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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: Belimumab (BEL), a monoclonal antibody targeting the B-lymphocyte stimulator, is approved in adults with active systemic lupus erythematosus (SLE). This is the first clinical trial of belimumab in pediatric patients with childhood-onset SLE (cSLE). Objectives: PLUTO, a Phase 2, randomised, double-blind trial (BEL114055; NCT01649765), evaluated the efficacy, safety and pharmacokinetics (PK) of intravenous (IV) BEL vs placebo (PBO), plus standard of care (SoC), in cSLE. Methods: Patients with cSLE 5–17 years of age were randomised to BEL 10 mg/kg IV or PBO every 4 weeks, plus SoC. Primary endpoint: SRI4 at Week 52. Major secondary endpoints: PRINTO/ACR 30 and 50 cSLE evaluation criteria for improvement at Week 52; cSLE core response variables at Week 52; and sustained SRI4 and ParentGA (patient well-being) responses (Weeks 44–52). Other endpoints: components of SRI4 at Week 52; and frequency of severe flares using the modified SELENA-SLEDAI Flare Index. Safety and PK were assessed. Analyses were performed on the intent-to-treat population. The study was not powered to test for differences between groups; p-values were not calculated. Results: 93 patients were included (BEL, n=53; PBO, n=40). Groups (BEL vs PBO) were balanced at baseline for age (mean [standard deviation] 13.5 [2.59] vs 14.8 [2.17] years, respectively) and SELENA-SLEDAI score (10.3 [3.34] vs 10.4 [3.63], respectively). Compared with PBO, there were more SRI4 responders (including all 3 components of SRI4), and PRINTO/ACR 30 and 50 responders in the BEL group (Figure). Likewise, more BEL than PBO recipients had sustained improvement of SRI and patient well-being (ParentGA) (Figure). Changes in cSLE core response variables are shown in the Table. Severe flares were 62% less frequent with BEL vs PBO (hazard ratio 0.38 [95% CI 0.18, 0.82]). PK: BEL exposures in cSLE were similar to adult SLE studies. 9/53 (17%) BEL patients had ≥1 serious adverse event vs 14/40 (35%) PBO patients. One PBO patient died of acute pancreatitis. Conclusion: The benefit:risk profile of BEL IV plus SoC in cSLE is generally consistent with BEL in adult SLE. The 10 mg/kg IV dose used in adults may be an appropriate dose in cSLE. Acknowledgement: The authors would like to acknowledge all investigators (PRINTO, PRCSG and otherwise affiliated) for the PLUTO study. Study funded by GSK. Gosia Carless, PhD, Fishawack Indicia Ltd, UK, provided editorial assistance funded by GSK. Disclosure of Interests: Nicolino Ruperto Grant/research support from: The Gaslini Hospital, where NR works as full-time public employee, has received contributions (> 10.000 USD each) from the following industries in the last 3 years: BMS, Eli-Lilly, GlaxoSmithKline, F Hoffmann-La Roche, Janssen, Novartis, Pfizer, Sobi. This funding has been reinvested for the research activities of the hospital in a fully independent manner, without any commitment with third parties., Consultant for: Received honoraria for consultancies or speaker bureaus ( I perform consultancy activities on behalf of the Gaslini Institute for the companies listed below: AbbVie, Biogen, Boehringer Ingelheim, Bristol-Myers Squibb, EMD Serono, Janssen, Novartis, Pfizer, R-Pharm. The money received for these activities are directly transferred to the Gaslini Institute’s bank account. Before March 2016, I was the head of the Pediatric Rheumatology Department at the G. Gaslini Hospital, where the PRINTO Coordinating Centre is located. For the coordination activity of the PRINTO network, the Gaslini Hospital received contributions from the industries listed in this section. This money has been reinvested for the research activities of the hospital in fully independent manners besides any commitment with third parties., Daniel J Lovell Consultant for: Consulting fees and/or honoraria from Astra Zeneca, Wyeth Pharma, Amgen, Abbott, Pfizer, F. Hoffmann-La Roche, Novartis, UBC, Takeda, GSK, Boehringer, and Celgene, Hermine Brunner Grant/research support from: Bristol-Myers Squibb, Pfizer, Consultant for: Pfizer, Bristol-Myers Squibb, Janssen, Novartis, Lilly, Roche, GlaxoSmithKline, Sanofi, Speakers bureau: Novartis, Roche