Skip to main content

Belimumab: A Review in Systemic Lupus Erythematosus

Drugs volume 78, pages 355–366 (2018)Cite this article

Abstract

Belimumab (Benlysta®) is a human immunoglobulin G1λ monoclonal antibody that inhibits the binding of soluble B lymphocyte stimulator to B cells. It is the only biological agent currently approved for the treatment of non-renal systemic lupus erythematosus (SLE). Belimumab is approved in the EU, the USA and other countries as add-on therapy in adult patients with active, autoantibody-positive SLE despite standard therapy. In phase III trials, treatment with IV or SC belimumab plus standard therapy was effective in terms of reducing overall disease activity and reducing the incidence and severity of flares, without worsening of patients’ overall condition or the development of significant disease activity in new organ systems. Sustained disease control was maintained during longer-term (up to 10 years) treatment with IV belimumab. Belimumab also demonstrated steroid-sparing effects and was associated with clinically meaningful improvements in health-related quality of life and fatigue. Belimumab was generally well tolerated in clinical trials, with low rates of immunogenicity. In view of the flexibility regarding the route of administration and the convenience of the once-weekly, self-administered, SC regimen, add-on therapy with belimumab is a useful treatment option for patients with active, autoantibody-positive SLE despite standard therapy.

This is a preview of subscription content, access via your institution.

Access options

Buy single article

Instant access to the full article PDF.

49,54 €

Price includes VAT (Finland)
Tax calculation will be finalised during checkout.

References

  1. Hui-Yuen JS, Li XQ, Askanase AD. Belimumab in systemic lupus erythematosus: a perspective review. Ther Adv Musculoskelet Dis. 2015;7(4):115–21.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  2. Garcia A, De Sanctis JB. A review of clinical trials of belimumab in the management of systemic lupus erythematosus. Curr Pharm Des. 2016;22(41):6306–12.

    CAS  Article  PubMed  Google Scholar 

  3. Furie R, Stohl W, Ginzler EM, 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(5):R109.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Sifuentes Giraldo WA, Garcia Villanueva MJ, Boteanu AL, et al. New targets in systemic lupus (part 2/2). Reumatol Clin. 2012;8(5):263–9.

    Article  PubMed  Google Scholar 

  5. European Medicines Agency. Benlysta® (belimumab): summary of product characteristics. 2017. http://www.ema.europa.eu. Accessed 18 Jan 2018.

  6. GlaxoSmithKline. Benlysta® (belimumab): US prescribing information. 2017. https://www.accessdata.fda.gov. Accessed 18 Jan 2018.

  7. Burness CB, McCormack PL. Belimumab: in systemic lupus erythematosus. Drugs. 2011;71(18):2435–44.

    CAS  Article  PubMed  Google Scholar 

  8. Baker KP, Edwards BM, Main SH, et al. Generation and characterization of LymphoStat-B, a human monoclonal antibody that antagonizes the bioactivities of B lymphocyte stimulator. Arthritis Rheum. 2003;48(11):3253–65.

    CAS  Article  PubMed  Google Scholar 

  9. Wallace DJ, Stohl W, Furie RA, 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(9):1168–78.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  10. Furie R, Petri M, Zamani O, et al. A phase III, randomized, placebo-controlled study of belimumab, a monoclonal antibody that inhibits B lymphocyte stimulator, in patients with systemic lupus erythematosus. Arthritis Rheum. 2011;63(12):3918–30.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  11. Navarra SV, Guzman RM, Gallacher AE, et al. Efficacy and safety of belimumab in patients with active systemic lupus erythematosus: a randomised, placebo-controlled, phase 3 trial. Lancet. 2011;377(9767):721–31.

    CAS  Article  PubMed  Google Scholar 

  12. Struemper H, Thapar M, Roth D. Population pharmacokinetic and pharmacodynamic analysis of belimumab administered subcutaneously in healthy volunteers and patients with systemic lupus erythematosus. Clin Pharmacokinet. 2017. https://doi.org/10.1007/s40262-017-0586-5.

    PubMed  Google Scholar 

  13. Struemper H, Chen C, Cai W. Population pharmacokinetics of belimumab following intravenous administration in patients with systemic lupus erythematosus. J Clin Pharmacol. 2013;53(7):711–20.

    Article  PubMed  Google Scholar 

  14. Yapa SW, Roth D, Gordon D, et al. Comparison of intravenous and subcutaneous exposure supporting dose selection of subcutaneous belimumab systemic lupus erythematosus phase 3 program. Lupus. 2016;25(13):1448–55.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  15. Chatham WW, Wallace DJ, Stohl W, et al. Effect of belimumab on vaccine antigen antibodies to influenza, pneumococcal, and tetanus vaccines in patients with systemic lupus erythematosus in the BLISS-76 trial. J Rheumatol. 2012;39(8):1632–40.

    CAS  Article  PubMed  Google Scholar 

  16. Chatham W, Chadha A, Fettiplace J, et al. A randomized, open-label study to investigate the effect of belimumab on pneumococcal vaccination in patients with active, autoantibody-positive systemic lupus erythematosus. Lupus. 2017;26(14):1483–90.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  17. Zhang F, Bae SC, Bass D, et al. A pivotal phase III, randomized, placebo-controlled study of belimumab in patients with systemic lupus erythematosus located in China, Japan, and South Korea [abstract no. 742 plus poster]. Arthritis Rheumatol. 2016;68(Suppl 10):988–9.

    Google Scholar 

  18. Tanaka Y, Bass D, Chu M, et al. Effects of belimumab on corticosteroid use in a pivotal phase III, randomised, placebo controlled study in subjects with systemic lupus erythematosus in North East Asia [abstract no. 106 plus poster]. Lupus Sci Med. 2017;4(1):A45–6.

    Google Scholar 

  19. Wallace DJ, Ginzler EM, Merrill JT, et al. Sustained safety and efficacy over 10 years with belimumab (BEL) plus standard systemic lupus erythematosus (SLE) therapy (SOC) in patients with SLE [abstract no. OP0232 plus oral presentation]. Ann Rheum Dis. 2017;76(Suppl. 2):150–1.

    Google Scholar 

  20. Furie RA, Wallace DJ, Aranow C, et al. 7-year safety and efficacy of belimumab in patients with systemic lupus erythematosus [abstract no. 768]. Arthritis Rheumatol. 2016;68(Suppl 10):1027–8.

    Google Scholar 

  21. Strand V, Berry P, Ramachandran S, et al. Long-term impact of belimumab on health-related quality of life and fatigue in patients with systemic lupus erythematosus: up to 7 years of treatment exposure [abstract no. 3235]. Arthritis Rheumatol. 2016;68(Suppl 10):2216–7.

    Google Scholar 

  22. van Vollenhoven RF, Petri MA, Cervera R, et al. Belimumab in the treatment of systemic lupus erythematosus: high disease activity predictors of response. Ann Rheum Dis. 2012;71(8):1343–9.

    Article  PubMed  PubMed Central  Google Scholar 

  23. Manzi S, Sanchez-Guerrero J, Merrill JT, et al. Effects of belimumab, a B lymphocyte stimulator-specific inhibitor, on disease activity across multiple organ domains in patients with systemic lupus erythematosus: combined results from two phase III trials. Ann Rheum Dis. 2012;71(11):1833–8.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  24. van Vollenhoven RF, Petri M, Wallace DJ, et al. Cumulative corticosteroid dose over fifty-two weeks in patients with systemic lupus erythematosus: pooled analyses from the phase III belimumab trials. Arthritis Rheumatol. 2016;68(9):2184–92.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Strand V, Levy RA, Cervera R, et al. Improvements in health-related quality of life with belimumab, a B-lymphocyte stimulator-specific inhibitor, in patients with autoantibody-positive systemic lupus erythematosus from the randomised controlled BLISS trials. Ann Rheum Dis. 2014;73(5):838–44.

    CAS  Article  PubMed  Google Scholar 

  26. Bruce IN, Urowitz M, van Vollenhoven R, et al. Long-term organ damage accrual and safety in patients with SLE treated with belimumab plus standard of care. Lupus. 2016;25(7):699–709.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  27. Urowitz M, Ohsfeldt RL, Wielage R, et al. A propensity score-matched study of organ damage in patients with systemic lupus erythematosus from the BLISS long-term extension trials versus the toronto lupus cohort: a post hoc longitudinal analysis [abstract no. 2923]. Arthritis Rheumatol. 2017;69(Suppl. 10):4217–8.

    Google Scholar 

  28. Collins CE, Dall’Era M, Kan H, et al. Response to belimumab among patients with systemic lupus erythematosus in clinical practice settings: 24-month results from the OBSErve study in the USA. Lupus Sci Med. 2016;3(1):e000118.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  29. Hui-Yuen JS, Reddy A, Taylor J, et al. Safety and efficacy of belimumab to treat systemic lupus erythematosus in academic clinical practices. J Rheumatol. 2015;42(12):2288–95.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  30. Stott-Miller M, Egger P, Eudy A, et al. Impact of belimumab use on flares among patients diagnosed with systemic lupus erythematosus (SLE) in a US commercially insured database: 2010-2014 [abstract no. OP0039]. Ann Rheum Dis. 2016;75(Suppl 2):68.

    Article  Google Scholar 

  31. Schwarting A, Schroeder JO, Alexander T, et al. First real-world insights into belimumab use and outcomes in routine clinical care of systemic lupus erythematosus in Germany: results from the OBSErve Germany study. Rheumatol Ther. 2016;3(2):271–90.

    Article  PubMed  PubMed Central  Google Scholar 

  32. Cortes J, Andreu JL, Calvo J, et al. Evaluation of use of belimumab in clinical practice settings (OBSERVE study) in Spain: health resource utilization and labour absenteeism [abstract no. PSY73]. Value Health. 2014;17(7):A534.

    CAS  Article  PubMed  Google Scholar 

  33. Touma Z, Sayani A, Pineau CA, et al. Belimumab use, clinical outcomes and glucocorticoid reduction in patients with systemic lupus erythematosus receiving belimumab in clinical practice settings: results from the OBSErve Canada Study. Rheumatol Int. 2017;37(6):865–73.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  34. Garcia M, Pons-Estel BA, Babini A, et al. Evaluation of use of belimumab in clinical practice settings (OBSERVE) in Argentina [abstract no. P4.14]. Clin Exp Rheumatol. 2015;33(3 Suppl 90):S31.

  35. Parodis I, Sjöwall A, Jönsen A, et al. Decreased disease activity and corticosteroid usage and improved quality of life during belimumab treatment in patients with systemic lupus erythematosus—a prospective real-life observational study [abstract no. 732]. Arthritis Rheumatol. 2015;67(Suppl 10):994.

    Google Scholar 

  36. Iaccarino L, Bettio S, Reggia R, et al. Effects of belimumab on flare rate and expected damage progression in patients with active systemic lupus erythematosus. Arthritis Care Res. 2016;69(1):115–23.

    Article  Google Scholar 

  37. Iaccarino L, Andreoli L, Bocci EB, et al. Clinical predictors of response and discontinuation of belimumab in patients with systemic lupus erythematosus in real life setting. Results of a large, multicentric, nationwide study. J Autoimmun. 2018;86:1–8.

    CAS  Article  PubMed  Google Scholar 

  38. Fanouriakis A, Adamichou C, Koutsoviti S, et al. Real-life experience with belimumab in systemic lupus erythematosus (SLE): control of disease activity and flares in a multicenter cohort [abstract no. AB0442]. Ann Rheum Dis. 2017;76(Suppl. 2):1204–5.

    Google Scholar 

  39. Scheinberg M, de Melo FF, Bueno AN, et al. Belimumab for the treatment of corticosteroid-dependent systemic lupus erythematosus: from clinical trials to real-life experience after 1 year of use in 48 Brazilian patients. Clin Rheumatol. 2016;35(7):1719–23.

    Article  PubMed  Google Scholar 

  40. Parodis I, Sjowall C, Jonsen A, et al. Smoking and pre-existing organ damage reduce the efficacy of belimumab in systemic lupus erythematosus. Autoimmun Rev. 2017;16(4):343–51.

    CAS  Article  PubMed  Google Scholar 

  41. Pascoe K, Lobosco S, Bell D, et al. Satisfaction and impact associated with the addition of belimumab to systemic lupus erythematosus (SLE) treatment: a cross-sectional survey of US rheumatologists and their patients [abstract no. 741]. Arthritis Rheumatol. 2015;67(Suppl 10):1005–7.

    Google Scholar 

  42. Stohl W, Schwarting A, Okada M, et al. Efficacy and safety of subcutaneous belimumab in systemic lupus erythematosus: a fifty-two-week randomized, double-blind, placebo-controlled study. Arthritis Rheumatol. 2017;69(5):1016–27.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  43. Doria A, Stohl W, Schwarting A, et al. Safety of subcutaneous belimumab in patients with systemic lupus erythematosus: a 6-month open-label extension study [abstract no. SAT0231]. Ann Rheum Dis. 2017;76(Suppl. 2):861.

    Google Scholar 

  44. Doria A, Pobiner B, Eastman W, et al. Subcutaneous belimumab plus standard of care demonstrated improvement in multiple organ domains versus placebo plus standard of care in patients with active systemic lupus erythematosus (SLE) [abstract no. 2590]. Arthritis Rheumatol. 2017;69(Suppl. 10):3731–3.

    Google Scholar 

  45. Van Vollenhoven RF, Thompson A, Pobiner B, et al. The effect of subcutaneous belimumab on corticosteroid use in patients with systemic lupus erythematosus (SLE): a phase 3, randomized, placebo-controlled study [abstract no. 2604]. Arthritis Rheumatol. 2017;69(Suppl. 10):3757–8.

    Google Scholar 

  46. Krishna M, Nadler SG. Immunogenicity to biotherapeutics—the role of anti-drug immune complexes. Front Immunol. 2016;7:21. https://doi.org/10.3389/fimmu.2016.00021.

    Article  PubMed  PubMed Central  Google Scholar 

  47. Guidelines for referral and management of systemic lupus erythematosus in adults. American College of Rheumatology Ad Hoc Committee on Systemic Lupus Erythematosus Guidelines. Arthritis Rheum. 1999;42(9):1785–96.

  48. Bertsias G, Ioannidis JP, Boletis J, et al. EULAR recommendations for the management of systemic lupus erythematosus. Report of a task force of the EULAR standing committee for international clinical studies including therapeutics. Ann Rheum Dis. 2008;67(2):195–205.

    CAS  Article  PubMed  Google Scholar 

  49. Kleinmann JF, Tubach F, Le Guern V, et al. International and multidisciplinary expert recommendations for the use of biologics in systemic lupus erythematosus. Autoimmun Rev. 2017;16(6):650–7.

    CAS  Article  PubMed  Google Scholar 

  50. National Institute for Health and Care Excellence. Belimumab for treating active autoantibody-positive systemic lupus erythematosus. 2016. https://www.nice.org.uk. Accessed 18 Jan 2018.

  51. American College of Rheumatology Ad Hoc Committee on Systemic Lupus Erythematosus Response Criteria. The American College of Rheumatology response criteria for systemic lupus erythematosus clinical trials. Measures of overall disease activity. Arthritis Rheum. 2004;50(11):3418–26.

    Article  Google Scholar 

  52. Dashiell-Aje E, Harding G, Pascoe K, et al. Patient evaluation of satisfaction and outcomes with an autoinjector for self-administration of subcutaneous belimumab in patients with systemic lupus erythematosus. Patient. 2018;11(1):119–29.

    Article  PubMed  Google Scholar 

  53. Lee YH, Song GG. Comparative efficacy and safety of intravenous or subcutaneous belimumab in combination with standard therapy in patients with active systemic lupus erythematosus: a Bayesian network meta-analysis of randomized controlled trials. Lupus. 2017;27(1):112–9.

    Article  PubMed  Google Scholar 

  54. Jordan N, D’Cruz DP. Belimumab for the treatment of systemic lupus erythematosus. Expert Rev Clin Immunol. 2015;11(2):195–204.

    CAS  Article  PubMed  Google Scholar 

  55. Vallejo-Aparicio LA, Diaz-Cerezo S, Parrondo J, et al. Cost-effectiveness analysis of belimumab in the treatment of adult systemic lupus erythematosus (SLE) patients with positive biomarkers in Spain [abstract no. PSY53]. Value Health. 2014;17(7):A530.

    CAS  Article  PubMed  Google Scholar 

  56. Athanasakis K, Karampli E, Ollandezos M, et al. Belimumab for the treatment of systemic lupus erythematosus (SLE) in Greece: a cost-effectiveness and cost-utility analysis [abstract no. PSY64]. Value Health. 2014;17(7):A532–3.

    CAS  Article  PubMed  Google Scholar 

  57. Pierotti F, Palla I, Treur M, et al. Assessment of the economic impact of belimumab for the treatment of systemic lupus erythematosus in the Italian setting: a cost-effectiveness analysis. PLoS One. 2015;10(10):e0140843.

    Article  PubMed  PubMed Central  Google Scholar 

  58. Carter EE, Barr SG, Clarke AE. The global burden of SLE: prevalence, health disparities and socioeconomic impact. Nat Rev Rheumatol. 2016;12(10):605–20.

    Article  PubMed  Google Scholar 

  59. US National Institutes of Health. 2017. http://www.clinicaltrials.gov. Accessed 18 Jan 2018.

Download references

Acknowledgements

During the peer review process, the manufacturer of belimumab was also offered an opportunity to review this article. Changes resulting from comments received were made on the basis of scientific and editorial merit.

Author information

Affiliations

  1. Springer, Private Bag 65901, Mairangi Bay, Auckland, 0754, New Zealand

    Hannah A. Blair & Sean T. Duggan

Authors
  1. Hannah A. Blair
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Sean T. Duggan
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Hannah A. Blair.

Ethics declarations

Funding

The preparation of this review was not supported by any external funding.

Conflict of interest

Hannah Blair and Sean Duggan are salaried employees of Adis/Springer, are responsible for the article content and declare no relevant conflicts of interest.

Additional information about this Adis Drug Review can be found at http://www.medengine.com/Redeem/DCD8F0603CADACA0.

Additional information

The manuscript was reviewed by: M. A. Khamashta, Lupus Research Unit, St Thomas’ Hospital, London, UK; R. A. Levy, Department of Rheumatology, State University of Rio de Janeiro, Brazil; Y. J. Poh, Department of Rheumatology and Immunology, Singapore General Hospital, Singapore, Singapore; C. Richez, Department of Rheumatology, Hopital Pellegrin, Bordeaux, France.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Blair, H.A., Duggan, S.T. Belimumab: A Review in Systemic Lupus Erythematosus. Drugs 78, 355–366 (2018). https://doi.org/10.1007/s40265-018-0872-z

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40265-018-0872-z