Background: B-lymphocyte stimulator (BLyS) is increased in primary Sjögren’s syndrome (pSS) and plays a role in the B-cell hyperactivity thought to contribute to pSS. Belimumab (BEL, anti-BLyS) and rituximab (RTX, anti-CD20) target B cells through distinct and potentially complementary mechanisms.

Objectives: To evaluate the safety and efficacy of subcutaneous (SC) BEL/intravenous (IV) RTX combination (BEL/RTX) in patients with pSS.

Methods: This Phase 2, double-blind study (GSK Study 201842; NCT02631538) randomised 86 adults with active pSS to 4 treatment arms stratified for baseline EULAR Sjögren’s Syndrome Disease Activity Index (ESSDAI) scores 5-12 or >12: placebo (PBO; N=13), BEL/RTX (N=24; BEL 200 mg SC weekly to Week [Wk] 24 followed by weekly PBO SC to Wk 52 + RTX 1000 mg IV, Wk 8 + 10), BEL monotherapy (N=24; BEL 200 mg SC weekly to Wk 52) or RTX monotherapy (N=25; RTX 1000 mg IV, Wk 8 + 10). Follow-up was at Wk 68. Safety to Wk 68 was the primary endpoint (safety population; patients received ≥1 dose of study treatment). Secondary/other endpoints (completer population; patients completed treatment and follow-up phase) were ESSDAI score, stimulated salivary flow, CD20+ B-cell count within salivary gland biopsies, patient-reported oral dryness, and EULAR Sjögren’s Syndrome Patient Reported Index (ESSPRI) score.

Results: Baseline demographics and disease characteristics were similar among arms. Adverse events (AEs) were balanced across arms. Serious AEs were infrequent but occurred only in active treatment arms ( Table ). No unexpected safety issues were identified with BEL/RTX relative to BEL or RTX. Treatment phase and follow-up were completed by 60/86 patients. ESSDAI reductions with BEL/RTX were numerically greater over time than PBO, with greatest difference at Wk 68 (Table), but were not differentiated from monotherapy. Stimulated salivary flow showed a trend favouring BEL/RTX vs PBO over later time points (Table). In contrast with PBO, BEL, and RTX, salivary gland biopsies from BEL/RTX showed almost complete B-cell depletion (Wk 24). There was no clear evidence for a positive effect of BEL/RTX on patient-reported oral dryness or ESSPRI score.

Conclusion: No unexpected safety issues were identified with BEL/RTX relative to BEL or RTX. BEL/RTX showed a trend towards improvement in ESSDAI and stimulated salivary flow over time, which was sustained post treatment. BEL/RTX depleted B cells in minor salivary gland biopsies.

Funding: GSK

Acknowledgements: Medical writing assistance was provided by Katalin Bartus, PhD, Fishawack Indicia Ltd., UK, part of Fishawack Health, and was funded by GSK.

Disclosure of Interests: Xavier Mariette Consultant of: BMS, Galapagos, Gilead, GSK, Janssen, Novartis, Pfizer, Servier, UCB, Grant/research support from: Servier, Chiara Baldini: None declared, Francesca Barone Consultant of: GSK, UCB, Roche, Actelion, Grant/research support from: GSK, UCB, Roche, Actelion, Employee of: Kintai therapeutics, Candel Therapeutics, Hendrika Bootsma Speakers bureau: BMS, Novartis, Consultant of: BMS, Roche, Novartis, MedImmune, UCB, Servier, Grant/research support from: BMS, Roche, Ken Clark Shareholder of: GSK, Employee of: GSK, Salvatore De Vita Consultant of: GSK, Roche, Karoline Lerang: None declared, Prafull Mistry Shareholder of: GSK, Employee of: GSK, Frederic Morin: None declared, Rajesh Punwaney Shareholder of: GSK, Employee of: GSK, Raphaèle Seror Consultant of: GSK, BMS, Fresenius Kabi, Boehringer, Jansen, Amgen, Pfizer, Roche, Paul LA van Daele: None declared, Andre van Maurik Shareholder of: GSK, Employee of: GSK, Nicolas Wisniacki Shareholder of: GSK, Employee of: GSK, David Roth Shareholder of: GSK, Employee of: GSK