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
Authors: X. Mariette et al.
B-lymphocyte stimulator (BLyS) is increased in primary Sjögren’s syndrome (pSS) and plays a role in its B-cell hyperactivity. Belimumab (BEL, anti-BLyS) and rituximab (RTX) target B cells by potentially complementary mechanisms.
This Phase 2, double-blind study randomised 86 adults with active pSS to 4 treatment arms stratified for baseline Sjögren’s Syndrome Activity. Arm 1: placebo (PBO; N=13). Arm 2: BEL/RTX (N=24; BEL 200 mg SC weekly to week 24 + RTX 1000 mg IV, week 8 + 10., Arm 3: BEL monotherapy (N=24; BEL 200 mg SC weekly to week 52). Arm 4: RTX monotherapy (N=25; RTX 1000 mg IV, week 8 + 10). Follow-up was at week 68.
Adverse events (AEs) were balanced across arms. Serious AEs were infrequent but occurred only in active treatment arms. ESSDAI reductions with BEL/RTX were numerically greater over time than PBO, with greatest difference at week 68 (Table), but were not different from monotherapy. Stimulated salivary flow showed a trend favouring BEL/RTX vs PBO. In contrast with PBO, BEL, and RTX, salivary gland biopsies from BEL/RTX showed almost complete B-cell depletion at week 24. There was no clear evidence for a positive effect of BEL/RTX on patient-reported oral dryness or ESSPRI score.
Targeting B-cells dually by the RTX/BEL drug combination demonstrated a trend towards improved pSS activity and salivary flow, along with B-cell depletion in minor salivary gland biopsies. Larger studies must determine if patients benefit long-term in this difficult-to-treat connective tissue disease.