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Objective: Enrollment of patients of Black African ancestry with systemic lupus erythematosus (SLE) in phase II and phase III of the belimumab trials was not reflective of the racial distribution observed in the lupus population. This study was undertaken to assess the efficacy and safety of intravenous (IV) belimumab plus standard therapy in patients of self‐identified Black race. Methods: EMBRACE (GSK Study BEL115471; ClinicalTrials.gov identifier: NCT01632241) was a 52‐week multicenter, double‐blind, placebo‐controlled trial in adults of self‐identified Black race with active SLE who received monthly belimumab 10 mg/kg IV, or placebo, plus standard therapy. The optional 26‐week open‐label extension phase included patients who completed the double‐blind phase. The primary end point of the study was SLE Responder Index (SRI) response rate at week 52 with modified proteinuria scoring adapted from the SLE Disease Activity Index 2000 (SLEDAI‐2K) (SRI–SLEDAI‐2K). Key secondary end points included SRI response rate at week 52, time to first severe SLE flare, and reductions in prednisone dose. Results: The modified intent‐to‐treat population comprised 448 patients, of whom 96.9% were women and the mean ± SD age was 38.8 ± 11.42 years. The primary end point (improvement in the SRI–SLEDAI‐2K response rate at week 52) was not achieved (belimumab 48.7%, placebo 41.6%; odds ratio 1.40 [95% confidence interval 0.93, 2.11], P = 0.1068); however, numerical improvements favoring belimumab were observed, in which the SRI–SLEDAI‐2K response rates were higher in those who received belimumab compared with those who received placebo, especially in patients with SLE who had high disease activity or renal manifestations at baseline. The safety profile of belimumab was generally consistent with that observed in previous SLE trials. Adverse events were the primary reasons for double‐blind phase withdrawals (belimumab 5.4%, placebo 6.7%). Conclusion: The primary end point of this study was not achieved, but improvement with belimumab versus placebo was observed, suggesting that belimumab remains a suitable treatment option for SLE management in patients of Black African ancestry. [ABSTRACT FROM AUTHOR]

The phase 2 placebo‐controlled, double‐blind PLUTO trial characterized the pharmacokinetics of belimumab plus standard systemic lupus erythematosus (SLE) therapy in patients with childhood‐onset SLE (cSLE) and demonstrated similar efficacy and safety to that in adult SLE. Patients with active cSLE aged 5‐17 years were randomized to intravenous belimumab 10 mg/kg every 4 weeks (n = 53). A linear 2‐compartment population pharmacokinetics (popPK) model with first‐order elimination was developed, and an exploratory exposure‐response analysis assessed the impact of between‐patient exposure variability on clinical response (SLE Responder Index 4 [SRI4]) in week 52, and occurrence of serious adverse events during the study. The popPK model estimated clearance of 158 mL/day, steady‐state volume of distribution of 3.5 L, terminal half‐life of 16.3 days, and distribution half‐life of 0.8 days in the overall population. Fat‐free mass (FFM) better characterized the pharmacokinetics than total body weight and was more consistent with allometric scaling theory; belimumab pharmacokinetics were largely determined by FFM. Age, sex, disease activity, and concomitant medication had no impact on pediatric belimumab exposure after accounting for body size. Individual and median steady‐state pediatric pharmacokinetic profiles were similar to known adult profiles and pediatric exposure estimates for belimumab 10 mg/kg intravenously were consistent with adult exposures. Exposures were similar between SRI4 responders and nonresponders, and patients who did or did not experience a serious adverse event. There was no clinically relevant correlation between exposure and efficacy or safety, confirming belimumab 10 mg/kg intravenous dose every 4 weeks as appropriate for pediatric patients with cSLE. [ABSTRACT FROM AUTHOR]

Objectives: This ongoing Phase-2, randomised, placebo-controlled, double-blind study evaluated the efficacy, safety and pharmacokinetics of intravenous belimumab in childhood-onset systemic lupus erythematosus (cSLE).Methods: Patients (5 to 17 years) were randomised to belimumab 10 mg/kg intravenous or placebo every 4 weeks, plus standard SLE therapy. Primary endpoint: SLE Responder Index (SRI4) response rate (Week 52). Key major secondary endpoints: proportion of patients achieving the Paediatric Rheumatology International Trials Organisation/American College of Rheumatology (PRINTO/ACR) response using 50 and '30 alternative' definitions (Week 52), and sustained response (Weeks 44 to 52) by SRI4 and Parent Global Assessment of well-being (Parent-global). Safety and pharmacokinetics were assessed. Study not powered for statistical testing.Results: Ninety-three patients were randomised (belimumab, n=53; placebo, n=40). At Week 52, there were numerically more SRI4 responders with belimumab versus placebo (52.8% vs 43.6%; OR 1.49 (95% CI 0.64 to 3.46)). PRINTO/ACR 30 alternative (52.8% vs 27.5%; OR 2.92 (95% CI 1.19 to 7.17)) and PRINTO/ACR 50 (60.4% vs 35.0%; OR 2.74 (95% CI 1.15 to 6.54)) responses were more frequent with belimumab than placebo, as were sustained responses for SRI4 (belimumab, 43.4%; placebo, 41.0%; OR 1.08 (95% CI 0.46 to 2.52)) and Parent-global (belimumab, 59.1%; placebo, 33.3%; OR 3.49 (95% CI 1.23 to 9.91)). Serious adverse events were reported in 17.0% of belimumab patients and 35.0% of placebo patients; one death occurred (placebo). Week-52, geometric mean (95% CI) belimumab trough concentration was 56.2 (45.2 to 69.8) µg/mL.Conclusion: The belimumab intravenous pharmacokinetics and benefit-risk profile in cSLE are consistent with adult belimumab studies and the 10 mg/kg every 4 weeks dose is appropriate.Trial Registration Number: NCT01649765. [ABSTRACT FROM AUTHOR]

Objective This extension study of the Phase III, randomized, placebo-controlled Belimumab International SLE Study (BLISS)-52 and BLISS-76 studies allowed non-US patients with SLE to continue belimumab treatment, in order to evaluate its long-term safety and tolerability including organ damage accrual. Methods In this multicentre, long-term extension study (GlaxoSmithKline Study BEL112234) patients received i.v. belimumab every 4 weeks plus standard therapy. Adverse events (AEs) were assessed monthly and safety-associated laboratory parameters were assessed at regular intervals. Organ damage (SLICC/ACR Damage Index) was assessed every 48 weeks. The study continued until belimumab was commercially available, with a subsequent 8-week follow-up period. Results A total of 738 patients entered the extension study and 735/738 (99.6%) received one or more doses of belimumab. Annual incidence of AEs, including serious and severe AEs, remained stable or declined over time. Sixty-nine (9.4%) patients experienced an AE resulting in discontinuation of belimumab or withdrawal from the study. Eleven deaths occurred (and two during post-treatment follow-up), including one (cardiogenic shock) considered possibly related to belimumab. Laboratory parameters generally remained stable. The mean (s. d.) SLICC/ACR Damage Index score was 0.6 (1.02) at baseline (prior to the first dose of belimumab) and remained stable. At study year 8, 57/65 (87.7%) patients had no change in SLICC/ACR Damage Index score from baseline, indicating low organ damage accrual. Conclusion Belimumab displayed a stable safety profile with no new safety signals. There was minimal organ damage progression over 8 years. Trial registration ClinicalTrials.gov, https://clinicaltrials.gov , NCT00424476 (BLISS-52), NCT00410384 (BLISS-76), NCT00732940 (BEL112232), NCT00712933 (BEL112234). [ABSTRACT FROM AUTHOR]

Objective: To investigate the long‐term safety and efficacy of intravenous (IV) belimumab plus standard of care (SOC) therapy for systemic lupus erythematosus (SLE) in patients with active, autoantibody‐positive SLE. Methods: The study was designed as a multicenter, open‐label, continuation study of IV belimumab given every 4 weeks in conjunction with SOC therapy in patients with SLE who completed a phase II, double‐blind study. Adverse events (AEs) and laboratory data were monitored from the first belimumab dose (in either study) until 24 weeks after the final dose. Efficacy assessments included SLE Responder Index (SRI) and flare index scores (each assessed at 16‐week intervals) and glucocorticoid use (assessed at 4‐week intervals). Results: Of the 476 patients in the parent study, 298 (62.6%) entered the continuation study, of whom 96 (32.2%) remained in the study. Patients received belimumab for up to 13 years (median duration of exposure 3,334.0 days [range 260–4,332 days], total belimumab exposure 2,294 patient‐years, median number of infusions 115.5 [range 7–155]). The percentage of patients with AEs each year remained stable or decreased. Normal serum IgG levels were maintained in the majority of patients over the study, and the rate of infections remained stable. The percentage of patients who achieved an SRI response increased from 32.8% (year 1) to 75.6% of those remaining on treatment at year 12. The glucocorticoid dose was decreased in patients who had been receiving >7.5 mg/day at baseline. Conclusion: This study is the longest to date to assess belimumab treatment in patients with SLE in clinical trials. Belimumab was well tolerated with no new safety concerns, and efficacy was maintained in patients who continued the study. For patients who initially exhibited a satisfactory response to belimumab, the treatment continues to be well tolerated and provides long‐term disease control. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the safety and efficacy of belimumab as adjunctive therapy to maintain remission in antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis (AAV). Methods: In this multicenter, double‐blind, placebo‐controlled study, patients with AAV (ages ≥18 years) were randomized 1:1 to receive azathioprine (2 mg/kg/day), low‐dose oral glucocorticoids (≤10 mg/day), and either intravenous belimumab (10 mg/kg) or placebo, following remission induction with rituximab or cyclophosphamide along with glucocorticoids. The primary end point was time to first protocol‐specified event (PSE), with first PSE defined as a Birmingham Vasculitis Activity Score (BVAS) of ≥6, presence of ≥1 major BVAS item, or receipt of prohibited medications for any reason, resulting in treatment failure (adjusted for ANCA type [proteinase 3 (PR3) or myeloperoxidase (MPO)], disease stage at induction, and induction regimen). Vasculitis relapse was defined as the PSE of either a BVAS activity score of ≥6 or receipt of prohibited medications for vasculitis. Changes in treatment practice led to truncation of the study population from ~300 patients to ~100 patients. Results: The intent‐to‐treat population totaled 105 patients with AAV, of whom 52 (40 with PR3‐ANCAs, 12 with MPO‐ANCAs) received placebo and 53 (41 with PR3‐ANCAs, 12 with MPO‐ANCAs) received belimumab; 27 of the patients were in rituximab‐induced disease remission, while 78 were in cyclophosphamide‐induced disease remission at baseline. Compared with placebo, treatment with belimumab did not reduce the risk of a PSE (adjusted hazard ratio [HR] 1.07, 95% confidence interval [95% CI] 0.44–2.59; P = 0.884) or vasculitis relapse (adjusted HR 0.88, 95% CI 0.29–2.65; P = 0.821). The overall rate of PSEs was low (11 [21.2%] of 52 patients receiving placebo, 10 [18.9%] of 53 patients receiving belimumab). Vasculitis relapse in the placebo group (n = 8) occurred independent of the induction regimen, disease stage, or ANCA type. All vasculitis relapses in the belimumab group (n = 6) occurred in patients who had PR3‐ANCA–associated vasculitis with cyclophosphamide‐induced disease remission. Adverse events occurred in 49 (92.5%) of 53 patients receiving belimumab and 43 (82.7%) of 52 patients receiving placebo, with no new safety concerns. Conclusion: Belimumab plus azathioprine and glucocorticoids for the maintenance of remission in AAV did not reduce the risk of relapse. [ABSTRACT FROM AUTHOR]

Background: In adults with active lupus nephritis, the efficacy and safety of intravenous belimumab as compared with placebo, when added to standard therapy (mycophenolate mofetil or cyclophosphamide-azathioprine), are unknown.Methods: In a phase 3, multinational, multicenter, randomized, double-blind, placebo-controlled, 104-week trial conducted at 107 sites in 21 countries, we assigned adults with biopsy-proven, active lupus nephritis in a 1:1 ratio to receive intravenous belimumab (at a dose of 10 mg per kilogram of body weight) or matching placebo, in addition to standard therapy. The primary end point at week 104 was a primary efficacy renal response (a ratio of urinary protein to creatinine of ≤0.7, an estimated glomerular filtration rate [eGFR] that was no worse than 20% below the value before the renal flare (pre-flare value) or ≥60 ml per minute per 1.73 m2 of body-surface area, and no use of rescue therapy), and the major secondary end point was a complete renal response (a ratio of urinary protein to creatinine of <0.5, an eGFR that was no worse than 10% below the pre-flare value or ≥90 ml per minute per 1.73 m2, and no use of rescue therapy). The time to a renal-related event or death was assessed.Results: A total of 448 patients underwent randomization (224 to the belimumab group and 224 to the placebo group). At week 104, significantly more patients in the belimumab group than in the placebo group had a primary efficacy renal response (43% vs. 32%; odds ratio, 1.6; 95% confidence interval [CI], 1.0 to 2.3; P = 0.03) and a complete renal response (30% vs. 20%; odds ratio, 1.7; 95% CI, 1.1 to 2.7; P = 0.02). The risk of a renal-related event or death was lower among patients who received belimumab than among those who received placebo (hazard ratio, 0.51; 95% CI, 0.34 to 0.77; P = 0.001). The safety profile of belimumab was consistent with that in previous trials.Conclusions: In this trial involving patients with active lupus nephritis, more patients who received belimumab plus standard therapy had a primary efficacy renal response than those who received standard therapy alone. (Funded by GlaxoSmithKline; BLISS-LN ClinicalTrials.gov number, NCT01639339.). [ABSTRACT FROM AUTHOR]

COPD is heterogeneous, and its presentation varies between countries. The major COPD cohort studies have only been performed in Western populations; the disease is not well characterised in other regions. The COMPASS (Investigation of the Clinical, Radiological and Biological Factors, Humanistic and Healthcare Utilisation Burden Associated with Disease Progression, Phenotypes and Endotypes of COPD in China; NCT04853225) is a prospective, 2.5-year-long, multi-centre, longitudinal, observational study with three aims: 1) to characterise stable and exacerbation phenotypes/endotypes in terms of clinical characteristics, blood and sputum biomarkers, lung microbiome and lung imaging; 2) to understand the relevance of markers of COPD disease progression identified in Western cohorts to Chinese patients; and 3) to characterise treatment pathways and healthcare resource utilisation. COMPASS will recruit 2000 participants, of which 1700 will be in Global Initiative for Chronic Obstructive Lung Disease (GOLD) Grades I-IV (n=700, 700, 200 and 100, respectively), 180 participants with chronic bronchitis without airflow limitation and 120 never-smoker healthy controls. Study visits will be at baseline, 6, 18 and 30 months and at exacerbation. Assessments include lung function, exacerbation frequency, health status, blood biomarkers and, in a sub-cohort of 400 patients, chest high-resolution computed tomography, additional blood and sputum biomarkers, airway micro-, viral- and myco-biome, and physical activity. COMPASS will establish a unique clinical and biological dataset in a well-characterised cohort of individuals with COPD in China, with a particular focus on milder patients. As the first study of its kind attempting to understand the disease in an Asian setting, it will provide valuable insights into regional and ethnic differences in COPD., Competing Interests: Conflict of interest: Z. Liang reports support for the present manuscript from GlaxoSmithKline, which funded the study (Study 208630) and National Key R&D Program of China, which supported the study (2018YFC1311900, 2017YFC1310600). The author reports other financial or nonfinancial interests as follows: key coordinator between GlaxoSmithKline and COMPASS investigators, and clinical expert for the First Affiliated Hospital of Guangzhou Medical University. Conflict of interest: N. Zhong reports support for the present manuscript from GlaxoSmithKline, which funded the study (Study 208630) and National Key R&D Program of China, which supported the study (2018YFC1311900, 2017YFC1310600). The author reports other financial or non-financial interests as follows: member of the COMPASS steering committee for GlaxoSmithKline and a medical expert for the First Affiliated Hospital of Guangzhou Medical University. Conflict of interest: R. Chen reports support for the present manuscript from GlaxoSmithKline, which funded the study (Study 208630) and National Key R&D Program of China, which supported the study (2018YFC1311900 and 2017YFC1310600). The author reports other financial or nonfinancial interests as follows: member of the COMPASS steering committee for GlaxoSmithKline and a medical expert for the First Affiliated Hospital of South University of Science and Technology of China. Conflict of interest: Q. Ma reports support for the present manuscript from GlaxoSmithKline, which funded the study (Study 208630) and National Key R&D Program of China, which supported the study (2018YFC1311900 and 2017YFC1310600). The author reports other financial or nonfinancial interests as follows: member of the COMPASS steering committee for GlaxoSmithKline and a medical expert for the North Kuanren General Hospital. Conflict of interest: Y. Sun reports support for the present manuscript from GlaxoSmithKline, which funded the study (Study 208630) and National Key R&D Program of China, which supported the study (2018YFC1311900 and 2017YFC1310600). The author reports other financial or nonfinancial interests as follows: member of the COMPASS steering committee for GlaxoSmithKline and a medical expert for Peking University Third Hospital. Conflict of interest: F. Wen reports support for the present manuscript from GlaxoSmithKline, which funded the study (Study 208630) and National Key R&D Program of China, which supported the study (2018YFC1311900 and 2017YFC1310600). The author reports other financial or nonfinancial interests as follows: member of COMPASS steering committee for GlaxoSmithKline and medical expert for West China Hospital of Sichuan University. Conflict of interest: R. Tal-Singer reports support for the present manuscript from GlaxoSmithKline, which funded the study (Study 208630) and National Key R&D Program of China, which supported the study (2018YFC1311900 and 2017YFC1310600). The author also reports that they currently hold stock of GlaxoSmithKline and a former employee of GlaxoSmithKline. Conflict of interest: B. Miller reports support for the present manuscript from GlaxoSmithKline, which funded the study (Study 208630) and National Key R&D Program of China, which supported the study (2018YFC1311900 and 2017YFC1310600). The author also reports that they currently hold stock of GlaxoSmithKline and a former employee of GlaxoSmithKline and member of COMPASS steering committee for GlaxoSmithKline. Conflict of interest: J. Yates reports support for the present manuscript from GlaxoSmithKline, which funded the study (Study 208630) and National Key R&D Program of China, which supported the study (2018YFC1311900 and 2017YFC1310600). The author also reports that they currently hold stock of GlaxoSmithKline and a former employee of GlaxoSmithKline and member of COMPASS steering committee for GlaxoSmithKline. Conflict of interest: J. Song reports support for the present manuscript from GlaxoSmithKline, which funded the study (Study 208630) and National Key R&D Program of China, which supported the study (2018YFC1311900 and 2017YFC1310600). The author also reports that they are currently an employee of GlaxoSmithKline and member of the COMPASS steering committee for GlaxoSmithKline. Conflict of interest: C. Compton reports support for the present manuscript from GlaxoSmithKline, which funded the study (Study 208630) and National Key R&D Program of China, which supported the study (2018YFC1311900 and 2017YFC1310600). The author also reports that they currently hold stock of GlaxoSmithKline and a former employee of GlaxoSmithKline and member of COMPASS steering committee for GlaxoSmithKline. Conflict of interest: B. Ji reports support for the present manuscript from GlaxoSmithKline, which funded the study (Study 208630) and National Key R&D Program of China, which supported the study (2018YFC1311900 and 2017YFC1310600). The author also reports that they currently hold stock of GlaxoSmithKline and are an employee of GlaxoSmithKline and member of COMPASS steering committee. Conflict of interest: L. Wu reports support for the present manuscript from GlaxoSmithKline, which funded the study (Study 208630) and National Key R&D Program of China, which supported the study (2018YFC1311900 and 2017YFC1310600). The author also reports that they currently employed by GlaxoSmithKline. Conflict of interest: Y. Yang reports support for the present manuscript from GlaxoSmithKline, which funded the study (Study 208630) and National Key R&D Program of China, which supported the study (2018YFC1311900 and 2017YFC1310600). The author also reports that they are currently an employee of GlaxoSmithKline. Conflict of interest: P. Jones reports support for the present manuscript from GlaxoSmithKline, which funded the study (Study 208630) and National Key R&D Program of China, which supported the study (2018YFC1311900 and 2017YFC1310600). The author also reports that they are currently an employee of GlaxoSmithKline and member of the COMPASS steering committee for GlaxoSmithKline. The author currently holds stock in GlaxoSmithKline. Conflict of interest: Jinping Zheng reports support for the present manuscript from GlaxoSmithKline, which funded the study (Study 208630) and National Key R&D Program of China, which supported the study (2018YFC1311900 and 2017YFC1310600). The author reports other financial or nonfinancial interests as follows: member of COMPASS steering committee for GlaxoSmithKline and medical expert for the First Affiliated Hospital of Guangzhou Medical University., (Copyright ©The authors 2021.)

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.)

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 10 mg/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.

Objective: This extension study of the Phase III, randomized, placebo-controlled Belimumab International SLE Study (BLISS)-52 and BLISS-76 studies allowed non-US patients with SLE to continue belimumab treatment, in order to evaluate its long-term safety and tolerability including organ damage accrual., Methods: In this multicentre, long-term extension study (GlaxoSmithKline Study BEL112234) patients received i.v. belimumab every 4 weeks plus standard therapy. Adverse events (AEs) were assessed monthly and safety-associated laboratory parameters were assessed at regular intervals. Organ damage (SLICC/ACR Damage Index) was assessed every 48 weeks. The study continued until belimumab was commercially available, with a subsequent 8-week follow-up period., Results: A total of 738 patients entered the extension study and 735/738 (99.6%) received one or more doses of belimumab. Annual incidence of AEs, including serious and severe AEs, remained stable or declined over time. Sixty-nine (9.4%) patients experienced an AE resulting in discontinuation of belimumab or withdrawal from the study. Eleven deaths occurred (and two during post-treatment follow-up), including one (cardiogenic shock) considered possibly related to belimumab. Laboratory parameters generally remained stable. The mean (s.d.) SLICC/ACR Damage Index score was 0.6 (1.02) at baseline (prior to the first dose of belimumab) and remained stable. At study year 8, 57/65 (87.7%) patients had no change in SLICC/ACR Damage Index score from baseline, indicating low organ damage accrual., Conclusion: Belimumab displayed a stable safety profile with no new safety signals. There was minimal organ damage progression over 8 years., Trial Registration: ClinicalTrials.gov, https://clinicaltrials.gov, NCT00424476 (BLISS-52), NCT00410384 (BLISS-76), NCT00732940 (BEL112232), NCT00712933 (BEL112234)., (© The Author(s) 2019. Published by Oxford University Press on behalf of the British Society for Rheumatology.)

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 10 mg/kg plus SoC or placebo plus SoC to Week 48., Results: Sixty of 707 randomized patients were enrolled from study centers in Japan (belimumab, n = 39; placebo, n = 21). 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]; p=.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 >7.5 mg/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.