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Belimumab: Review of Use in Systemic Lupus Erythematosus

  • Eric G. Boyce
    Correspondence
    Address correspondence to: Eric G. Boyce, PharmD, Thomas J. Long School of Pharmacy and Health Sciences, University of the Pacific, 3601 Pacific Avenue, Stockton, CA 95211
    Affiliations
    Department of Pharmacy Practice, Thomas J. Long School of Pharmacy and Health Sciences, University of the Pacific, Stockton, California
    Search for articles by this author
  • Bryan E. Fusco
    Affiliations
    Department of Pharmacy Practice, Thomas J. Long School of Pharmacy and Health Sciences, University of the Pacific, Stockton, California
    Search for articles by this author

      Abstract

      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.

      Key words

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      References

        • Human Genome Sciences, Inc. and GlaxoSmithKline
        Belimumab [package insert].
        (Accessed November 7, 2011)
        • GlaxoSmithKline
        Benlysta Product Monograph.
        (Accessed November 7, 2011)
        • US Food and Drug Administration
        FDA approves Benlysta to treat lupus.
        (Accessed October 16, 2011)
        • Zacks Investment Research
        CHMP backs Benlysta.
        (Accessed October 28, 2011)
        • Health Canada
        Summary Basis of Decision (SBD) for BENLYSTA.
        (Accessed January 26, 2012)
        • Rahman A.
        • Isenberg D.A.
        Systemic lupus erythematosus: mechanism of disease.
        N Engl J Med. 2008; 358: 929-939
        • Tan E.M.
        • Cohen A.S.
        • Fries J.F.
        • et al.
        The 1982 revised criteria for the classification of systemic lupus erythematosus.
        Arthritis Rheum. 1982; 25: 1271-1277
        • Hochberg M.C.
        Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus.
        Arthritis Rheum. 1997; 40 (Letter): 1725
        • Bertsias G.K.
        • Ioannidis J.P.A.
        • Boletis J.
        • et al.
        EULAR recommendations for the management of systemic lupus erythematosus (SLE): report of a task force of the European Standing Committee for International Clinical Studies Including Therapeutics.
        Ann Rheum Dis. 2009; 68: 477-483
        • US Department of Health and Human Services, Food and Drug Administration, Center for Drug Evaluation and Research, Center for Biologics Evaluation and Research, Center for Devices and Radiological Health
        Guidance for industry: systemic lupus erythematosus—developing medical products for treatment.
        (Accessed November 7, 2011)
        • Lee S.
        • Ballow M.
        Monoclonal antibodies and fusion proteins and their complications: targeting B cells in autoimmune diseases.
        J Allergy Clin Immunol. 2010; 125: 814-820
        • Baker K.P.
        • Edwards B.M.
        • Main S.H.
        • et al.
        Generation and characterization of LymphoStat-B, a human monoclonal antibody that antagonizes the bioactivities of B lymphocyte stimulator.
        Arthritis Rheum. 2003; 48: 3253-3265
        • Petri M.
        • Stohl W.
        • Chatham W.
        • et al.
        Association of plasma B-lymphocyte stimulator (BLyS) levels and disease activity in systemic lupus erythematosus.
        Arthritis Rheum. 2008; 58: 2453-2459
        • Furie R.A.
        • Petri M.A.
        • Wallace D.J.
        • et al.
        Novel evidence-based systemic lupus erythematosus responder index.
        Arthritis Rheum. 2009; 61: 1143-1151
        • Hay E.M.
        • Bacon P.A.
        • Gordon C.
        • et al.
        The BILAG index: a reliable and valid instrument for measuring clinical disease activity in systemic lupus erythematosus.
        Q J Med. 1993; 86: 447-458
        • Petri M.
        • Kim M.Y.
        • Kalunian K.C.
        • et al.
        • OC-SELENA Trial
        Combined oral contraceptives in women with systemic lupus erythematosus.
        N Engl J Med. 2005; 353: 2550-2558
        • Isenberg D.A.
        • Allen E.
        • Farewell V.
        • et al.
        An assessment of disease flare in patients with systemic lupus erythematosus: a comparison of BILAG 2004 and the flare version of SELENA.
        Ann Rheum Dis. 2011; 70: 54-59
        • Kuhn A.
        • Ruland V.
        • Bonsmann G.
        Cutaneous lupus erythematosus: Update of therapeutic options: part I.
        J Am Acad Dermatol. 2011; 65: e179-e193
        • Kuhn A.
        • Ruland V.
        • Bonsmann G.
        Cutaneous lupus erythematosus: Update of therapeutic options: part II.
        J Am Acad Dermatol. 2011; 65: e195-e213
        • Lander S.A.
        • Wallace D.J.
        • Weisman M.H.
        Celecoxib for systemic lupus erythematosus: case series and literature review of the use of NSAIDs in SLE.
        Lupus. 2002; 11: 340-347
        • Horizon A.A.
        • Wallace D.J.
        Risk: benefit ratio of nonsteroidal anti-inflammatory drugs in systemic lupus erythematosus.
        Expert Opin Drug Saf. 2004; 3: 273-278
        • Man B.L.
        • Mok C.C.
        Serositis related to systemic lupus erythematosus: prevalence and outcome.
        Lupus. 2005; 14: 822-826
        • Pauzner R.
        • Dulitzki M.
        • Langevitz P.
        • et al.
        Low molecular weight heparin and warfarin in the treatment of patients with antiphospholipid syndrome during pregnancy.
        Thromb Haemost. 2001; 86: 1379-1384
        • Crowther M.A.
        • Ginsberg J.S.
        • Julian J.
        • et al.
        A comparison of two intensities of warfarin for the prevention of recurrent thrombosis in patients with the antiphospholipid antibody syndrome.
        N Engl J Med. 2003; 349: 1133-1138
        • Barile-Fabris L.
        • Ariza-Andraca R.
        • Olguin-Ortega L.
        • et al.
        Controlled clinical trial of IV cyclophosphamide versus IV methylprednisolone in severe neurological manifestations in systemic lupus erythematosus.
        Ann Rheum Dis. 2005; 64: 620-625
        • Tokunga M.
        • Saito K.
        • Kawabata D.
        • et al.
        Efficacy of rituximab (anti-CD20) for refractory systemic lupus erythematosus involving the central nervous system.
        Ann Rheum Dis. 2007; 66: 470-475
        • Ginzler E.M.
        • Dooley M.A.
        • Aranow C.
        • et al.
        Mycophenolate mofetil or intravenous cyclophosphamide for lupus nephritis.
        N Engl J Med. 2005; 353: 2219-2228
        • Gunnarsson I.
        • Sundelin B.
        • Jónsdóttir T.
        • et al.
        Histopathologic and clinical outcome of rituximab treatment in patients with cyclophosphamide-resistant proliferative lupus nephritis.
        Arthr Rheum. 2007; 56: 1263-1272
        • Halpern W.G.
        • Lappin P.
        • Zanardi T.
        • et al.
        Chronic administration of belimumab, a BLyS antagonist, decreases tissue and peripheral blood B-lymphocyte populations in cynomolgus monkeys: pharmacokinetic, pharmacodynamic, and toxicologic effects.
        Toxicol Sci. 2006; 91: 586-599
        • Jacobi A.M.
        • Huang W.
        • Wang T.
        The effect of prolonged treatment with belimumab on B cells in human SLE.
        Arthritis Rheum. 2010; 62: 201-210
        • Furie R.
        • Stohl W.
        • Ginzler E.M.
        • et al.
        Biologic activity and safety of belimumab, a neutralizing anti-B-lymphocyte stimulator (BLyS) monoclonal antibody: a phase I trial in patients with systemic lupus erythematosus.
        Arthritis Res Ther. 2008; 10: R109
        • Auyeung-Kima D.J.
        • Devalarajab M.N.
        • Migoneb T.S.
        • et al.
        Developmental and peri-postnatal study in cynomolgus monkeys with belimumab, a monoclonal antibody directed against B-lymphocyte stimulator.
        Reproductive Toxicol. 2009; 28: 443-455
        • Wallace D.J.
        • Stohl W.
        • Furie R.A.
        • et al.
        A phase II, randomized, double-blind, placebo-controlled, dose-ranging study of belimumab in patients with active systemic lupus erythematosus.
        Arthritis Rheum. 2009; 61: 1168-1178
        • Navarra S.V.
        • Guzmán R.M.
        • Gallacher A.E.
        • et al.
        Efficacy and safety of belimumab in patients with active systemic lupus erythematosus: a randomised, placebo-controlled, phase 3 trial.
        Lancet. 2011; 377: 721-731
        • Furie R.
        • Petri M.
        • Zamani O.
        • et al.
        A phase 3, randomized, placebo-controlled study of belimumab, a monoclonal antibody that inhibits BLyS, in patients with systemic lupus erythematosus.
        Arthritis Rheum. 2011; 63: 3918-3930
        • Food and Drug Administration
        Code of Federal Regulations Title 21, Part 201, Subpart B, Sec. 201.57, (c) (9) (i) 8.1 Pregnancy.
        (Accessed November 7, 2011)
        • American College of Rheumatology
        Hotline: belimumab for systemic lupus erythematosus.
        (Accessed November 2, 2011)
        • Slawsky K.A.
        • Fernandes A.W.
        • Fusfeld L.
        • et al.
        A structured literature review of the direct costs of adult systemic lupus erythematosus in the US.
        Arthritis Care Res. 2011; 63: 1224-1232
        • Zhu T.Y.
        • Tam L.S.
        • Li E.K.
        Cost-of-illness studies in systemic lupus erythematosus: a systematic review.
        Arthritis Care Res. 2011; 63: 751-760