OP0135 SAFETY AND EFFICACY OF SUBCUTANEOUS BELIMUMAB AND INTRAVENOUS RITUXIMAB COMBINATION IN PATIENTS WITH PRIMARY SJÖGREN’S SYNDROME: A PHASE 2, RANDOMISED, PLACEBO-CONTROLLED 68-WEEK STUDY

Background: B-lymphocyte stimulator (BLyS) is increased in primary Sjögren’s syndrome (pSS) and plays a role the B-cell hyperactivity thought to contribute pSS. Belimumab (BEL, anti-BLyS) rituximab (RTX, anti-CD20) target B cells through distinct potentially complementary mechanisms. Objectives: To evaluate safety efficacy of subcutaneous (SC) BEL/intravenous (IV) RTX combination (BEL/RTX) patients with Methods: This Phase 2, double-blind study (GSK Study 201842; NCT02631538 ) randomised 86 adults active pSS 4 treatment arms stratified for baseline EULAR Syndrome Disease Activity Index (ESSDAI) scores 5-12 or >12: placebo (PBO; N=13), BEL/RTX (N=24; BEL 200 mg SC weekly Week [Wk] 24 followed by PBO Wk 52 + 1000 IV, 8 10), monotherapy 52) (N=25; 10). Follow-up was at 68. Safety 68 endpoint (safety population; received ≥1 dose treatment). Secondary/other endpoints (completer completed follow-up phase) were ESSDAI score, stimulated salivary flow, CD20+ count within gland biopsies, patient-reported oral dryness, Patient Reported (ESSPRI) score. Results: Baseline demographics disease characteristics similar among arms. Adverse events (AEs) balanced across Serious AEs infrequent but occurred only (Table). No unexpected issues identified relative RTX. Treatment phase 60/86 patients. reductions numerically greater over time than PBO, greatest difference (Table), not differentiated from monotherapy. Stimulated flow showed trend favouring vs later points In contrast BEL, RTX, biopsies almost complete depletion (Wk 24). There no clear evidence positive effect on dryness ESSPRI Table 1. Key selected – population (N=13 (N=24 (N=25 AEs, n (%) 13 (100) 23 (96) Drug-related 10 (77) 17 (71) 16 (67) 14 (56) leading discontinuation/withdrawal, 1 (8) 5 (21) 3 (13) (20) SAEs, 0 2 (16) Number SAEs 7 Deaths, (4)* Infections Infestations, † 11 (85) 19 (79) 21 (88) 18 (72) Efficacy completer (N=8 (N=17 (N=19 (N=16 change, LS mean (SE) BL ‡ 12 -2.00 (1.449) -4.85 (0.996) -3.87 (0.949) -4.22 (1.048) § -2.87 (1.324) -5.32 (0.911) (0.869) -5.25 (0.940) (1.294) -5.67 (0.890) -4.76 (0.850) -4.32 (0.919) -1.75 (1.400) -5.73 (0.962) (0.918) -4.38 (0.994) (ml/min), (SD) 0.47 (0.247) 0.71 (0.629) 0.43 (0.329) 0.62 (0.621) 0.49 (0.205) 0.75 (0.834) (0.373) 0.58 (0.527) 0.55 (0.305) 0.78 (0.790) 0.45 (0.411) 0.72 0.53 (0.378) 1.00 (1.146) (0.608) 0.69 (0.781) 0.36 (0.163) 0.88 (0.817) 0.52 (0.450) 0.73 (0.785) *Aspiration (n=1); considered related treatment; patient died food aspiration; System organ class highest percent AEs; Analysis performed using mixed model repeated measures; n=15. BL, baseline; LS, Least square; serious SD, standard deviation; SE, error Conclusion: towards improvement time, which sustained post treatment. depleted minor biopsies. Funding: GSK Acknowledgements: Medical writing assistance provided Katalin Bartus, PhD, Fishawack Indicia Ltd., UK, part Health, funded GSK. Disclosure Interests: Xavier Mariette Consultant of: BMS, Galapagos, Gilead, GSK, Janssen, Novartis, Pfizer, Servier, UCB, Grant/research support from: Chiara Baldini: None declared, Francesca Barone Roche, Actelion, Employee Kintai therapeutics, Candel Therapeutics, Hendrika Bootsma Speakers bureau: MedImmune, Ken Clark Shareholder Salvatore De Vita Karoline Lerang: Prafull Mistry Frederic Morin: Rajesh Punwaney Raphaèle Seror Fresenius Kabi, Boehringer, Jansen, Amgen, Paul LA van Daele: Andre Maurik Nicolas Wisniacki David Roth