PHARMACODYNAMIC EFFECT OF SEQUENTIAL BELIMUMAB (BEL) AND RITUXIMAB (RTX) THERAPY IN PATIENTS (PTS) WITH SYSTEMIC LUPUS ERYTHEMATOSUS (SLE): THE PHASE 3, RANDOMISED, PLACEBO-CONTROLLED BLISS-BELIEVE STUDY
Authors: Y.K.O. Teng et al.
Belimumab is approved for active SLE and lupus nephritis. Despite failed trials, rituximab remains in the SLE treatment armamentarium. Sequential BEL and RTX therapy offers a promising strategy to target B cells by distinct but complementary mechanisms.
To assess the pharmacodynamic effects of BEL and a single RTX cycle on immunologic biomarkers in adults with SLE.a 104-week randomized study on patients with active SLE was conducted. All patients received s.c. belimumab 200 mg/wk for 52 wks and were then randomised to receive either rituximab 1000 mg at wks 4 + 6 (BEL/RTX), placebo at wks 4 + 6 (BEL/PBO), or continued treatment with standard therapy (BEL/ST).
At wk 52, reductions under Benlysta in anti-dsDNA levels were seen in all 3 groups with a significant difference between BEL/RTX and BEL/PBO (p=0.0495). C3/C4 levels increased from BL to wks 52 and 104 in all groups, with trends for greater increases with BEL/RTX versus BEL/PBO.
Similar to previous reports in Sjögren’s syndrome, it is now shown in patients with active SLE that targeting B-cells dually by the RTX/BEL combination reduces serological SLE activity. So far unpublished clinical endpoints and safety data must, however, determine if patients benefit long-term.