Sequential Belimumab and Rituximab in SLE Save

Could disease control in active systemic lupus erythematosus (SLE) patients be improved by the sequential use of subcutaneous belimumab (BEL) and intravenous rituximab (RTX)? A double blind trial has shown that sequential BEL and RTX was not superior to BEL alone in SLE. 

This approach tests the potentially safer use of combination biologic; by using them serially rather than contemporaneously. Additionally, one of the presumed reasons why RTX failed in lupus is because it results in a high rebound in circulating BAFF (B-cell activating factor), which could be abrogated by the use of BEL).

BLISS-BELIEVE was a phase 3, double-blind trial wherein patients with active SLE initiating subcutaneous BEL 200 mg/week for 52 weeks were randomised receive either intravenous placebo (BEL/PBO) or intravenous RTX 1000 mg (BEL/RTX) at weeks 4 and 6 while stopping concomitant immunosuppressants/tapering corticosteroids; standard therapy for 104 weeks. The primary endpoin was the number of patients achieving disease control (SLE Disease Activity Index-2000 (SLEDAI-2K) ≤2; without immunosuppressants; prednisone equivalent ≤5 mg/day) at week 52.

The modified intention-to-treat analysis included 263 SLE patients. At week 52, those achieving a SLEDAI-2K < 2:

• BEL/PBO: 16.7% (12/72) 

• BEL/RTX: 19.4% (28/144) 

• OR (95% CI) 1.27 (0.60 to 2.71); p=0.5342) 

There were no significant differences in other major secondary endpoints between treatment groups, althought anti-dsDNA antibodies and B cells and B-cell subsets were lower with BEL/RTX versus BEL/PBO.  Patients receiving BEL/RTX spent more time under disease control versus BEL/PBO.

While other uncontrolled studies of sequential RTX and BEL have suggested efficacy, this trial questions the value of this combination treatment in SLE.