Current Pharmaceutical Design    Send Orders for Reprints to reprints@benthamscience.ae 6306 Current Pharmaceutical Design, 2016, 22, 6306-6312 REVIEW ARTICLE A Review of Clinical Trials of Belimumab in the Management of Systemic Lupus Erythematosus Alexis Garcia* and Juan B. De Sanctis Instituto de Inmunología, Facultad de Medicina, Universidad Central de Venezuela, FOCIS Center of Excellence, Caracas, Venezuela A R T I C L E H I S T O R Y Received: July 1, 2016 Accepted: August 29, 2016 DOI: 10.2174/13816128226661608311 03254 Abstract: There have been few changes over the last 50 years in the treatment of Systemic lupus erythematosus (SLE), using non-specific anti-inflammatory agents such as: non- steroidal anti-inflammatory drugs along with the immune cell modulating agent hydroxy- chloroquine for mild disease, and broad spectrum immunosuppressants plus anti- inflammatories such as corticosteroids, azathioprine, cyclophosphamide, or mycophenolate during flares or severe disease with organ involvement. In some patients, the response is inadequate and side effects appear from mild unpleasant up to severe toxicity. Drug metabo- lism and clearance may be severely compromised. Therefore, it is a priority to develop better treatments with fewer adverse events that can be used at different stages of disease activity. In recent years, a member of the tumor necrosis factor (TNF) family, soluble human B Lym- phocyte Stimulator protein (BLyS), also referred to as B-cell activating factor (BAFF) and TNFSF13B has been studied extensively. This protein is synthesized by myeloid cell lines, specifically interacts with B lymphocytes and increases their life-span. BlyS plays a key role in the selection, maturation and survival of B cells and it has a significant role in the pathogenesis of SLE. In this review, we analyzed the role of BLyS as a diagnostic/prognostic marker and/or therapeutic target for lupus patients, and the different clinical studies published using belimumab. Keywords: Lupus, B lymphocytes, BlyS, monoclonal antibody therapy. INTRODUCTION Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by the overproduction of autoantibodies against an array of cytoplasmic and nuclear antigens and affects multiple or- gans, such as the skin, joints, kidneys, and neuronal tissues [1]. The disease generates significant symptomatology requiring medical intervention, and it is also associated with progressive, irreversible, organ damage and consequently high morbidity and early mortality [1]. SLE affects mainly women (9:1 ratio and 10 cases per 100,000 people) and its prevalence is higher among Asians, African and admix populations as compared to Caucasians [2, 3]. The incidence has increased dramatically in the last 50 years [2, 3] and genetic factors are important in the genesis of the disease, yet non genetic factors play an important factor in the progression of the disease [3, 4]. The lack of prompt and adequate treatment increases disease progression and, in the presence of comorbidities, the subsequent increase in mortality [4]. Disease activity can be assessed either by clinical parameters such as The Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) which is the main standard scale used to evaluate disease activity or through laboratory tests: anti-double-stranded DNA (anti-dsDNA), complement determinations (C3, C4, and CH50), and erythrocyte sedimentation rate (ESR) [5]. Usually, an elevated ESR along with anti-dsDNA and low C3, C4 levels are associated with active disease, especially lupus nephritis [5]. Clinically *Address correspondence to this author at the Instituto de Inmunología, Facultad de Medicina, Universidad Central de Venezuela, Apartado 50109, Caracas 1050-A, Venezuela; Tel: +58-212-6934767; Fax: +58-212-6932815; E-mail: alexisgarcia27@gmail.com relevant lupus nephritis is associated with a 30% decrease in creatinine clearance, proteinuria, greater than 1000 mg/dL, and renal biopsy findings indicative of active nephritis. Anti-nucleo- some antibodies, that appear early in SLE, have high sensitivity and specificity for diagnosis, and titers correlate with disease activity. Anti-C1q antibodies are associated with lupus nephritis; high titers correlate with active renal disease [6]. Appropriate management of patients with flares using effective treatments to adequately suppress disproportionate immune system activation are required to bring about long-term remission of the disease [7]. Several biological agents were introduced for treatment of SLE patients in different clinical trials [8]. Nonetheless, most of the studies are conducted in small controlled-randomized studies which hamper the analysis of the therapeutic impact on the disease [8]. New data from research groups assessing inflammatory path- ways and cellular interactions generated information regarding new biological targets in patients with SLE [8, 9]. B cells are the critical cells involved in the pathogenesis of SLE and consequently, neu- tralization of autoreactive B cells, induction of tolerance, inhibition of costimulatory signals and modulation of cytokines pathways are the issues [8, 9]. Current therapeutic approaches targeting of B cells include direct depletion and inhibition of specific B cell-stimulating cytokines [8, 9]. More efforts have to be devoted to modulate im- mune response without hampering basic immune responses. GENETIC AND EPIGENETIC Large genome-wide association studies (GWAS) have used hundreds of thousands of single nucleotide polymorphism (SNP) markers in order to elaborate a predictive genotype. These studies have confirmed the importance of gene polymorphisms on immune response, inflammation, and resolution of the inflammatory re- sponse [10]. Even though genetic background involved in SLE is 1873-4286/16 $58.00+.00 © 2016 Bentham Science Publishers