Belimumab: review of use in systemic lupus erythematosus.

Background: Belimumab, a monoclonal antibody that inhibits B-lymphocyte stimulating protein, was the first biologic agent approved for, and the first drug approved in 55 years for, the treatment of systemic lupus erythematosus (SLE) by the US Food and Drug Administration (FDA).

Objective: This article reviews the current research on belimumab and provides recommendations on its use in the treatment of SLE.

Methods: The Cochrane Library, EBSCO, IPA, MEDLINE, and SCOPUS were searched for research published from January 2000 to November 2011, using the search terms belimumab, Benlysta, and Lympho-Stat B. Selection criteria included peer-reviewed original research articles on the pharmacology, pharmacokinetic properties, drug interactions, and clinical efficacy and tolerability of belimumab in the treatment of SLE. Abstracts from the annual meetings of major rheumatology medical organizations and societies were searched and reviewed for new content. Additional information on belimumab was obtained from the manufacturer, from the FDA, and from other sources. MEDLINE was also used to select clinical studies and therapeutic guidelines on SLE therapy.

Results: The literature search identified 1 Phase II and 2 Phase III studies that compared belimumab (1, 4, and 10 mg/kg/dose IV on days 0, 14, and 28; then every 28 days) to placebo in patients with active SLE on concurrent therapies. Patients with active lupus nephritis or neuropsychiatric lupus were excluded. In a Phase II, 52-week study, 24-week mean Safety of Estrogens in Lupus Erythematosus National Assessment-Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI) scores were decreased by 19.5% with belimumab versus 17.2% with placebo (P = NS). Median time to first flare was 67 days with belimumab versus 83 days with placebo (P = NS). In seropositive patients, 52-week mean SELENA-SLEDAI scores were decreased by 28.8% with belimumab versus 14.2% with placebo (P < 0.05), and physician's global assessment scores were improved by 32.7% with belimumab versus 10.7% with placebo (P < 0.05). Two Phase III studies were performed in seropositive SLE patients. In a Phase III, 52-week study, the rates of response (a reduction of ≥4 points on the SLE Response Index [SRI]) at week 52 were 51% and 58% with belimumab 1 and 10 mg/kg/dose, respectively, versus 44% with placebo (both, P < 0.05). In a Phase III, 76-week study, the rates of response, as measured using SRI, at week 52 were 42.8% and 46.5% with belimumab 1 and 10 mg/kg/dose versus 35.3% with placebo (P = NS and P < 0.001); at 76 weeks, response rates were 42.1% and 41.4% with belimumab 1 and 10 mg/kg/dose versus 33.8% with placebo (P < 0.05 and P = NS). The tolerability data from these studies did not suggest any overall differences between belimumab and placebo.

Conclusions: Based on the findings from the present review, belimumab appears to be efficacious and generally well-tolerated and in the treatment of SLE other than lupus nephritis or neuropsychiatric lupus. Additional clinical and economics studies are needed to determine the most appropriate place for belimumab in the treatment of SLE.