Benlysta (belimumab) is an FDA-approved human monoclonal antibody used in the treatment of systemic lupus erythematosus (SLE). SLE is an autoimmune disorder in which the immune system attacks its own healthy tissues, affecting multiple organs and causing joint pain, inflammation, and sometimes a rash. Benlysta works by inhibiting B lymphocyte stimulator protein (BLyS), which causes a reduction in the B cells that attack the body’s own tissues.

Benlysta (belimumab) is also FDA-approved in the treatment of active lupus nephritis who are receiving standard therapy.

Generally, lupus patients can be treated with antimalarials (such as hydroxychloroquine), corticosteroids (such as prednisone, methylprednisolone, dexamethasone), and immunosuppressives (such as methotrexate, azathioprine, mycophenolate, or cyclophosphamide).

Benlysta (belimumab) has a place in therapy for lupus patients who are not responsive to the conventional agents outlined above and who have active disease. However, Benlysta (belimumab) is not used in patients with severe active central nervous system lupus.

Benlysta (belimumab) is available as an intravenous (IV) and subcutaneous (SC) injection and is dosed every 4 weeks (IV) or every week (SC). The IV and SC formulations should not be used simultaneously.

Table 1: Dosage Information

• Indication
• Initial dose
• Subsequent dose
• Additional Considerations

• Systemic lupus erythematosus (SLE) - IV infusion
• 10 mg/kg IV every 2 weeks for the first 3 doses
• 10 mg/kg IV every 4 weeks thereafter

• Systemic lupus erythematosus (SLE) - SC injection
• 200 mg SC once weekly ongoing
• Transition from IV to SC dosing: administer first SC dose 1 to 4 weeks after the last IV dose

• Lupus nephritis (LN) - IV infusion
• 10 mg/kg IV every 2 weeks for the first 3 doses
• 10 mg/kg IV every 4 weeks thereafter
• Patient should receive first 2 IV doses before transitioning to SC dosing

• Lupus nephritis (LN) - SC injection
• 400 mg SC once weekly for first 4 doses
• 200 mg subQ once weekly thereafter
• Transition from IV to SC dosing: administer first SC dose 1 to 2 weeks after the last IV dose

Definitions

Antimalarial

a drug class that is used to treat malaria but also is used in autoimmune diseases such as lupus and rheumatoid arthritis.

Autoantibody

is an antibody produced by one’s own immune system that attacks the body’s normal cells, rather than foreign antigens (such as viruses and bacteria).

B cells

are cells in the body that help activate an immune response.

B lymphocyte stimulator protein (BLyS)

is a molecule in the body that aids in the development of B cells.

Central nervous system lupus

is a complication that can be seen in lupus patients and can involve conditions such as seizures, cerebrovascular accidents (strokes), delirium, and nerve pain.

Corticosteroid

is a drug class that reduces inflammation and suppresses the immune system.

Human monoclonal antibody

is a protein made from human cells that is designed to bind to a specific molecule in the body and can be used to treat a variety of diseases including lupus, rheumatoid arthritis, and cancers.

Immunosuppressives

are medications that prevent the actions of the immune system, used in diseases such as lupus, rheumatoid arthritis, psoriasis, and Crohn’s disease.

JCV or John Cunningham virus

refers to a virus associated with the development of progressive multifocal leukoencephalopathy (PML), a side effect of certain immunosuppressive medications. Patients who use Benlysta should be tested for JCV before starting treatment and while on treatment to help identify if they are at a higher risk for PML.

Lupus nephritis

is inflammation of the kidney in patients with lupus.

Medical Necessity Criteria for Initial Authorization

The Plan considers Benlysta (belimumab) medically necessary when the ALL the following criteria are met for the applicable indication listed below:

For active systemic lupus erythematosus

1. The medication is being prescribed by a rheumatologist; AND
2. The member is 5 years of age or older; AND
3. The member has a diagnosis of active systemic lupus erythematosus and meets BOTH of the following conditions:
   1. Positive for autoantibodies (antinuclear antibody [ANA] and/or anti-double-stranded DNA [anti-dsDNA]); and
   2. Receiving standard therapy, which includes at least ONE of the following, alone or in combination:
      1. antimalarials (such as hydroxychloroquine); or
      2. corticosteroids (such as prednisone, methylprednisolone, dexamethasone); or
      3. immunosuppressives (such as azathioprine, methotrexate, mycophenolate); AND
4. The member does not have severe active central nervous system lupus (such as altered mental function or confusion, vision problems, or seizures); AND

5. The member is not using Benlysta in combination with ANY of the following:
   • other biologic therapies (such as Actemra, Enbrel, Humira, Stelara); or
   • intravenous cyclophosphamide; AND
6. The member must have no evidence of infection, specifically tuberculosis (TB), Hepatitis B (HBV), or Hepatitis C (HCV); AND
7. Chart documentation and supporting laboratory test results are provided for review to substantiate the above listed requirements.

If the above prior authorization criteria are met, Benlysta (belimumab) will be approved for 12 months.

For active lupus nephritis

1. The medication is being prescribed by a rheumatologist or nephrologist; AND
2. The member is 5 years of age or older; AND
3. The member has a diagnosis of active lupus nephritis and meets BOTH of the following conditions:
   1. Positive for autoantibodies (antinuclear antibody [ANA] and/or anti-double-stranded DNA [anti-dsDNA]); and
   2. Receiving standard therapy, which includes at least ONE of the following, alone or in combination:
      1. calcineurin inhibitors (such as cyclosporine, tacrolimus); or
      2. corticosteroids (such as prednisone, methylprednisolone, dexamethasone); or
      3. immunosuppressives (such as azathioprine, mycophenolate); AND
4. The member does not have severe active central nervous system lupus (such as altered mental function or confusion, vision problems, or seizures); AND
5. The member is not using Benlysta in combination with other biologic therapies (such as Actemra, Enbrel, Humira, Stelara); AND
6. The member must have no evidence of infection, specifically tuberculosis (TB), Hepatitis B (HBV), or Hepatitis C (HCV); AND
7. Chart documentation and supporting laboratory test results are provided for review to substantiate the above listed requirements.

If the above prior authorization criteria are met, Benlysta (belimumab) will be approved for 12 months.

Medical Necessity Criteria for Reauthorization

Reauthorization for 12 months will be granted if BOTH of the following are met:

1. the member still meets the applicable Initial Authorization criteria; and
2. recent chart documentation (within the last 6 months) shows ONE of the following:
   1. the member has shown a clinical improvement (e.g., sustained improvement in disease activity and reductions in disease flares) in symptoms since starting the requested medication; or
   2. the member has experienced disease stability (e.g., complete remission, low disease activity state, no new lupus disease activity compared with the previous assessment) since starting the requested medication.

Experimental or Investigational / Not Medically Necessary

Benlysta (belimumab) for any other indication is considered not medically necessary by the Plan, as it is deemed to be experimental, investigational, or unproven. Non-covered indications include, but are not limited to, the following:

• Immunoglobulin G4 Related Sclerosing Disease
• Immune Thrombocytopenia (ITP)
• Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis / Granulomatosis With Polyangiitis
• Chronic Obstructive Pulmonary Disease (COPD) / Emphysema
• Myasthenia Gravis
• Rheumatoid Arthritis
• Sjogren's Syndrome (SS)
• Cryoglobulinemia
• Vasculitis
• Relapsed Chronic Lymphocytic Leukemia
• Anti-Phospholipids Syndrome (APS)
• Graft-versus-host Disease (GVHD)
• Idiopathic CD4 Lymphocytopenia
• Neuromyelitis Optica Spectrum Disorders
• Discoid Lupus Erythematosus (DLE)