PT  - JOURNAL ARTICLE
AU  - Aranow, Cynthia
AU  - Allaart, Cornelia F
AU  - Amoura, Zahir
AU  - Bruce, Ian N
AU  - Cagnoli, Patricia C
AU  - Chatham, Walter W
AU  - Clark, Kenneth L
AU  - Furie, Richard
AU  - Groark, James
AU  - Urowitz, Murray B
AU  - van Vollenhoven, Ronald
AU  - Daniels, Mark
AU  - Fox, Norma Lynn
AU  - Gregan, Yun Irene
AU  - Henderson, Robert B
AU  - van Maurik, André
AU  - Ocran-Appiah, Josephine C
AU  - Oldham, Mary
AU  - Roth, David A
AU  - Shanahan, Don
AU  - Tak, Paul P
AU  - Teng, Yk Onno
TI  - 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
AID  - 10.1136/ard-2024-225686
DP  - 2024 Nov 01
TA  - Annals of the Rheumatic Diseases
PG  - 1502--1512
VI  - 83
IP  - 11
4099  - http://ard.bmj.com/content/83/11/1502.short
4100  - http://ard.bmj.com/content/83/11/1502.full
SO  - Ann Rheum Dis2024 Nov 01; 83
AB  - 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.Data are available upon reasonable request. GSK is committed to publicly disclosing the results of GSK-sponsored clinical research that evaluates GSK medicines, and as such was involved in the decision to submit the results of this study (GSK Study 205646). Anonymised individual patient data and study documents can be requested for further research from https://www.gsk-studyregister.com/en/.