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Background Belimumab is approved as add-on therapy for patients ≥5 years with active, autoantibody-positive systemic lupus erythematosus (SLE).1 The PLUTO trial (NCT01649765) demonstrated safety and efficacy of belimumab in children with SLE2 as generally consistent with adult studies. The current analysis assessed the efficacy of belimumab 10 mg/kg given intravenously (IV) to patient subgroups with baseline markers of high disease activity in PLUTO versus pooled BLISS-52 (NCT00424476) and BLISS-76 (NCT00410384) SLE trials. Methods Patients 5–17 years (PLUTO) and ≥18 years (BLISS-52 and BLISS-76) with active SLE were randomised to IV belimumab 10 mg/kg or placebo, plus standard of care (SoC) (PLUTO);2 and IV belimumab 10 mg/kg, or placebo, plus SoC (BLISS trials).3 The primary endpoint was SLE Responder Index 4 (SRI4) at Week 52. This post hoc across-trial comparison (intention-to-treat [ITT] population) investigated the treatment effect of belimumab according to baseline disease activity indicators (Safety of Estrogens in Lupus Erythematosus National Assessment-SLE Disease Activity Index [SELENA-SLEDAI] score, anti-dsDNA and complement C3/C4 levels) and steroid use; analyses were descriptive. Results In PLUTO, belimumab demonstrated higher SRI4 response versus placebo; this response was similar for patients with baseline SELENA-SLEDAI scores of ≥10 and ≤9, and for and those receiving steroids, but greater in those with scores ≥13, low anti-dsDNA, or normal/high C3/C4 (table 1). Subgroup analyses from the BLISS adult studies demonstrated similar findings with the exception of patients with high anti-dsDNA or low C3/C4 (table 1). Conclusions Subgroup analyses from the PLUTO trial demonstrated favourable belimumab responses in paediatric patients with high SELENA-SLEDAI scores, similar to those observed in adult belimumab studies. However, these results should be interpreted with caution due to the small sample size of PLUTO, the post hoc nature of the analyses and other limitations. Disclosures DLB, MO, AH, BJ, DR and HQ are employees of GSK. BJ and DLB hold stocks and shares in GSK; MO, AH, DR and HQ hold shares in GSK. Acknowledgements This study was funded by GSK. Medical writing support was provided by Gosia Carless, PhD, Fishawack Indicia Ltd, UK, and was funded by GSK. References Benlysta US prescribing information. GlaxoSmithKline; 2018. Available at: https://www.gsksource.com/pharma/content/dam/GlaxoSmithKline/US/en/Prescribing_Information/Benlysta/pdf/BENLYSTA-PI-MG-IFU-COMBINED.PDF Brunner H.I., Abud-Mendoza C., Viola D.I., Calvo I., Levy D.M., Calderon Gallegos J., et al. Efficacy and safety of intravenous belimumab in children with systemic lupus erythematosus. Arthritis Rheumatol 2018;70(59):3224–3225, Abstract 2867. van Vollenhoven R.F., Petri M.A., Cervera R., Roth D.A., Ji B.N., Kleoudis, et al. Belimumab in the treatment of systemic lupus erythematosus: high disease activity predictors of response. Ann Rheum Dis 2012; 71:1343–1349.

Background Black patients have an increased prevalence and severity of systemic lupus erythematosus (SLE), alongside higher mortality rates. The efficacy and safety of intravenous (IV) belimumab has been demonstrated in several Phase 2/3 studies; however, the small number of black patients within these trials, and the conflicting results, have limited conclusions regarding efficacy in this population. The objective of this study was to specifically assess the efficacy and safety of IV belimumab plus standard of care (SoC) in black patients with active, auto antibody-positive SLE. Methods EMBRACE (NCT01632241) is a randomized, multicenter, double-blind, placebo-controlled trial in patients of self identified black race, aged 18 years, with active SLE at screening. Patients were randomized (2:1) to monthly belimumab 10 mg/kg IV or placebo, plus SoC. The primary endpoint was the SLE Responder Index (SRI) response rate with modified SLEDAI-2K (S2K) scoring for proteinuria at Week 52 (SRI-S2K response required a 4 point reduction in the SELENA-SLEDAI (SS)-S2K, no worsening [increase of Results The mITT population comprised 448 patients; 96.9% were female and mean (SD) age was 38.8 (11.42) years. Although the study did not achieve the primary endpoint, numerical trends were observed in favor of belimumab, and significant improvements were observed in subgroups with characteristics of high disease activity (HDA; table). Study withdrawals were similar between groups (belimumab 22.4%; placebo 24.2%) and AEs were the primary reason for withdrawals (belimumab 5.4%; placebo 6.7%). The percentage of patients who experienced an AE (belimumab 83.7%; placebo 87.3%) or serious AE (belimumab 10.9%; placebo 18.8%) was similar between groups. Two deaths occurred within the belimumab group (0.6%; pneumonia and meningitis); neither were established as directly related to belimumab. Conclusions Whilst the primary endpoint of this study in black patients with SLE was not achieved, improvements in favor of belimumab were observed, with significant benefits in patients with HDA. The safety profile was acceptable and consistent with previous studies. Funding Source(s): Study (BEL115471) funded by GSK.

Background and aims Steroid reduction is an important treatment goal in systemic lupus erythematosus (SLE). The steroid-sparing effects of belimumab were investigated in subjects in North East Asia. Methods This multicentre, 52 week study (1 13 750/NCT01345253) randomised (2:1) subjects (≥18 years) with SELENA-SLEDAI ³8 to intravenous belimumab 10 mg/kg or placebo every 28 days, plus standard SLE therapy. Multiple measures of steroid use (prednisone equivalent) were made, including a secondary endpoint of reduction in dose over 52 weeks among subjects receiving >7.5 mg/day at baseline (number of days≤7.5 mg/day and/or dose reduced by 50% from baseline). The primary endpoint was SLE Responder Index response rate at Week 52 (reported elsewhere). Results Baseline prednisone doses were similar between groups (Table 1). Across the population, cumulative prednisone dose over 52 weeks was significantly lower in the belimumab group versus placebo (p=0.0005; Table 1. For subjects with baseline dose >7.5 mg/day, the median number of days that prednisone dose was ≤7.5 mg/day and/or reduced by 50% was zero in both groups; however, the 75 th percentile was larger for belimumab (213.5 days) versus placebo (172.0), reflecting the subjects who achieved longer durations of reduced steroid use within the belimumab group (p=0.0288; Figure 1). More subjects in the belimumab group had a dose reduction of ≥25% to ≤7.5 mg/day during Weeks 40–52 (belimumab, 15.6%; placebo, 10.9%: p=0.0721). Adverse event incidences were similar (belimumab, 75.7%; placebo, 74.9%). Conclusions These results suggest belimumab is more effective than placebo in reducing steroid use across 52 weeks in this population. Study funded by GSK.