Journal Article

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

Aranow, Cynthia, van Maurik, André, van Vollenhoven, Ronald, Henderson, Robert B, Furie, Richard, Teng, Yk Onno, Amoura, Zahir, Cagnoli, Patricia C, Bruce, Ian N, Shanahan, Don, Roth, David A, Clark, Kenneth L, Groark, James, Urowitz, Murray B, Tak, Paul P, Fox, Norma Lynn, Allaart, Cornelia F, Chatham, Walter W, Ocran-Appiah, Josephine C, Gregan, Yun Irene, Daniels, Mark, Oldham, Mary

2024

Overview

ObjectivesDisease 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).MethodsIn 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.ResultsThe 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.ConclusionsBEL/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.

• Publisher: BMJ Publishing Group Ltd and European League Against Rheumatism,Elsevier Limited,BMJ Publishing Group
• Subject: Adult / Anti-DNA antibodies / Antibodies, Antinuclear - blood / Antibodies, Monoclonal, Humanized - administration & dosage / Antibodies, Monoclonal, Humanized - therapeutic use / Antirheumatic Agents - administration & dosage / Antirheumatic Agents - therapeutic use / Autoimmune Diseases / B-Lymphocytes / Biological Therapy / Biomarkers / Clinical Science / Clinical trials / Corticosteroids / Disease control / Double-Blind Method / Drug Administration Schedule / Drug Therapy, Combination / Female / Humans / Immunosuppressive agents / Immunosuppressive Agents - administration & dosage / Immunosuppressive Agents - therapeutic use / Immunotherapy / Injections, Subcutaneous / Intravenous administration / Lupus / Lupus Erythematosus, Systemic / Lupus Erythematosus, Systemic - drug therapy / Lupus Erythematosus, Systemic - immunology / Lymphocytes B / Male / Middle Aged / Monoclonal antibodies / Patients / Placebos / Prednisone / Remission / Remission (Medicine) / Remission Induction / Rituximab / Rituximab - administration & dosage / Rituximab - adverse effects / Rituximab - therapeutic use / Severity of Illness Index / Statistical analysis / Steroids / Systemic Lupus Erythematosus / Treatment Outcome