Belimumab (Benlysta® )

• Belimumab (Benlysta® ) intravenous infusion and subcutaneous injection for administration by a healthcare professional 

• For patients 5 years of age and older (intravenous, subcutaneous) with active systemic lupus erythematosus who are receiving standard therapy
• For adults (subcutaneous) and pediatric patients 5 years of age and older (intravenous) with active lupus nephritis who are receiving standard therapy
• Limitations of use: Efficacy has not been evaluated for severe active central nervous system lupus

The restricted product(s) may be considered medically necessary when the following criteria are met:

Initial Criteria for Approval:

1. The patient has a clinical diagnosis of systemic lupus erythematosus (SLE) according to American College of Rheumatology classification criteria [medical record documentation required]; AND
   1. All of the following: 
      1. The patient is autoantibody positive with ONE of the following [medical record documentation required]: 
         1. ANA (anti-nuclear antibody) above the laboratory reference range; OR 
         2. Anti-dsDNA (double stranded DNA antibody) above the laboratory reference range, or greater than two-fold the reference range if tested by ELISA; AND
      2. SLE is active with a score of 6 or greater (as documented by a SELENA-SLEDAI or as scored by a comparable standardized rating scale that reliably measures SLE disease activity) while on treatment with standard therapy (e.g., corticosteroids, antimalarials [hydroxychloroquine, chloroquine], non-steroidal anti-inflammatory drugs [NSAIDs], non-biologic immunosuppressants [azathioprine, methotrexate, cyclosporine, oral cyclophosphamide]) alone or as combination therapy [medical record documentation required]; AND 
      3. ONE of the following:
         1. The patient is 5 to less than 10 years of age; OR
         2. The patient is 10 years of age or older; AND
            1. ONE of the following:
               1. The patient has a physical or cognitive limitation that makes the utilization of a self-administered formulation unsafe or otherwise not feasible, as demonstrated by BOTH of the following [medical record documentation required]:
                  1. Inability to self-administer the medication; AND
                  2. Lack of caregiver or support system for assistance with administration of self-administered products; OR
               2. The prescriber has submitted written clinical rationale to support the use of the provider-administered formulation over a self-administered formulation [medical record documentation required]; OR 
   2. The patient has biopsy-proven lupus nephritis Class III, IV, and/or V [medical record documentation required]; AND
      1. The patient has active renal disease requiring standard therapy of corticosteroids with mycophenolate for induction and maintenance or cyclophosphamide for induction followed by azathioprine for maintenance [medical record documentation required]; AND
      2. ONE of the following: 
         1. The patient is 5 to less than 18 years of age; OR 
         2. The patient is 18 years of age or older; AND 
            1. ONE of the following:
               1. The patient has a physical or cognitive limitation that makes the utilization of a self-administered formulation unsafe or otherwise not feasible, as demonstrated by BOTH of the following [medical record documentation required]:
                  1. Inability to self-administer the medication; AND
                  2. Lack of caregiver or support system for assistance with administration of self-administered products; OR
               2. The patient has a diagnosis of lupus nephritis and has NOT yet received 2 intravenous doses in the healthcare setting [medical record documentation required]; OR
               3. The prescriber has submitted written clinical rationale to support the use of the provider-administered formulation over a self-administered formulation [medical record documentation required]; AND
2. The patient will NOT be using belimumab (Benlysta® ) in combination with another biologic immunomodulator agent; AND
3. The requested quantity does NOT exceed the maximum units allowed for the duration of approval (see table below); AND
4. For requests for injection or infusion administration of the requested medication in an inpatient or outpatient hospital setting, Site of Care Criteria applies (outlined below)*

Duration of Approval: 365 days (1 year)

Continuation Criteria for Approval: 

1. The patient was approved through Blue Cross NC initial criteria for approval; OR
2. The patient would have met initial criteria for approval at the time they started therapy; AND
3. The patient has a diagnosis of active systemic lupus erythematosus (SLE) [medical record documentation required]; AND
4. The patient has experienced a reduction > 4 points in SELENA-SLEDAI score from baseline (or similar improvement from baseline as scored by a comparable standardized rating scale that reliably measures SLE disease activity) following treatment with belimumab (Benlysta® ) indicating a therapeutic response [medical record documentation required]; AND
5. For patients with a diagnosis of active lupus nephritis:
   1. The patient has a urine protein: creatinine ratio (uPCR) ≤ 0.7 g/g [medical record documentation required]; AND 
   2. The patient has an eGFR ≥ 60 mL/min/1.73m2 [medical record documentation required]; OR 
   3. The patient’s eGFR has not decreased > 20% from baseline [medical record documentation required]; AND
6. The patient will NOT be using belimumab (Benlysta® ) in combination with another biologic immunomodulator agent; AND
7. ONE of the following:
   1. The patient has a diagnosis of active systemic lupus erythematosus (SLE); AND
      1. The patient is 5 to less than 10 years of age; OR
      2. The patient is 10 years of age or older; AND
         1. ONE of the following:
            1. The patient has a physical or cognitive limitation that makes the utilization of a self-administered formulation unsafe or otherwise not feasible, as demonstrated by BOTH of the following [medical record documentation required]: 
               1. Inability to self-administer the medication; AND 
               2. Lack of caregiver or support system for assistance with administration of self-administered products; OR
            2. The prescriber has submitted written clinical rationale to support the use of the provider-administered formulation over a self-administered formulation [medical record documentation required]; OR
   2. The patient has a diagnosis of active lupus nephritis; AND 
      1. The patient is 5 to less than 18 years of age; OR
      2. The patient is 18 years of age or older; AND
         1. ONE of the following:
            1. The patient has a physical or cognitive limitation that makes the utilization of a self-administered formulation unsafe or otherwise not feasible, as demonstrated by BOTH of the following [medical record documentation required]:
               1. Inability to self-administer the medication; AND 
               2. Lack of caregiver or support system for assistance with administration of self-administered products; OR
            2. The patient has a diagnosis of lupus nephritis and has NOT yet received 2 intravenous doses in the healthcare setting [medical record documentation required]; OR 
            3. The prescriber has submitted written clinical rationale to support the use of the provider-administered formulation over a self-administered formulation [medical record documentation required]; AND
8. The requested quantity does NOT exceed the maximum units allowed for the duration of approval (see table below); AND
9. For requests for injection or infusion administration of the requested medication in an inpatient or outpatient hospital setting, Site of Care Criteria applies (outlined below)*

Duration of Approval: 365 days (1 year)

1. For requests for injection or infusion administration in an inpatient setting, the injection or infusion may be given if the above medical necessity criteria are met AND the inpatient admission is NOT for the sole purpose of administering the injection or infusion; OR
2. For requests for injection or infusion administration in an outpatient hospital setting, the injection or infusion may be given if the above medical necessity criteria are met AND ONE of the following must be met: 
   1. History of mild adverse events that have not been successfully managed through mild pre-medication (e.g., diphenhydramine, acetaminophen, steroids, fluids, etc.); OR
   2. Inability to physically and cognitively adhere to the treatment schedule and regimen complexity; OR 
   3. New to therapy, defined as initial injection or infusion OR less than 3 months since initial injection or infusion; OR 
   4. Re-initiation of therapy, defined as ONE of the following:
      1. First injection or infusion after 6 months of no injections or infusions for drugs with an approved dosing interval less than 6 months duration; OR
      2. First injection or infusion after at least a 1-month gap in therapy outside of the approved dosing interval for drugs requiring every 6 months dosing duration; OR 
   5. Requirement of a change in the requested restricted product formulation; AND
3. If the Site of Care Medical Necessity Criteria in #1 or #2 above are not met, the injection or infusion will be administered in a home-based infusion or physician office setting with or without supervision by a certified healthcare professional.

All information referenced is from FDA package insert unless otherwise noted below.

1. Mikdashi J, Nived O. Measuring disease activity in adults with systemic lupus erythematosus: the challenges of administrative burden and responsiveness to patient concerns in clinical research. Arthritis Res Ther. 2015;17(1):183. 
2. Aringer M, Costenbader K, Daikh D, et al. 2019 European League Against Rheumatism/American College of Rheumatology classification criteria for systemic lupus erythematosus. Arthritis Rheumatol. 2019;71(9):1400-1412. 

Criteria and treatment protocols are reviewed annually by the Blue Cross NC P&T Committee, regardless of change. This policy is reviewed in Q2 annually.

August 2024: Criteria change: For active SLE indication, expanded age to 5 years and older for the subcutaneous formulation, according to updated FDA labeling. Added requirement for use of a self-administered formulation in patients 10 to less than 18 years of age with activeSLE unless certain criteria are met. Separated criteria formatting for use of the self-administered product according to age and indication, and adjusted formatting throughout policy for clarity.

July 2023: Criteria change: Updated SELENA-SLEDAI scoring requirement for SLE disease activity to 6 or greater. Updated requirement for use of the self-administered product to allow for prescriber submission of adequate written clinical rationale to support the use of the provider-administered formulation over a self-administered formulation. Updated maximum units according to coding unit definition for clarity.

August 2022: Criteria change: Expanded lupus nephritis indication criteria and dosing table to age 5 years or older.

April 2022: Criteria change: Added requirement for use of the self-administered product in patients 18 years of age or older unless certain criteria are met. Policy notification given 2/2/2022 for effective date 4/4/2022.

February 2022: Criteria update: SLE activity may be scored by a comparable standardized rating scale that reliably measures SLE disease activity.

October 2021: Criteria change: Added Site of Care medical necessity criteria. Policy notification given 8/2/2021 for effective date 10/1/2021.

July 2021: Criteria change: Medical record documentation required for all indications.

April 2021: Criteria change: Removed criteria point regarding continuing standard therapy, removed requirement of no evidence of renal disease and/or central nervous system disease, added continuation criteria, added maximum units, medical policy formatting change. Policy notification given 2/26/2021 for effective date 4/28/2021.

Further historical criteria changes and updates available upon request from Medical Policy and/or Corporate Pharmacy.