BELIMUMAB INCREASES SRI-4 RESPONSE RATES VERSUS PLACEBO IN EARLY ACTIVE SYSTEMIC LUPUS ERYTHEMATOSUS: A LARGE INTEGRATED ANALYSIS OF BELIMUMAB TRIALS

Background: There are demonstrated benefits of early introduction of treatment for autoimmune diseases; however, data are not available for patients with systemic lupus erythematosus (SLE) as there is no clear definition of early disease. Improved understanding of early treatment is relevant, with updated EULAR recommendations for SLE management to consider biologics in patients unresponsive to hydroxychloroquine (+/- glucocorticoids [GC]) or those unable to reduce GCs. In advance of robust, prospective data evaluating earlier biologic use, pooled analyses of belimumab (BEL) data from registrational clinical trials may provide insights. Objectives: To use pooled data from BEL clinical trials to evaluate the effect of BEL versus placebo (PBO) plus standard therapy (ST) on the SLE Responder Index (SRI)-4 in patients with active SLE across early and established disease subgroups, defined based on patients’ baseline SLE disease duration (<2 or ≥2 years), baseline Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI) score (0 or ≥1) and baseline immunosuppressant (IS) use (no or yes). Methods: This post hoc analysis integrated data from five international Phase 3 BEL trials in adults with active SLE, published over the course of ~10 years (BLISS-76, BLISS-52, North East Asia, EMBRACE [patients with Black African ancestry] and BLISS-SC). Included patients were randomised to BEL (10 mg/kg/month intravenously or 200 mg/week subcutaneously) or PBO, plus ST. SRI-4 responses at Week 52 with BEL versus PBO, plus ST, were evaluated in subgroup analyses representing early disease (baseline SLE disease duration <2 years; baseline SDI=0; no baseline IS use) and established disease (baseline SLE disease duration ≥2 years; baseline SDI≥1; baseline IS use). Logistic regression models were used to estimate odds ratios (OR), 95% confidence intervals (CI) and p values for the comparisons of BEL versus PBO with covariates for treatment group, study, and baseline Safety of Estrogens in Lupus Erythematosus National Assessment–SLE Disease Activity Index (SELENA-SLEDAI) score (≤9 vs ≥10). Results: In total 3086 patients (BEL, n=1869; PBO, n=1217) were included in the analysis. Differences in baseline characteristics were observed between subgroups for some parameters (Table 1). Significantly more patients achieved an SRI-4 response at Week 52 with BEL versus PBO in the pooled population (OR [95% CI]: 1.70 [1.46, 1.98], p<0.0001), and regardless of baseline SLE disease duration (<2 years: 1.38 [1.05, 1.83], p=0.0219; ≥2 years: 1.85 [1.54, 2.22], p<0.0001), SDI score at baseline (SDI=0: 1.56 [1.29, 1.89]; SDI≥1: 1.95 [1.50, 2.54]; both p<0.0001) or baseline IS use (no: 1.63 [1.31, 2.03]; yes: 1.77 [1.43, 2.18]; both p<0.0001; Table 2). The observed proportion of SRI-4 responders was higher in all three early disease subgroups for both BEL (57–58%) and PBO (45–48%), compared with the pooled population (BEL, 55%; PBO, 42%) and the established disease subgroups (BEL, 51–54%; PBO, 35–39%; Table 2). Conclusion: This post hoc analysis in a large, pooled dataset further confirmed the efficacy of BEL versus PBO across all early and established disease subgroups, defined based on baseline SLE disease duration, extent of organ damage or baseline IS use. Patients with early disease had higher responses than those with established disease, but with smaller treatment differences. These trials were not designed to evaluate SRI-4 response in an early SLE population; however, data support that use of BEL in early disease may improve outcomes. Longer, prospective studies in a population of patients with early SLE would be needed to confirm these findings. REFERENCES: [1] Fanouriakis A, et al Ann Rheum Dis 2024;83:15 [2] Navarra SV, et al Lancet 2011;377:721 [3] Furie R, et al Arthritis Rheum 2011;63(12):3918 [4] Zhang F, et al Ann Rheum Dis 2018;77:355 [5] Stohl W, et al Arthritis Rheum 2017;69(5):1016 [6] Ginzler E, et al Arthritis Rheum 2022;74(1):112 Acknowledgements: This analysis was funded by GSK. Editorial support (GSK-funded): Evelin O. Szalai, Fishawack Indicia Ltd, UK, part of Avalere Health. Disclosure of Interests: Karen Costenbader GSK, BMS, AstraZeneca, Cabaletta Bio, Exagen Diagnostics, Merck, Gilead, Joan Merrill AbbVie, BMS, Sanofi/Provention, RemeGen, Takeda, Xencor, Yes for CME compliant talks. AbbVie, AstraZeneca, Aurinia, BMS, GSK, AbbVie, Amgen, AstraZeneca, Aurinia, BMS, GSK, EMD Serono, Genentech, Gilead, Kezar, Lilly, MSD, Pfizer, Sanofi/Provention, RemeGen, Takeda, UCB, Xencor, Zenas, AstraZeneca, BMS, GSK, Marta Mosca GSK, AstraZeneca, Otsuka, Janssen, AbbVie, Lilly, GSK, AstraZeneca, Otsuka, UCB, AbbVie, Idorsia, GSK, Holly A. Quasny GSK, GSK, Christine Henning GSK, GSK, Steven Bloom GSK, Julia H. N. Harris GSK, GSK, Ciara O’Shea GSK, GSK, Tatsuya Atsumi AbbVie Inc., Alexion Inc., Asahi-Kasei Co,. Astellas Pharma Inc., AstraZeneca plc., Bayer Yakuhin, Bristol-Myers Squibb Co., Chugai Pharmaceutical Co., Ltd., Daiichi Sankyo Co., Ltd., Eisai Co. Ltd., Eli Lilly Japan K.K., Gilead Sciences K.K., GlaxoSmithKline K.K, Janssen Pharmaceutical K.K., Novartis Pharma K.K., Nippon Boehringer Ingelheim Co., Ltd., Mitsubishi Tanabe Pharma Co., Pfizer Inc., Taiho Pharmaceutical Co., Ltd. and UCB Japan Co. Ltd., GlaxoSmithKline K.K, AstraZeneca plc., Nippon Boehringer Ingelheim Co., Ltd., Novartis Pharma K.K., Otsuka Pharmaceutical Co., Ltd, GlaxoSmithKline K.K, Ronald F. van Vollenhoven AstraZeneca, Galapagos, MSD, Novartis, Pfizer, Roche, Sanofi, UCB, AbbVie, AstraZeneca, BMS, Galapagos, GSK, Janssen, Pfizer, UCB, AbbVie, AstraZeneca, Biogen, BMS, Galapagos, GSK, Janssen, Pfizer, RemeGen, UCB, BMS, UCB. DOI: 10.1136/annrheumdis-2024-eular.1835 Keywords: Outcome measures, Randomized controlled trial, Biological DMARD Citation: , volume 83, supplement 1, year 2024, page 966Session: Systemic lupus erythematosus (Poster View)

Outcome measures, Randomized controlled trial, Biological DMARD