Belimumab intravenous injection (Benlysta): IV injection for the treatment of adult patients with active autoantibody-positive systemic lupus erythematosus already receiving standard therapy

Systemic lupus erythematosus (SLE) is a serious, potentially fatal, autoimmune disease that affects the joints, skin, kidneys, lungs, heart, and the brain. On March 9, 2011, FDA approved belimumab intravenous injection for the treatment of adult patients with active, autoantibody-positive SLE who are currently receiving standard therapy.

Efficacy. Belimumab's efficacy was evaluated in 3 randomized controlled studies involving patients with SLE receiving standard treatment with corticosteroids, anti-malarials, non-steroidal anti-inflammatory drugs, and immunosuppressive agents. The studies excluded patients who had received prior B-cell targeted therapy or intravenous cyclophosphamide, as well as those with active lupus involving the kidneys or central nervous system. The first study of the 3 studies was integral in identifying the target population of autoantibody-positive SLE patients. The 2 subsequent studies randomly assigned a total of 1,684 patients with autoantibody-positive, active disease [defined as a SELENA-SLEDIA score ≥6 (an objective measure in global disease activity)] to receive belimumab 1 mg/kg or 10 mg/kg plus standard therapy or placebo plus standard therapy. In both trials the proportion of patients responding to therapy was significantly higher in the belimumab 10-mg/kg group than the placebo group (study 1: OR=1.5; 95% CI, 1.1–2.2 and study 2: OR=1.8, 95% CI, 1.3–2.6). There was no statically significant difference in response rate between patients receiving belimumab 1 mg/kg and placebo. In exploratory subgroup analysis, the response rate in African-American patients was less with belimumab 10 mg/kg (36%) than in those receiving placebo (44%).

Safety. The most commonly reported adverse reactions were nausea, diarrhea, pyrexia, nasopharyngitis, bronchitis, insomnia, pain in extremity, depression, migraine, and pharyngitis. In these studies, a greater number of deaths were reported with belimumab than with placebo, with a total of 14 deaths occurring during the treatment periods. Explanations for these deaths included infection, cardiovascular disease, and suicide; however, no single cause predominated. Patients being treated for a chronic infection should not begin therapy with belimumab, as serious infections have been reported. Psychiatric events (eg, depression) were reported more frequently in the belimumab groups compared to placebo. As with other immunomodulating agents, belimumab may increase the risk of malignancy.