Background

Benlysta is a recombinant, fully human, IgG1λ monoclonal antibody that is indicated for the treatment of active SLE and active LN. It works by binding to and inhibiting the biological activity of soluble B lymphocyte stimulator (BLyS) protein, a member of the tumor necrosis factor (TNF) ligand family. BLyS plays a role in B cell selection and survival and is expressed by a variety of cell types, including neutrophils, monocytes, macrophages, dendritic cells, and T cells. There are 3 receptors for BLyS. BLyS receptor 3 (BR3) is the only BLyS receptor found on newly formed and mature primary B cells, and BLyS is its only ligand. Blockade by Benlysta is expected to affect these cells more than memory B cells and plasma cells, which have other ligand activators. Benlysta is available in two forms: IV and subcutaneous. The IV form is dosed at 10 mg/kg at 2 week intervals for the first 3 doses and at 4 week intervals thereafter. The subcutaneous version requires a loading dose of 400 mg weekly for the first 4 doses when treating LN but is given as 200 mg once weekly for SLE and LN maintenance. Subcutaneous dosing of Benlysta has not been evaluated and is not approved for patients younger than 18 years of age.

Systemic Lupus Erythematosus (SLE)

SLE is a chronic inflammatory disease of unknown cause that can affect the mucocutaneous, gastrointestinal, hematologic, musculoskeletal, neurologic, psychiatric, pulmonary, renal and reproductive systems. Immunologic abnormalities are a prominent feature of the disease. For example, autoantibodies against dsDNA (i.e., anti-dsDNA) and Smith nuclear antigen (i.e. anti-Sm) are highly specific for SLE. Increases in anti-dsDNA titers, erythrocyte sedimentation rate (ESR), and serum C-reactive protein (CRP), and a decrease in serum complement levels, often precede active SLE. Treatment options for SLE include prednisone, hydroxychloroquine, NSAIDs and immunosuppressive agents, such as cyclophosphamide, methotrexate, azathioprine and mycophenolate.  

Lupus Nephritis (LN)

LN is renal complication of SLE that is characterized by an inflammatory response to immune complexes in the kidney. It occurs in approximately 40% of patients with SLE and it may be diagnosed prior to SLE. Patients with SLE should be screened regularly for LN via urinalysis and assessment of kidney function. When these screenings are abnormal, kidney biopsy should be considered to confirm the diagnosis and determine the classification of disease. Treatment of LN may include corticosteroids, cyclophosphamide, mycophenolate mofetil and hydroxychloroquine. Response to treatment is often slow, and relapses are reported in nearly 50% of patients. LN may worsen over time, with 10% – 30% of patients developing kidney failure requiring dialysis or kidney transplantation. 

Policy

The use of Benlysta is MEDICALLY NECESSARY for systemic lupus erythematosus when the following criteria has been met:

• Diagnosis of active systemic lupus erythematosus (SLE)
• Autoantibody positive (i.e., anti-nuclear antibody [ANA] titer greater than or equal to 1:80 or anti-dsDNA level greater than or equal to 30 IU/mL)
• One of the following:
  1. For Benlysta IV, patient is 5 years of age or older
  2. For Benlysta SC, patient is at least 5 years of age and weighs at least 15 kg
• Trial and failure, contraindication, or intolerance to two standard of care treatments for active SLE (e.g., antimalarials [e.g., Plaquenil (hydroxychloroquine)], corticosteroids [e.g., prednisone], or immunosuppressants [e.g., methotrexate, Imuran (azathioprine)])
• Currently receiving at least one standard of care treatment for active SLE (e.g., antimalarials [e.g., Plaquenil (hydroxychloroquine)], corticosteroids [e.g., prednisone], or immunosuppressants [e.g., methotrexate, Imuran (azathioprine)])
• Prescribed by or in consultation with a rheumatologist

The use of Benlysta is MEDICALLY NECESSARY for active lupus nephritis when the following criteria has been met:

• Diagnosis of active lupus nephritis
• One of the following:
  • For Benlysta IV, patient is 5 years of age or older
  • For Benlysta SC, patient is 18 years of age or older
• Currently receiving standard of care treatment for active lupus nephritis (e.g., corticosteroids [e.g., prednisone] with mycophenolate or cyclophosphamide)
• Prescribed by or in consultation with one of the following:
  • Nephrologist
  • Rheumatologist

The use of Benlysta is MEDICALLY NECESSARY for reauthorization when the following criteria has been met:

Documentation of positive clinical response to therapy (e.g., decrease or stabilization of symptoms, improvement in functional impairment, decrease of corticosteroid dose, decrease in pain medications)

References

1. Benlysta [package insert]. GlaxoSmithKline. Research Triangle Park, North Carolina. Updated May 2024.
2. UpToDate. Systemic Lupus Erythematosus.  
3. Inflammatory Conditions- Benlysta SC Prior Authorization Policy. Express Scripts. Updated July 2018.
4. Lupkynis Drug Evaluation. Express Scripts. Updated February 2021.  
5. Data on file.  Benlysta for intravenous infusion; BLA125370.  Briefing document for Arthritis Advisory Committee.  November 16, 2010.  Accessed March 18, 2011.  Available at:  http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/ Drugs/ArthritisDrugsAdvisoryCommittee/UCM233581.pdf .
6. Navarra SV, Guzmán RM, Gallacher AE, et al.  Efficacy and safety of belimumab in patients with active systemic lupus erythematosus: a randomised, placebocontrolled, phase 3 trial.  Lancet. 2011 Feb 26;377(9767):721-731.
7. van Vollenhoven RF, Zaamo P. Wallace DJ, et al.  Belimumab, a BLyS-specific inhibitor, reduces disease activity and severe flares in seropositive SLE patients:  BLISS-76 study.  Ann Rheum Dis.  2010;69(Suppl3):47.
8. Thanou-Stavraki A, Sawalha AH.  An update on belimumab for the treatment of lupus.  Biologics. 2011;5:33-43.
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):1168-1178.  
10. Chatham W, Weinstein A, Petri M, et al.  Five-year safety and efficacy experience with belimumab, a BLyS-specific inhibitor, in patients with systemic lupus erythematosus (SLE).  Ann Rheum Dis.  2010;69(Suppl3):147.
11. Ospedaliera A, della Misericordia SM.  University of Udine.  Efficacy and Safety of Belimumab in Primary Sjögren's Syndrome.  In: ClinicalTrials.gov [Internet].  Bethesda (MD):  National Library of Medicine (US).  2000- [cited 2011 Mar 15].  Available from:    http://clinicaltrials.gov/ct2/show/NCT01008982?term=belimumab&rank=8  Identifier:  NCT01008982.
12. Human Genome Sciences.  Cancer Trials Australia.  A study of belimumab in treating symptomatic Waldenstroms macroglobulinaemia.  In: ClinicalTrials.gov [Internet].  Bethesda (MD):  National Library of Medicine (US).  2000- [cited 2011 Mar 15].  Available from:    http://clinicaltrials.gov/ct2/show/NCT01142011?term=belimumab&rank=2  Identifier:  NCT01142011.
13. Human Genome Sciences.  University of Pennsylvania.  Desensitization With Belimumab in Sensitized Patients Awaiting Kidney Transplant.  In: ClinicalTrials.gov [Internet].  Bethesda (MD):  National Library of Medicine (US).  2000- [cited 2011 Mar 15].  Available from:    http://clinicaltrials.gov/ct2/show/NCT01025193?term=belimumab&rank=1  Identifier:  NCT01025193.
14. Wiglesworth AK, Ennis KM, Kockler DR.  Belimumab: a BLyS-specific inhibitor for systemic lupus erythematosus.  Ann Pharmacother. 2010;44(12):1955-1961.  
15. Lupus data/statistics.  US Department of Health & Human Services Web site.  Updated July 8, 2008.  Accessed November 19, 2010.  Available at:  http://minorityhealth.hhs.gov/templates/browse.aspx?lvl=3&lvlid=282.
16. About Lupus:  no two cases are alike.  Lupus Research Institute Web site.  Accessed March 18, 2011.  Available at:  http://www.lupusresearchinstitute.org/lupus.
17. 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.
18. Bertsias GK, Ioannidis JP, Aringer M, et al.  EULAR recommendations for the management of systemic lupus erythematosus with neuropsychiatric manifestations: report of a task force of the EULAR standing committee for clinical affairs.  Ann Rheum Dis. 2010;69(12):2074-2082.
19. FDA approves Benlysta to treat lupus. [press release]  US Food and Drug Administration Web site.  March 9, 2011.  Accessed March 9, 2011.  http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm246489.htm. 

Coding Section

Procedure and diagnosis codes on Medical Policy documents are included only as a general reference tool for each policy. They may not be all-inclusive.

This medical policy was developed through consideration of peer-reviewed medical literature generally recognized by the relevant medical community, U.S. FDA approval status, nationally accepted standards of medical practice and accepted standards of medical practice in this community, and other nonaffiliated technology evaluation centers, reference to federal regulations, other plan medical policies, and accredited national guidelines.

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