SAT0505 PLUTO TRIAL OF INTRAVENOUS BELIMUMAB IN PAEDIATRIC PATIENTS WITH CHILDHOOD-ONSET SYSTEMIC LUPUS ERYTHEMATOSUS (cSLE): PATIENT RESPONSES OVER TIME
Authors: N. Ruperto, L. Mccann, S. Takei, C. Pilkington, D. Bass, B. Ji, A. Hammer, M. Okily, G. Eriksson, H. Quasny, H. Brunner
Journal: Annals of the Rheumatic Diseases (2020)

Background: Belimumab (BEL) is a human monoclonal antibody that specifically inhibits B-cell activating factor (BAFF). PLUTO is an ongoing trial evaluating efficacy and safety of intravenous (IV) BEL in children ≥5 years of age with cSLE. Efficacy, and safety endpoints of PLUTO have been reported; 1 briefly, numerically more BEL vs PBO pts met the primary and major secondary efficacy endpoints. We present patient (pt) response to BEL over time. Objectives: To evaluate changes in SLE Responder Index (SRI) 4 and SRI6 responses, and disease activity over 52 weeks, in paediatric pts receiving BEL, or placebo (PBO), plus standard SLE therapy (SST). Methods: PLUTO (GSK Study BEL114055, NCT01649765 ) is a Phase 2, randomised, double-blind, placebo-controlled study. Pts 5–17 years of age with active cSLE were randomised to monthly BEL 10 mg/kg IV, or PBO, plus SST. Endpoints assessed: SRI4 and SRI6 response rate, mean percentage and absolute change from baseline in Safety of Estrogens in Lupus Erythematosus National Assessment (SELENA)-SLE Disease Activity Index (SLEDAI) and Physicians’ Global Assessment (PGA) scores, and percentage of pts with no new British Isles Lupus Assessment Group (BILAG) 1A/2B organ domain scores compared with baseline, all by study visit. The last-observation-carried-forward (LOCF) principle (missing values imputed using the last available non-missing value) was applied to pts who withdrew or received protocol-prohibited medication or a dose of allowable medication that resulted in treatment failure prior to the Week (Wk) 52 visit. Descriptive statistics were used. Results: A total of 93 pts (94.6% female, mean [SD] age 14.0 [2.49] years) were randomised for the intention-to-treat (ITT) population: 53 to BEL and 40 to PBO. Mean (SD) BEL and PBO baseline scores were 10.3 (3.34) and 10.4 (3.63) for SELENA-SLEDAI and 1.3 (0.43) and 1.4 (0.42) for PGA, respectively. Pt number with at least BILAG 1A/2B organ domain involvement at baseline was 37 (69.8%) for BEL and 29 (72.5%) for PBO. SRI4 and SRI6 responses over 52 weeks were mostly numerically higher with BEL than PBO; more BEL than PBO pts were SRI4 and SRI6 responders at Wk 52 ( Figure 1 ). Unadjusted mean (SE) percentage changes from baseline over time in SELENA-SLEDAI and PGA scores generally favoured BEL over PBO, as did unadjusted mean (SE) absolute changes ( Figure 2 ). Wk 52 adjusted mean (95% CI) percentage treatment difference vs PBO was -4.0% (-21.8, 13.9) for SELENA-SLEDAI and -6.1% (-23.9, 11.7) for PGA, while Wk 52 adjusted mean (95% CI) treatment difference vs PBO was -0.7 (-2.4, 1.1) for SELENA-SLEDAI and -0.1 (-0.3, 0.1) for PGA. Over the study duration, numerically more BEL than PBO pts had no new BILAG 1A/2B organ domain scores ( Figure 2 ). Figure 1. SRI4 and SRI6 response by study visit Figure 2. SELENA-SLEDAI and PGA score mean percentage and absolute change from baseline, and no new BILAG 1A/2B organ domain scores compared with baseline, all by study visit Conclusion: In line with the main analyses performed at Wk 52, 1 further analyses of responses over time in SRI4, SRI6 and disease activity generally favoured BEL over PBO. Combined, these results continue to support the efficacy profile of IV BEL in the treatment of children with cSLE. References: [1]Brunner HI, et al . Arthritis Rheumatol. 2018;70(59): 3224–5, Abst. 2867 Acknowledgments: We acknowledge all PLUTO investigators (PRINTO, PRCSG and otherwise affiliated). Study funding: GSK. Disclosure of Interests: Nicolino Ruperto Consultant of: Ablynx, AbbVie, AstraZeneca-Medimmune, Biogen, Boehringer, Bristol-Myers Squibb, Eli-Lilly, EMD Serono, GSK, Hoffmann-La Roche, Janssen, Merck, Novartis, Pfizer, R-Pharma, Sanofi, Servier, Sinergie, Sobi and Takeda, Liza McCann: None declared, Syuji Takei Grant/research support from: Eisai, Consultant of: Novartis, Bristol-Myers Squibb, Speakers bureau: GSK, Sanofi, Tanabe-Mitsubishi, Novartis, Chugai, Ono, Abbvie, Eli-Lilly, Bristol-Myers Squibb, Clarissa Pilkington: None declared, Damon Bass Shareholder of: GSK, Employee of: GSK, Beulah Ji Shareholder of: GSK, Employee of: GSK, Anne Hammer Shareholder of: GSK, Employee of: GSK, Mohamed Okily Shareholder of: GSK, Employee of: GSK, Gina Eriksson Shareholder of: GSK, Employee of: GSK, Holly Quasny Shareholder of: GSK, Employee of: GSK, Hermine Brunner Consultant of: Hoffman-La Roche, Novartis, Pfizer, Sanofi Aventis, Merck Serono, AbbVie, Amgen, Alter, AstraZeneca, Baxalta Biosimilars, Biogen Idec, Boehringer, Bristol-Myers Squibb, Celgene, EMD Serono, Janssen, MedImmune, Novartis, Pfizer, and UCB Biosciences, Speakers bureau: GSK, Roche, and Novartis