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Belimumab Injection (Benlysta)
By William T. Elliott, MD, FACP, and James Chan, PharmD, PhD. Dr. Elliott is Chair, Formulary Committee, Northern California Kaiser Permanente; and Assistant Professor of Medicine, University of California, San Francisco. Dr. Chan is Pharmacy Quality and Outcomes Manager, Kaiser Permanente, Oakland, CA. Drs. Elliott and Chan report no financial relationship to this field of study.
The FDA has approved the first new treatment for systemic lupus erythematosus (SLE) since 1955 when hydroxychloroquine and corticosteroids were approved. Belimumab is a recombinant human IgG1l monoclonal antibody specific for soluble human B lymphocyte stimulator protein (BLyS).1 It is marketed by Human Genome Sciences and GlaxoSmithKline as Benlysta.
Belimumab is indicated for the treatment of adult patients with active, autoantibody-positive, SLE who are receiving standard therapy.1
The recommended dose is 10 mg/kg at 2-week intervals for the first three doses and every 4 weeks thereafter.1 Pre-medication for prophylaxis against infusion reactions and hypersensitivity reactions should be considered.1
Belimumab is supplied as 120 mg and 400 mg single-use vials.
Patients treated with belimumab and standard therapy experienced less disease activity than those treated with standard therapy alone.1-3
African American patients and patients of African heritage do not appear to respond to belimumab.1 The response rates were less than that for placebo.
Belimumab is a human monoclonal antibody specific for BLyS. This cytokine plays an essential physiologic role in the homeostatis and survival of B-cells. BLyS is overexpressed in patients with lupus erythematosus.4 The efficacy and safety of belimumab was studied in three randomized, double-blind, placebo-controlled studies in patients with SLE according to the American College of Rheumatology criteria for systemic disease (score ≥ 6 on the Safety of Estrogens in Lupus Erythematosus National Assessment-Systemic Lupus Erythematosus Disease Activity Index [SELENA-SLEDAI]). Patients were on a stable standard of care treatment (e.g., corticosteroids, antimalarials, NSAIDs, or immunosuppressives alone or in combination). Biologics and intravenous cyclophosphamide were not permitted. Study 1 (n = 449) was a dose evaluation study while studies 2 and 3 (n = 1684) evaluated 1 mg/kg or 10 mg/kg of belimumab compared to placebo.1-3 Study 2 (BLISS-76) was 76 weeks and Study 3 (BLISS-52), 52 weeks. The primary endpoint was improvement in the Systemic Lupus Erythematosus Responder Index (SRI) defined as a reduction of at least 4 points in the SELENA-SLEDAI score, no new British Isles Lupus Assessment Group (BILAG) A organ domain score, no more than 1 new BILAG B organ domain score, and no worsening in Physician Global Assessment score. The clinical response rates (SRI) for the FDA recommended dose of 10 mg/kg were 43% for Study 1 and 58% for study 2 compared to 34% and 44%, respectively, for placebo. The combined efficacy of belimumab at week 52 was 50.6% (n = 562) vs. 38.8% (n = 563) for placebo.3 Subgroup analyses of African American patients (n = 148) showed that these patients had a lower response rate than placebo, 36% for belimumab, 10 mg/kg compared to 44% for placebo. Common adverse events (compared to placebo) include nausea (15% vs. 12%), diarrhea (12% vs. 9%), and pyrexia (10% vs. 8%). Mortality (0.9% vs. 0.4%), serious infections (6% vs. 5.2%), and depression (16% vs. 12%) were reported more frequently with belimumab compared to placebo.
SLE is a serious autoimmune disease that affects approximately 300,000 to 1.5 million Americans.5 African American women have a three times higher incidence than Caucasian women. Belimumab is the first biologic approved for the treatment of SLE and the first drug to be approved for this disease in more than a half century. While the efficacy of belimumab is encouraging, it appears to be less effective in African Americans.
1. Benlysta Prescribing Information. Human Genome Sciences. March 2011.
2. Navarra SV, et al. Lancet 2011;377:721-731.
3. Thanou-Stravraki A, Sawalha AH. Biologics: Target and Therapy 2011;5:33-43.
4. Petri M, et al. Arthritis Rheum 2008;58:2453-2459.
5. http://www.fda.gov/NewsEvents/Newroom/PressAnnouncements/ucm246489.htm. Accessed 3/11/2011.