Systemic Lupus Erythematosus (SLE) & Lupus Nephritis (LN)

POLICY NUMBER

L.5.01.507

Benlysta (belimumab)

Lupkynis (voclosporin)

Saphnelo (anifrolumab-fnia)

Please perform a formulary drug search on your patient’s member ID to ensure the prescription drug is covered under their benefit plan. The medication(s) in this medical policy may not be covered under a specific member’s benefit plan.

DESCRIPTION

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease of unknown origin that can affect virtually any organ of the body. Patients present with variable clinical features ranging from mild joint and skin involvement to life-threatening renal, hematologic, or central nervous system involvement.

Most patients with SLE will have clinical evidence of kidney disease at some point in the course of their disease. Lupus nephritis (LN) typically develops early in the disease course. Diagnosis of LN is ideally confirmed by a kidney biopsy. The International Society of Nephrology (ISN)/Renal Pathology Society (RPS) classification system divides glomerular disorders associated with SLE into six different classes based upon kidney biopsy histopathology:

• Class I – Minimal mesangial

• Class II – Mesangial proliferative lupus nephritis

• Class III – Focal lupus nephritis

• Class IV – Diffuse lupus nephritis

• Class V – Lupus membranous nephropathy

• Class VI – Advanced sclerosing

Benlysta (belimumab) is a B-lymphocyte stimulator (BLyS)-specific inhibitor indicated for the treatment of patients 5 years of age and older with active systemic lupus erythematosus (SLE) who are receiving standard therapy and for patients 5 years of age and older with active lupus nephritis who are receiving standard therapy.

Lupkynis (voclosporin) is a calcineurin-inhibitor immunosuppressant indicated in combination with a background immunosuppressive therapy regimen for the treatment of adult patients with active lupus nephritis.

Saphnelo (anifrolumab-fnia) is a type I interferon (IFN) receptor antagonist indicated for the treatment of adult patients with moderate to severe systemic lupus erythematosus (SLE), who are receiving standard therapy.

POLICY

Prior authorization is required.

The use of samples by an individual will not be considered current or stable therapy to satisfy Medical Policy Requirements.

Initial Criteria

Benlysta (belimumab) may be considered medically necessary when ALL of the following criteria are met:

1. ONE of the following:

   1. The individual has a documented diagnosis of active systemic lupus erythematosus (SLE) WITHOUT active lupus nephritis and ALL of the following:

      1. The individual is 5 years of age or older

         ;

      2. The individual has positive autoantibody test results [positive antinuclear antibody (ANA ≥1:80) and/or a positive or elevated anti-dsDNA (Farr assay, Crithidia luciliae assay, ELISA or Fluorescent beads)];

      3. The individual has at least threeof the following SLE diagnostic criteria:

         1. Malar rash;

         2. Discoid rash;

         3. Photosensitivity;

         4. Oral ulcers;

         5. Arthritis;

         6. Serositis (i.e. pleuritis/pericarditis);

         7. Kidney

            disorder (i.e. persistent proteinuria >500mg/24hr and/or greater than 3+ if quantitation not performed; cellular casts);

         8. Hematologic disorder (i.e. hemolytic anemia with reticulocytosis, leukopenia, lymphopenia, or thrombocytopenia); OR

         9. Immunologic disorder (i.e. positive finding of antiphospholipid antibodies or anti-Sm antibodies);

      4. The individual is currently receiving and will continue standard of care SLE treatment (i.e. corticosteroids, hydroxychloroquine, azathioprine, methotrexate, cyclosporine, cyclophosphamide, or mycophenolate) in combination with the requested agent;

      5. ONE of the following:

         1. The individual has tried and had an inadequate response (seePolicy Guidelines) to hydroxychloroquine; OR

         2. The individual has a hypersensitivity or FDA-labeled contraindication to hydroxychloroquine; AND

      6. ONE of the following:

         1. The individual has tried and had an inadequate response (see Policy Guidelines) to a corticosteroid or an immunosuppressive agent (i.e. azathioprine, methotrexate, cyclophosphamide, mycophenolate); OR

         2. The individual has a documented intolerance, hypersensitivity, or FDA-labeled contraindication to ALL standard of care SLE treatments listed above;OR

   2. The individual has a documented diagnosis of active lupus nephritis (LN) and ALL of the following:

      1. The individual is 5 years of age or older;

      2. BOTH of the following:

         1. The individual has a clinical diagnosis of SLE; AND

         2. The individual has documented LN Class III, Class IV, or Class V confirmed by kidney biopsy; AND

      3. The individual is currently receiving, or will receive, standard therapy for lupus nephritis (i.e., corticosteroids, immunosuppressive therapy in combination the requested agent);

2. The individual does not have or has not had severe active central nervous system lupus (i.e., seizures, psychosis, organic brain syndrome, cerebrovascular accident, cerebritis, CNS vasculitis) requiring therapeutic intervention within the past 60 days;

3. The prescriber is a specialist or has consulted with a specialist in an area of the individual's diagnosis (i.e., rheumatologist, nephrologist);

4. The requested agent will not be used in combination with another immunomodulatory agent (i.e. TNF inhibitors, JAK inhibitors, IL-4 inhibitors);

5. The individual does not have any FDA-labeled contraindication(s) to therapy with the requested agent; AND

6. The prescribed dosage is within the program quantity limits based on FDA approved labeled dosage.

Length of Approval: 6 months

Renewal Criteria

Benlysta (belimumab) may be approved for RENEWAL when ALL of the following criteria are met:

1. The individual has been previously approved for therapy with the requested agent through the BCBSMS PA process;

2. ONE of the following:

   1. The individual has a documented diagnosis of active systemic lupus erythematosus (SLE) WITHOUT active lupus nephritis (LN) and BOTH of the following:

      1. The individual has documented clinical improvement indicating a therapeutic response (i.e., reduction in global disease activity, no significant worsening of any organ system, no overall worsening of condition, etc.); AND

      2. ONE of the following:

         1. The individual is currently utilizing and will continue standard of care SLE treatment (i.e., corticosteroids, hydroxychloroquine, azathioprine, methotrexate, cyclophosphamide, mycophenolate); OR

         2. The individual has a documented intolerance or FDA labeled contraindication to ALL standard SLE treatments listed above; OR

   2. The individual has a documented diagnosis of active LN and BOTH of the following:

      1. The individual has documented clinical improvement indicating a therapeutic response (i.e., reduction in proteinuria, improvement or stabilization of serum creatinine, maintenance or improvement in eGFR, etc.); AND

      2. The individual will continue to receive standard therapy for lupus nephritis (i.e., corticosteroids, mycophenolate, cyclophosphamide);

3. The individual does not have or has not had severe active central nervous system lupus (i.e., seizures, psychosis, organic brain syndrome, cerebrovascular accident, cerebritis, CNS vasculitis) requiring therapeutic intervention within the past 60 days;

4. The prescriber is a specialist or has consulted with a specialist in an area of the individual's diagnosis (i.e., rheumatologist, nephrologist);

5. The requested agent will not be used in combination with another immunomodulatory agent (i.e. TNF inhibitors, JAK inhibitors, IL-4 inhibitors);

6. The individual does not have any FDA-labeled contraindication(s) to therapy with the requested agent; AND

7. The prescribed dosage is within the program quantity limits based on FDA approved labeled dosage.

Length of Approval: 12 months Benlysta (belimumab) is considered investigational when used for any other indication including, but not limited to, treatment of any of the following:

1. Severe active central nervous system lupus (including seizures that are attributed to CNS lupus, psychosis, organic brain syndrome, cerebrovascular accident, cerebritis, or CNS vasculitis) requiring therapeutic intervention within 60-days of belimumab initiation);

2. Use in combination with other biologics.

Lupkynis (voclosporin) and Saphnelo (anifrolumab-fnia) are considered not medically necessary as other formulary alternatives are covered by the Plan for treatment of lupus nephritis and systemic lupus erythematosus.

Services related to delivery and/or administration of a medication which have not been approved through the BCBSMS PA review process will be considered not medically necessary.

POLICY EXCEPTIONS

State Health Plan (State and School Employees) Participants

POLICY GUIDELINES

The coverage guidelines outlined in the Medical Policy Manual should not be used in lieu of the Member's specific benefit plan language.

Medically Necessary is defined as those services, treatments, procedures, equipment, drugs, devices, items or supplies furnished by a covered Provider that are required to identify or treat a Member's illness, injury or Mental Health Disorders, and which Company determines are covered under this Benefit Plan based on the criteria as follows in A through D:

A.  consistent with the symptoms or diagnosis and treatment of the Member's condition, illness, or injury; and

B.  appropriate with regard to standards of good medical practice; and

C.  not solely for the convenience of the Member, his or her Provider; and

D.  the most appropriate supply or level of care which can safely be provided to Member. When applied to the care of an Inpatient, it further means that services for the Member's medical symptoms or conditions require that the services cannot be safely provided to the Member as an Outpatient.

For the definition of medical necessity, “standards of good medical practice” means standards that are based on credible scientific evidence published in peer-reviewed medical literature generally recognized by the relevant medical community, and physician specialty society recommendations, and the views of medical practitioners practicing in relevant clinical areas and any other relevant factors. BCBSMS makes no payment for services, treatments, procedures, equipment, drugs, devices, items or supplies which are not documented to be Medically Necessary. The fact that a Physician or other Provider has prescribed, ordered, recommended, or approved a service or supply does not in itself, make it Medically Necessary.

BCBSMS may request medical records for determination of medical necessity. When medical records are requested, letters of support and/or explanation are often useful, but are not sufficient documentation unless all specific information needed to make a medical necessity determination is included.

Investigative is defined as the use of any treatment procedure, facility, equipment, drug, device, or supply not yet recognized as a generally accepted standard of good medical practice for the treatment of the condition being treated and; therefore, is not considered medically necessary. For the definition of Investigative, “generally accepted standards of medical practice” means standards that are based on credible scientific evidence published in peer-reviewed medical literature generally recognized by the relevant medical community, and physician specialty society recommendations, and the views of medical practitioners practicing in relevant clinical areas and any other relevant factors. In order for equipment, devices, drugs or supplies [i.e, technologies], to be considered not investigative, the technology must have final approval from the appropriate governmental bodies, and scientific evidence must permit conclusions concerning the effect of the technology on health outcomes, and the technology must improve the net health outcome, and the technology must be as beneficial as any established alternative and the improvement must be attainable outside the testing/investigational setting.

Medication Failure

Medication failure is defined as disease progression at generally accepted doses (≥3 months use) as appropriate for disease state being treated. Dosages below the recommended dose for the specific condition being treated and/or experience of common side effects of medication will not be considered medication failure for the purpose of this review.

BCBSMS determines patient medication trial and adherence by a review of pharmacy claims data over the preceding twelve months. Additional information may be requested on a case-by-case basis to allow for proper review. If member is new to BCBSMS and pharmacy records are needed to confirm medication trials and adherence, it is the responsibility of the member and/or requesting provider to obtain said records and to submit them to BCBSMS upon request. Medical records from the provider that list previously prescribed medications will not be sufficient to show medication trials or adherence.

POLICY HISTORY

11/01/2016: New policy added. Policy number L.5.01.507.

02/07/2017: Policy reviewed and approved by Pharmacy & Therapeutics (P&T) Committee.

07/01/2017: Policy statement revised to remove the following criteria: SLE is active as evidenced by a SELENA-SLEDAI score of ≥6 while on current treatment regimen. Added the following criteria: The patient has 3 other SLE diagnostic criteria (i.e. malar rash, discoid rash, photosensitivity, oral ulcers, nonerosive arthritis, serositis (e.g. pleuritis/pericarditis), renal disorder [e.g. persistent proteinuria >0.5 grams/day or cellular casts], hematologic disorder [e.g. hemolytic anemia (with reticulocytosis), leukopenia, lymphopenia, or thrombocytopenia], and/or immunologic disorder (e.g. positive finding of antiphospholipid antibodies or anti-Sm antibodies).

12/04/2017: Policy statement criteria updated to change "anti-dsDNA (≥30 IU/mL)" to "positive or elevated anti-dsDNA (Farr assay, Crithidia luciliae essay, ELISA or Fluorescent beads)." Policy criteria for initial and renewal evaluation updated to add dosage of 200 mg subcutaneously once weekly.

02/06/2018: Policy reviewed and approved by Pharmacy & Therapeutics (P&T) Committee.

02/05/2019: Policy reviewed and approved by Pharmacy & Therapeutics (P&T) Committee. Added statement to perform a formulary drug search on the patient's member ID to ensure the prescription drug is covered under their benefit plan. The medication(s) in this policy may not be covered under a specific member's benefit plan. Policy description revised and updated with FDA approved indications. For continued authorization, criteria updated to remove statement that the patient does not have any FDA labeled contraindications to the requested agent. Sources section updated. Effective 01/01/2019.

11/01/2020: Policy reviewed and approved by Pharmacy & Therapeutics (P&T) Committee. Policy description updated regarding FDA approved indications. Policy section updated to add that the use of samples by a Member will not be considered current or stable therapy for purposes of Medical Policy review. Medically necessary criteria updated to change "patient" to "member" and regarding FDA labeled dosage. Added statement that Benlysta is considered investigational when used to treat the conditions listed. Policy Exceptions statement re-worded. Policy Guidelines updated to define medication failure and to change "Nervous/Mental Conditions" to "Mental Health Disorders." Sources updated.

10/20/2021: Policy title changed from "Benlysta (belimumab)" to "Systemic Lupus Erythematosus (SLE) & Lupus Nephritis (LN)." Added Lupkynis (voclosporin) to the top of the policy. Policy description updated regarding systemic lupus erythematosus and to add indications for Lupkynis (voclosporin). Policy section updated to revise initial and renewal criteria for Benlysta (belimumab). Added policy statements for Lupkynis (voclosporin) and for services not approved through the BCBSMS PA review process. Policy Guidelines updated regarding BCBSMS request for medical records and to define medication failure. Sources updated.

07/01/2022: Policy description updated regarding indication for Saphnelo (anifrolumab-fnia). Policy statement updated to add Saphnelo (anifrolumab-fnia) as not medically necessary for treatment of Systemic Lupus Erythematosus. Sources updated. Code Reference section updated to add HCPCS code J0491 as not medically necessary.

02/01/2023: Policy Exceptions updated to add the following: State Health Plan (State and School Employees): The prescription drug(s) in this medical policy may be covered under a prescription drug benefit plan administered by the State Health Plan’s Pharmacy Benefit Manager. Please perform a formulary drug search at https://www.dfa.ms.gov/cvs-caremark and submit any required Prior Authorization Requests for coverage determination to the Plan’s Pharmacy Benefit Manager. Services related to delivery and/or administration of a medication determined to be not medically necessary will also be considered not medically necessary. Services related to delivery and/or administration of a self-administered drug are not covered.

07/01/2023: Policy Exceptions updated regarding State Health Plan (State and School Employees) Participants.

03/20/2025: Policy reviewed and approved by the Pharmacy & Therapeutics (P&T) Committee. Policy description updated regarding indications for Benlysta (belimumab). Policy statement revised to state that the use of samples by an individual will not be considered current or stable therapy to satisfy Medical Policy requirements. Medically necessary criteria updated regarding SLE diagnostic criteria, treatment failure, contraindications, standard therapy for lupus nephritis, and combination therapy. Renewal criteria revised regarding standard therapy for lupus nephritis and combination therapy. Revised policy statement to state that Benlysta (belimumab) is considered investigational when used for any other indication including, but not limited to, treatment of any of the listed conditions. Sources updated.

SOURCE(S)

1. Benlysta prescribing information. GlaxoSmithKline. June 2024. Last accessed February 2025.

2. Bomback AS, Appel GB.

   Lupus nephritis: Diagnosis and classification. UpToDate, Connor RF (Ed). Last updated January 2024. Last accessed February 2025. https://www.uptodate.com/contents/lupus-nephritis-diagnosis-and-classification

3. Lupkynis prescribing information. Aurinia Pharma U.S., Inc. December 2024. Last accessed February 2025.

4. Saphnelo prescribing information. AstraZeneca Pharmaceuticals LP. August 2024. Last accessed February 2025.

5. Wallace DJ, Gladman DD. Clinical manifestations and diagnosis of systemic lupus erythematosus. UpToDate, Connor RF (Ed). Last updated February 2025. Last accessed February 2025. https://www.uptodate.com/contents/systemic-lupus-erythematosus-in-adults-clinical-manifestations-and-diagnosis

CODE REFERENCE

This may not be a comprehensive list of procedure codes applicable to this policy.

The code(s) listed below are ONLY medically necessary if the procedure is performed according to the "Policy" section of this document.

Medically Necessary Codes

  Not Medically Necessary Codes

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