Efficacy and Safety of Sequential Therapy with Subcutaneous Belimumab and One Cycle of Rituximab in Patients with Systemic Lupus Erythematosus: the Phase 3, Randomised, Placebo-controlled BLISS-BELIEVE Study

Overview

Journal Ann Rheum Dis

Specialty Rheumatology

Date 2024 Aug 19

PMID 39159997

Authors

Cynthia Aranow

Cornelia F Allaart

Zahir Amoura

Ian N Bruce

Patricia C Cagnoli

Walter W Chatham

Kenneth L Clark

Richard Furie

James Groark

Murray B Urowitz

Ronald van Vollenhoven

Mark Daniels

Norma Lynn Fox

Yun Irene Gregan

Robert B Henderson

Andre van Maurik

Josephine C Ocran-Appiah

Mary Oldham

David A Roth

Don Shanahan

Paul P Tak

Yk Onno Teng

Affiliations

Soon will be listed here.

Abstract

Objectives: Disease activity control in patients with systemic lupus erythematosus (SLE) with corticosteroid and immunosuppressant withdrawal is a treatment goal. We evaluated whether this could be attained with sequential subcutaneous belimumab (BEL) and one cycle of rituximab (RTX).

Methods: In this phase 3, double-blind BLISS-BELIEVE trial (GSK Study 205646), patients with active SLE initiating subcutaneous BEL 200 mg/week for 52 weeks were randomised to 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 (BEL/ST; reference arm) was included.

Primary Endpoint: proportion of patients achieving disease control (SLE Disease Activity Index-2000 (SLEDAI-2K) ≤2; without immunosuppressants; prednisone equivalent ≤5 mg/day) at week 52 with BEL/RTX versus BEL/PBO. Major (alpha-controlled) secondary endpoints: proportion of patients with clinical remission (week 64; clinical SLEDAI-2K=0, without immunosuppressants/corticosteroids); proportion of patients with disease control (week 104). Other assessments: disease control duration, anti-dsDNA antibody, C3/C4 and B cells/B-cell subsets.

Results: The modified intention-to-treat population included 263 patients. Overall, 16.7% (12/72) of BEL/PBO and 19.4% (28/144) of BEL/RTX patients achieved disease control (OR (95% CI) 1.27 (0.60 to 2.71); p=0.5342) at week 52. For major secondary endpoints, differences between BEL/RTX and BEL/PBO were not statistically significant. Anti-dsDNA antibodies and most assessed B cells/B-cell subsets were lower with BEL/RTX versus BEL/PBO. Mean disease control duration through 52 weeks was significantly greater with BEL/RTX versus BEL/PBO.

Conclusions: BEL/RTX showed no superiority over BEL/PBO for most endpoints analysed; however, it led to significant improvements in disease activity markers compared with BEL/PBO. Further investigation of combination treatment is warranted.

Trial Registration Number: NCT03312907.

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