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MECHANISM OF ACTION

  • TRANSCRIPT

    NARRATOR:

    Systemic lupus erythematosus, or SLE, is the most common form of lupus.

    REFERENCE: 1. Maidhof W, Hilas O. Lupus: An overview of the disease and management options. Pharm Ther. 2012;37(4):240.

    NARRATOR:

    Patients suffer from a range of debilitating effects of this autoimmune disease . . . each and every day.

    REFERENCES: 1. Anders HJ, Saxena R, Zhao MH, et al. Lupus nephritis. Nat Rev Dis Primers. 2020;6(1):1-25. 2. Cancro MP, D’Cruz DP, Khamashta MA. The role of B lymphocyte stimulator (BLyS) in systemic lupus erythematosus. J Clin Investig. 2009;119(5):1066-1073. 3. Maidhof W, Hilas O. Lupus: An overview of the disease and management options. Pharm Ther. 2012;37(4):240.

    NARRATOR:

    SLE may manifest in 1 or multiple body systems, . . . such as the skin, . . . cardiovascular, pulmonary, . . . musculoskeletal, and renal systems, to name a few. Permanent organ damage can occur if SLE is not treated appropriately, which can have serious consequences for patients.

    ON-SCREEN TEXT:

    Skin
    Cardiovascular
    Pulmonary
    Musculoskeletal
    Renal

    REFERENCES: 1. American College of Rheumatology Ad Hoc Committee on Systemic Lupus Erythematosus Guidelines. Guidelines for referral and management of systemic lupus erythematosus in adults. Arthritis Rheum. 1999;42(9):1785-1796. 2. Anders HJ, Saxena R, Zhao MH, et al. Lupus nephritis. Nat Rev Dis Primers.
    2020;6(1):1-25. 3. Cancro MP, D’Cruz DP, Khamashta MA. The role of B lymphocyte stimulator (BLyS) in systemic lupus erythematosus. J Clin Investig. 2009;119(5):1066-1073. 4. Heinlen LD, McClain MT, Merrill J, et al. Clinical criteria for systemic lupus erythematosus precede diagnosis, and associated autoantibodies are present before clinical symptoms. Arthritis Rheum. 2007;56(7):2344-2351. 5. Lopez R, Davidson JE, Beeby MD, et al. Lupus disease activity and the risk of subsequent organ damage and mortality in a large lupus cohort. Rheumatol. 2012;51(3):491-498.

    NARRATOR:

    Inside the body, . . . B cells produce antibodies to help fight off infection. In SLE, autoreactive B cells produce autoantibodies that attack and destroy healthy tissues and organs, causing widespread inflammation.

    ON-SCREEN TEXT:

    Pathogen
    Antibodies
    B cell
    Inflammation
    Autoantibodies
    Autoreactive B Cell

    REFERENCES: 1. Cancro MP, D’Cruz DP, Khamashta MA. The role of B lymphocyte stimulator (BLyS) in systemic lupus erythematosus. J Clin Investig. 2009;119(5):1066-1073. 2. Maidhof W, Hilas O. Lupus: An overview of the disease and management options. Pharm Ther. 2012;37(4):240. 3. Marieb EN, Hoehn K, eds. Human Anatomy & Physiology. 11th ed. Pearson Education, Inc; 2019. 4. Mok CC, Lau CS. Pathogenesis of systemic lupus erythematosus. J Clin Pathol. 2003;56(7):481-490. 5. Murphy K, Weaver C. Janeway's Immunobiology. 9th ed. Garland Science; 2008.

    NARRATOR:

    In SLE with lupus nephritis, the immune system attacks and damages nephrons. Let’s take a closer look at how this happens.

    ON-SCREEN TEXT:

    Nephrons

    REFERENCE: 1. Anders HJ, Saxena R, Zhao MH, et al. Lupus nephritis. Nat Rev Dis Primers. 2020;6(1):1-25.

    NARRATOR:

    In the blood, autoantibodies bind to anti-dsDNA and form immune complexes. One mechanism of tissue damage in lupus nephritis is the formation of immune complexes that accumulate and deposit in the filtration membrane formed by podocytes in the glomeruli, which impairs kidney function. The resulting inflammation leads to a buildup of waste in the blood and protein excreted in the urine (or proteinuria), which is a defining feature of lupus nephritis in SLE. This may ultimately lead to end-stage kidney disease that requires dialysis or kidney transplant. Low levels of complement proteins in lupus nephritis make it difficult to clear immune complex deposits.

    ON-SCREEN TEXT:

    Autoantibodies
    Plasma cells
    Immune complexes
    Podocytes
    Immune complex deposit
    Damage
    Complement

    REFERENCES: 1. Almaani S, Meara A, Rovin BH. Update on lupus nephritis. Clin J Am Soc Nephrol. 2017;12(5):825-835. 2. Anders HJ, Saxena R, Zhao MH, et al. Lupus nephritis. Nat Rev Dis Primers. 2020;6(1):1-25. 3. Crow MK. Etiology and pathogenesis of systemic lupus erythematosus. Kelley and Firestein's Textbook of Rheumatology. Elsevier; 2017;1329-1344. 4. Davidson A, Berthier C, Kretzler M. Pathogenetic mechanisms in lupus nephritis. In: Dubois' Lupus Erythematosus and Related Syndromes. WB Saunders; 2013: 237-255. 5. Lech M, Anders HJ. The pathogenesis of lupus nephritis. J Am Soc Nephrol. 2013;24(9):1357-1366. 6. Marieb EN, Hoehn K, eds. Human Anatomy & Physiology. 11th ed. Pearson Education, Inc; 2019. 7. Song K, Liu L, Zhang X, Chen X. An update on genetic susceptibility in lupus nephritis. Clin Immunol. 2020;210:108272. 8. Toong C, Adelstein S, Phan TG. Clearing the complexity: immune complexes and their treatment in lupus nephritis. Int J Nephrol Renovasc Dis. 2011;4:17.

    NARRATOR:

    In treating SLE, with or without lupus nephritis, steroids can help control symptoms, but long-term use may also contribute to further organ damage. As a result, guideline and treatment recommendations suggest limiting their use or minimizing their dosage, leaving patients with few treatment options.

    ON-SCREEN TEXT:

    Continued damage

    REFERENCES: 1. American College of Rheumatology Ad Hoc Committee on Systemic Lupus Erythematosus Guidelines. Guidelines for referral and management of systemic lupus erythematosus in adults. Arthritis Rheum. 1999;42(9):1785-1796. 2. Anders HJ, Saxena R, Zhao MH, et al. Lupus nephritis. Nat Rev Dis Primers.
    2020;6(1):1-25. 3. Fanouriakis A, Kostopoulou M, Alunno A, et al. 2019 update of the EULAR recommendations for the management of systemic lupus erythematosus. Ann Rheum Dis. 2019;78(6):736-745.

    NARRATOR:

    BENLYSTA (belimumab) is designed for lupus. BENLYSTA is the only biologic with a mechanism of action that selectively targets the B-lymphocyte stimulator protein, or BLyS, a known underlying cause of SLE, with or without lupus nephritis.

    ON-SCREEN TEXT:

    BENLYSTA (belimumab)
    BLyS

    REFERENCES: 1. BENLYSTA [package insert]. Research Triangle Park, NC: GSK; 2021. 2. Neusser MA, Lindenmeyer MT, Edenhofer I, et al. Intrarenal production of
    B-cell survival factors in human lupus nephritis. Mod Pathol. 2011;24(1):98-107. 3. Stohl W, Hilbert DM. The discovery and development of belimumab: the
    anti-BLyS–lupus connection. Nat Biotechnol. 2012;30(1):69-77. 4. Suso JP, Posso-Osorio I, Jiménez CA, et al. Profile of BAFF and its receptors’ expression in lupus nephritis is associated with pathological classes. Lupus. 2018;27(5):708-715.

    NARRATOR:

    BENLYSTA selectively blocks the binding of soluble BLyS to its receptor on B cells.

    ON-SCREEN TEXT:

    B cell
    B-cell membrane
    BAFF-R
    BAFF-R: B-cell activating factor receptor

    REFERENCES: 1. BENLYSTA [package insert]. Research Triangle Park, NC: GSK; 2021. 2. Kim HM, Yu KS, Lee ME, et al. Crystal structure of the BAFF–BAFF-R complex and its implications for receptor activation. Nat Struct Mol Biol. 2003;10(5):342-348. 3. Shin W, Lee HT, Lim H, et al. BAFF-neutralizing interaction of belimumab related to its therapeutic efficacy for treating systemic lupus erythematosus. Nat Comm. 2018;9(1):1-11.

    NARRATOR:

    Although it does not bind to B cells directly, BENLYSTA inhibits the survival of autoreactive B cells and reduces the differentiation of B cells into immunoglobulin-producing plasma cells. The clinical relevance of these effects on B cells has not been established.

    ON-SCREEN TEXT:

    The clinical relevance of these effects on B cells has not been established.
    B cell
    Plasma cell

    REFERENCE: 1. BENLYSTA [package insert]. Research Triangle Park, NC: GSK; 2021.

    NARRATOR:

    In patients with SLE, treatment with BENLYSTA resulted in a 41% reduction in anti-double-stranded DNA antibody levels . . . over 52 weeks. Reductions in IgG and the SLE B-cell subset, and increases in complement proteins C3 and C4 were also observed at Week 52.

    ON-SCREEN TEXT:

    41% reduction in anti-dsDNA antibodies over 52 weeks
    The clinical relevance of these results has not been fully established.
    Reductions in: IgG, CD19+/CD20+, naïve B cells, activated B cells, B-cell subset
    Increase in complement (C3, C4)
    At Week 52

    REFERENCES: 1. BENLYSTA [package insert]. Research Triangle Park, NC: GSK; 2021. 2. Stohl W, Hiepe F, Latinis KM, et al. Belimumab reduces autoantibodies, normalizes low complement levels, and reduces select B cell populations in patients with systemic lupus erythematosus. Arthritis Rheum. 2012;64(7):2328-2337.

    NARRATOR:

    In patients with lupus nephritis, treatment with BENLYSTA led to a decrease in serum IgG as early as Week 4, and, subsequently, there was an increase in serum IgG levels, which was associated with decreased proteinuria. Reductions in autoantibodies, total circulating B cells, and B-cell subsets and increases in complement proteins were consistent with what was observed in SLE trials.

    ON-SCREEN TEXT:

    Reductions in autoantibodies
    Reductions in B cells
    Increase in complement
    The clinical relevance of these results has not been fully established.

    REFERENCE: 1. BENLYSTA [package insert]. Research Triangle Park, NC: GSK; 2021.

    NARRATOR:

    BENLYSTA. An approved treatment option for patients with SLE or lupus nephritis.

    ON-SCREEN TEXT:

    Benlysta (belimumab) Intravenous Use 120 mg/vial Subcutaneous Use 200 mg/mL
    ©2021 GSK or licensor.
    BELVID210047 February 2022
    Produced in USA.
    Trademarks owned by or licensed to the GSK group of companies.

    REFERENCE: 1. BENLYSTA [package insert]. Research Triangle Park, NC: GSK; 2021.

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