estrogens in Lupus National Assessment-SLE Disease Activity Index (SELENA-SLEDAI) score, complement (C) levels, anti-double-stranded deoxyribonucleic acid (dsDNA) positivity, Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index score. RESULTS: Patients (overall population: N = 677; belimumab: n = 451, placebo: n = 226) were from China (76.4%), Korea (14.8%), and Japan (8.9%). The mean age was 32.1 years; 92.9% were female. In the overall population, more belimumab (53.8%) than placebo (40.1%) patients were SRI-4 Week 52 responders (p = .0001). SRI-4 response rates by subgroups were generally consistent with the overall population. A greater response with belimumab was seen in patients with a baseline SELENA-SLEDAI score ≥10 versus ≤9 and patients with low C3/C4 levels and anti-dsDNA positive at baseline versus those 'NOT' (low C3 and/or C4 and anti-dsDNA positive). CONCLUSIONS: These findings continue to support the efficacy of belimumab in SLE.

Phase 3, long-term, open-label extension period of safety and efficacy of belimumab in patients with systemic lupus erythematosus in China, for up to 6 years.

OBJECTIVES: To evaluate the long-term safety and efficacy of belimumab in patients with systemic lupus erythematosus (SLE) in China. METHODS: In this phase 3, open-label extension period, eligible completers of study BEL113750 (NCT01345253) received intravenous belimumab 10 mg/kg monthly for ≤6 years. The primary endpoint was safety. Secondary endpoints included the SLE Responder Index (SRI)-4 response rate, severe SLE flares and changes in prednisone use. Analyses were based on observed data from the first dose of belimumab through to study end. RESULTS: Of the 424 patients who received belimumab, 215 (50.7%) completed the study, 208 (49.1%) withdrew and 1 patient died. Overall, 359/424 (84.7%) patients had adverse events (AEs), and 96/424 (22.6%) had serious AEs. 26/424 (6.1%) patients discontinued study treatment/withdrew from the study due to AEs. Postinfusion systemic reaction rate was 1.5 events/100 patient-years. Herpes zoster infection rate was 3.0 events/100 patient-years, of which 0.4 events/100 patient-years were serious events. One papillary thyroid cancer and one vaginal cancer were reported in year 0-1 and year 3-4, respectively. There were no completed suicides/suicide attempts and no reports of serious depression. The proportion of SRI-4 responders increased progressively (year 1, week 24: 190/346 (54.9%); year 5, week 48: 66/82 (80.5%)). Severe flares were experienced by 55/396 (13.9%) patients. For 335 patients with baseline prednisone-equivalent dose >7.5 mg/day, the number of patients with a dose reduction to ≤7.5 mg/day increased over time (year 1, week 24: 30/333 (9.0%); year 5, week 48: 36/67 (53.7%)). CONCLUSIONS: Favourable safety profile and disease control appeared to be maintained in patients with SLE in China for ≤6 years, consistent with previous belimumab studies.

Long-term open-label continuation study of the safety and efficacy of belimumab for up to 7 years in patients with systemic lupus erythematosus from Japan and South Korea.

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.