THU0503 PLUTO TRIAL: SENSITIVITY ANALYSES OF SRI4 RESPONSE WITH BELIMUMAB VS PLACEBO IN PAEDIATRIC PATIENTS WITH CHILDHOOD-ONSET SYSTEMIC LUPUS ERYTHEMATOSUS (CSLE)

Abstract

Background: Belimumab (BEL) is the first treatment approved in children ≥5 years of age with cSLE. This recent approval was based on favourable results of the PLUTO trial, evaluating efficacy and safety of intravenous (IV) BEL, plus standard SLE therapy (SST), vs placebo (PBO), in children with cSLE.1 Objectives: To evaluate the SLE Responder Index 4 (SRI4) sensitivity of response for the comparison of BEL vs PBO at Week (Wk) 52. Methods: In PLUTO (NCT01649765; GSK study BEL114055), an ongoing Phase 2, randomised, PBO-controlled, double-blind study, patients (pts) 5-17 years of age with active cSLE were randomised to monthly BEL 10 mg/kg IV, or PBO, plus SST, for 52 weeks. The primary efficacy endpoint was the SRI4 response rate at Wk 52. Pre-specified sensitivity analyses supporting the primary efficacy endpoint for the intention-to-treat (ITT) population included unadjusted, last observation carried forward (LOCF), completer responses, and response using SLE Disease Activity Index (SLEDAI) 2K proteinuria scoring rule (4-point score for proteinuria >0.5 g/24 h), all at Wk 52. Completers were pts who completed 52 weeks of treatment. Any pts who withdrew or received protocol-prohibited medication or a dose of allowable medication that resulted in treatment failure prior to the Wk 52 visit had missing data handled using LOCF (missing values imputed using the last previous non-missing value). Statistics are descriptive. Results: Overall, 93 pts were randomised (BEL, n=53; PBO, n=40). Majority (94.6%) of pts were female, mean (standard deviation [SD]) age was 14.0 (2.49) years and mean (SD) disease duration was 2.4 (1.93) years. By Wk 52, numerically more BEL (52.8%) than PBO (43.6%) pts were SRI4 responders; difference vs PBO 9.24; odds ratio (OR; 95% confidence interval [CI]) vs PBO 1.49 (0.64, 3.46). For each sensitivity analysis (unadjusted, LOCF, completer, and SLEDAI 2K responses) the odds of being a responder at Wk 52 were higher for pts receiving BEL vs PBO (Table). Conclusion: The results of the SRI4 primary efficacy endpoint sensitivity analyses further support a favourable effect for BEL vs PBO.