A phase III, randomized, placebo-controlled study of belimumab, a monoclonal antibody that inhibits B lymphocyte stimulator, in patients with systemic lupus erythematosus
2011/09/01 by Richard Furie, Michelle Petri, Omid Zamani +18 · 31 citations
Medicine · #Systemic Lupus Erythematosus Research #Multiple Sclerosis Research Studies #Liver Diseases and Immunity
paper · doi:10.1002/art.30613
Abstract
OBJECTIVE: To assess the efficacy/safety of the B lymphocyte stimulator inhibitor belimumab plus standard therapy compared with placebo plus standard therapy in active systemic lupus erythematosus (SLE). METHODS: In a phase III, multicenter, randomized, placebo-controlled trial, 819 antinuclear antibody-positive or anti-double-stranded DNA-positive SLE patients with scores ≥6 on the Safety of Estrogens in Lupus Erythematosus National Assessment (SELENA) version of the SLE Disease Activity Index (SLEDAI) were randomized in a 1:1:1 ratio to receive 1 mg/kg belimumab, 10 mg/kg belimumab, or placebo intravenously on days 0, 14, and 28 and then every 28 days for 72 weeks. The primary efficacy end point was the SLE Responder Index (SRI) response rate at week 52 (an SRI response was defined as a ≥4-point reduction in SELENA-SLEDAI score, no new British Isles Lupus Assessment Group [BILAG] A organ domain score and no more than 1 new BILAG B score, and no worsening in physician's global assessment score versus baseline). RESULTS: Belimumab at 10 mg/kg plus standard therapy met the primary efficacy end point, generating a significantly greater SRI response at week 52 compared with placebo (43.2% versus 33.5%; P = 0.017). The rate with 1 mg/kg belimumab was 40.6% (P = 0.089). Response rates at week 76 were 32.4%, 39.1%, and 38.5% with placebo, 1 mg/kg belimumab, and 10 mg/kg belimumab, respectively. In post hoc sensitivity analyses evaluating higher SELENA-SLEDAI score thresholds, 10 mg/kg belimumab achieved better discrimination at weeks 52 and 76. Risk of severe flares over 76 weeks (based on the modified SLE Flare Index) was reduced with 1 mg/kg belimumab (34%) (P = 0.023) and 10 mg/kg belimumab (23%) (P = 0.13). Serious and severe adverse events, including infections, laboratory abnormalities, malignancies, and deaths, were comparable across groups. CONCLUSION: Belimumab plus standard therapy significantly improved SRI response rate, reduced SLE disease activity and severe flares, and was generally well tolerated in SLE.
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- Pathogenesis of autoimmune disease
- B cell-targeted therapies in systemic lupus erythematosus
- The discovery and development of belimumab: the anti-BLyS-lupus connection. [europepmc]
- Belimumab reduces autoantibodies, normalizes low complement levels, and reduces select B cell populations in patients with systemic lupus erythematosus. [europepmc]
- Taming lupus-a new understanding of pathogenesis is leading to clinical advances. [europepmc]
- The pathogenesis of systemic lupus erythematosus-an update. [europepmc]
- Unmet medical needs in systemic lupus erythematosus. [europepmc]
- Clinical targeting of the TNF and TNFR superfamilies. [europepmc]
- The BAFF/APRIL system: emerging functions beyond B cell biology and autoimmunity. [europepmc]
- Plasma B lymphocyte stimulator and B cell differentiation in idiopathic pulmonary fibrosis patients. [europepmc]
- Type I interferon in the pathogenesis of lupus. [europepmc]
- Measuring therapeutic response in chronic graft-versus-host disease. National Institutes of Health consensus development project on criteria for clinical trials in chronic graft-versus-host disease: IV. The 2014 Response Criteria Working Group report. [europepmc]
- Approaches for estimating minimal clinically important differences in systemic lupus erythematosus. [europepmc]
- Measuring disease activity in adults with systemic lupus erythematosus: the challenges of administrative burden and responsiveness to patient concerns in clinical research. [europepmc]
- Beyond TNF: TNF superfamily cytokines as targets for the treatment of rheumatic diseases. [europepmc]
- Pathogenesis of Human Systemic Lupus Erythematosus: A Cellular Perspective. [europepmc]
- A pivotal phase III, randomised, placebo-controlled study of belimumab in patients with systemic lupus erythematosus located in China, Japan and South Korea. [europepmc]
- Targeting B Cells and Plasma Cells in Autoimmune Diseases. [europepmc]
- BAFF and BAFF-Receptor in B Cell Selection and Survival. [europepmc]
- Systemic lupus erythematosus: Diagnosis and clinical management. [europepmc]
- The Expanding Field of Secondary Antibody Deficiency: Causes, Diagnosis, and Management. [europepmc]
- B Cell Abnormalities in Systemic Lupus Erythematosus and Lupus Nephritis-Role in Pathogenesis and Effect of Immunosuppressive Treatments. [europepmc]
- Systemic Lupus Erythematosus (SLE) Therapy: The Old and the New. [europepmc]
- Safety and efficacy of intravenous belimumab in children with systemic lupus erythematosus: results from a randomised, placebo-controlled trial. [europepmc]
- New insights into the role of antinuclear antibodies in systemic lupus erythematosus. [europepmc]
- B cell depletion therapies in autoimmune disease: advances and mechanistic insights. [europepmc]
- Pathogenesis of autoimmune disease. [europepmc]
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