Coverage Policy Manual
Policy #: 2022012
Category: Pharmacy
Initiated: July 2022
Last Review: June 2026
Anifrolumab-fnia (e.g., Saphnelo)
Description:
Anifrolumab-fnia (e.g., Saphnelo) is a first-in-class type 1 interferon (type I IFN) receptor antagonist indicated for the treatment of moderate to severe systemic lupus erythematosus (SLE) in adult individuals. It is a human immunoglobulin. gamma 1 kappa (IgG1κ) monoclonal antibody that selectively binds to subunit 1 of type I IFN receptor (IFNAR1). This inhibits type I IFN signaling, causing the biological activity of the type 1 IFNs to be blocked.  Inhibition of type 1 IFN blocks plasma cell differentiation and normalizes peripheral T-cell subsets.  Up to 80% of adults with SLE have increased type 1signaling, which is associated with increased disease activity and severity.  
 
The American College of Rheumatology (ACR) uses the ACR classification criteria to diagnose an individual with SLE. The ACR requires 4 of these 11 criteria simultaneously or in succession for an individual to be classified as having SLE: malar rash, discoid rash, photosensitivity, oral ulcers, arthritis, serositis, renal disorders, neurological disorder, hematological disorder, immunological disorder, and anti-nuclear antibody.
 
Regulatory Status
 
Anifrolumab–fnia (e.g., Saphenlo) was approved by the Food and Drug Administration (FDA) on July 30, 2021, for the treatment of moderate to severe SLE in adult individuals who are receiving standard therapy.  This approval was based on combined data from 3 randomized, double-blind, placebo-controlled trials (TULIP-1, TULIP-2, and MUSE).  In these studies, more individuals who received Saphnelo in addition to standard therapy had improvement in overall lupus disease activity, skin and joint manifestations, and steroid use.
 
One of the most common and serious complications of systemic lupus erythematosus is lupus nephritis (LN), or kidney inflammation. If SLE is poorly controlled, LN may lead to irreversible kidney damage and the eventual need for dialysis or kidney transplant.  Anifrolumab-fnia (e.g., Saphnelo) has not been evaluated in individuals with severe active lupus nephritis or severe active central nervous system lupus, and therefore, not recommended in these situations FDS guidelines.
 
Coding
 
See CPT/HCPCS Code section below.
Policy/
Coverage:
Prior Approval is required for Anifrolumab-fnia.
 
The initial use of this drug requires documentation of direct physician (MD/OD) involvement in the ordering and evaluation as well as a signature in the medical records submitted for prior approval.
 
Anifrolumab-fnia subcutaneous (e.g., Saphnelo Pen) is not covered under the medical benefit. Please check the member’s pharmacy benefit for coverage.
 
INITIAL AND CONTINUATION APPROVAL will be for duration of the treatment course or 12 months (whichever comes first). Approval timeframes may differ for members/participants of Self-Insured plans.
 
Effective August 19, 2026
 
Meets Primary Coverage Criteria Or Is Covered For Contracts Without Primary Coverage Criteria
 
Anifrolumab-fnia (e.g., Saphenlo) intravenous infusion meets member benefit certificate Primary Coverage Criteria that there be scientific evidence of effectiveness in improving health outcomes or for members with contracts without Primary Coverage Criteria, is considered Medically Necessary and is covered, when ALL the following criteria are met:
 
 
INITIAL APPROVAL:
 
1. Individual is aged 18 years or older (Saphnelo, 2026); AND
2. Individual has a diagnosis of active moderate-severe systemic lupus erythematosus (SLE) diagnosed by specialist; AND
3. Individual does not have a severe active central nervous system lupus or severe active class III, IV or V lupus nephritis diagnosed by nephrologist or rheumatologist (Saphnelo, 2026); AND
4. Medical records (such as chart notes, lab reports) are provided documenting the presence of autoantibodies relevant to SLE (for example, ANA, anti-ds DNA, anti-Sm, antiphospholipid antibodies, complement proteins); AND
5. Individual is currently continuing antimalarial therapy (e.g., hydroxychloroquine) or antimalarial therapy is contraindicated; AND
6. Disease remains active while on corticosteroids, NSAIDs, or immunosuppressants and individual will be using anifrolumab in combination with standard therapy (for example, corticosteroids, antimalarials, and/or immunosuppressants [but not other biologics]); AND
7. Individual is not using the medication in combination with other biologic medication, for example: B Lymphocyte Stimulator Inhibitors (such as belimumab), TNF inhibitors (such as adalimumab, certolizumab, etanercept, golimumab), IL inhibitors (such as reslizumab, depemokimab, benralizumab, mepolizumab) B cell inhibitors (such as rituximab or ocrelizumab), and Selective Co-stimulation modulators (such as abatacept).
 
AUTHORIZATION RENEWAL:
 
1. Condition stable or improved with treatment; AND
2. Manageable or no side effects;AND
3. Individual is using in combination with standard therapy (for example, corticosteroids, antimalarials, and/or immunosuppressants; AND
4. Individual is not using the medication in combination with other biologic for example: TNF inhibitors, IL inhibitors, B cell inhibitors, and Selective Co-stimulation modulators.
 
Does Not Meet Primary Coverage Criteria Or Is Not Covered For Contracts Without Primary Coverage Criteria  
 
Anifrolumab-fnia (e.g., Saphenlo), for any indication or circumstance not described above, does not meet member benefit certificate Primary Coverage Criteria that there be scientific evidence of effectiveness in improving health outcomes and is not covered.
 
For members with contracts without Primary Coverage Criteria,, anifrolumab-fnia (e.g., Saphenlo) for any indication or circumstance not described above, is considered not Medically Necessary and is not covered or is investigational. Not Medically Necessary or Investigational services are specific contract exclusions in most member benefit certificates of coverage.
 
POLICY GUIDELINES
 
Prescribing physician is responsible for ensuring individual does not have human immunodeficiency virus (HIV) infection, hepatitis B virus infection, or hepatitis C virus infection (Bruce, 2023)
 
DOSING AND ADMINISTRATION
 
For FDA labeled indications, anifrolumab-fnia (e.g., Saphenlo) must be dosed in accordance with the indication specific recommended dose per FDA label unless otherwise specified in the dosage and administration section.
 
The recommended dose of anifrolumab is 300 mg every 4 weeks.
 
Anifrolumab is available as a 300 mg/2 mL (150 mg/mL) in a single dose vial.
 
Anifrolumab should be administered as an intravenous infusion by a healthcare professional.
 
Please refer to a separate policy on Site of Care or Site of Service Review (policy #2018030) for pharmacologic/biologic medications.
 
Effective June 18, 2025 to August  18, 2026
 
Meets Primary Coverage Criteria Or Is Covered For Contracts Without Primary Coverage Criteria
 
Anifrolumab-fnia (e.g., Saphenlo) intravenous infusion meets member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes when ALL the following criteria are met:
 
For FDA labeled indications, anifrolumab-fnia (e.g., Saphenlo) must be dosed in accordance with the indication specific recommended dose per FDA label unless otherwise specified in the dosage and administration section.
 
INITIAL APPROVAL STANDARD REVIEW for up to 12 months:
 
1. Individual is aged 18 years or older (Saphnelo, 2024); AND
2. Individual has diagnosis of active moderate-severe systemic lupus erythematosus (SLE) (Saphnelo, 2024) supported by the submitted medical records as seen by the following:
a. Individual has antinuclear antibodies (ANA) at a titer of greater than or equal to 1:80 or anti-dsDNA antibodies greater than or equal to 30 IU/mL; AND
b. Individual has at least one clinical criterion from the 2019 EULAR/ACR guidelines AND has a score greater than or equal to 10 on the additive criteria scale from the 2019 EULAR/ACR guidelines (see policy guidelines) (EULAR/ACR, 2019);OR
c. Individual has at least four SLICC criteria (see policy guidelines), with at least one clinical criterion AND one immunologic criterion. (2012 Petri M, et. al.); AND
3. SLE remains active and moderate-severe while receiving standard therapy alone or in combination (FDA, 2011):
a. Glucocorticoids [e.g., prednisone, methylprednisolone, dexamethasone]; OR
b. Anti-malarial [e.g., hydroxychloroquine, chloroquine]; OR
c. Immunosuppressants [e.g., azathioprine, methotrexate, mycophenolate, cyclosporine, cyclophosphamide, leflunomide ];AND
4. Individual must have failed, not tolerated, or have a contraindication to a trial (greater than or equal to  3 months) of hydroxychloroquine/chloroquine(KDIGO 2021); AND
5. Individual is not using the medication in combination with other biologic, for example: TNF inhibitors (i.e., Humira, Cimzia etc.), IL inhibitors (i.e., Nucala, Tremfya etc.), B cell inhibitors (i.e., Rituxan, Riabini and Truxima), and Selective Co-stimulation modulators (i.e., Orencia): AND
6. Individual does not have severe active central nervous system lupus (such as psychosis or seizures) (Saphnelo, 2024) AND/OR severe active lupus nephritis (defined as proteinuria greater than 6 gm/d, serum creatinine greater than 2.5 mg/dl, or requiring dialysis); (Saphnelo, 2024; Bruce, 2023).   
 
CONTINUED APPROVAL for 12 months:
 
1. Documentation is provided showing improvement in disease activity following treatment indicating a therapeutic response; AND
2. Individual has no evidence of severe active central nervous system lupus (such as psychosis or seizures);AND
3. Individual has documentation (statement or as evidenced by labs) that there is no evidence of severe active lupus nephritis (defined as proteinuria greater than 6 gm/d, serum creatinine greater than 2.5 mg/dl, or requiring dialysis);AND
4. Individual is using in combination with standard therapy (for example, corticosteroids, antimalarials, and/or immunosuppressants; AND
5. Individual is not using the medication in combination with other biologic for example: TNF inhibitors, IL inhibitors, B cell inhibitors, and Selective Co-stimulation modulators.
 
Policy Guidelines
 
Prescribing physician is responsible for ensuring individual does not have human immunodeficiency virus (HIV) infection, hepatitis B virus infection, or hepatitis C virus infection (Bruce, 2023)
 
2019 EULAR/ACR Guideline Criteria
1. Do not count a criterion if there is a more likely explanation than SLE.
2. Occurrence of a criterion on at least one occasion is sufficient.
3. SLE classification requires at least one clinical criterion and greater than or equal to 10 points.
4. Criteria need not occur simultaneously.
5. Within each domain, only the highest weighted criterion is counted to the total score.
 
Clinical Domains and criteria                        Weight
Constitutional
Fever                                                              2
Hematologic
Leukopenia                                                     3  
Thrombocytopenia                                           4
Autoimmune Hemolysis                                   4
Neuropsychiatric
Delirium                                                          2
Psychosis                                                      3
Mucocutaneous
Non-scarring alopecia                                      2
Oral ulcers                                                     2
Subacute cutaneous OR discoid lupus             4
Acute cutaneous lupus                                   6
Serosal
Pleural or pericardial effusion                           5
Acute pericarditis                                           6
Musculoskeletal
Joint involvement                                              6
Renal
Proteinuria greater than 0.5/24h                         4
Renal biopsy Class II or V lupus nephritis           8
Renal biopsy Class III or IV lupus nephritis         10
 
Immunology domains and Criteria               Weight
Antiphospholipid Antibodies
Anti-Cardiolipin antibodies OR
Anti-β2GP1 antibodies OR
Lupus anticoagulant                                         2
Complement Proteins
Low C3 or low C4                                             3
Low C3 and low C4                                          4
SLE-specific antibodies
Anti-dsDNA antibody OR
Anti-Smith antibody                                          6
 
2012 SLICC Criteria (2012 Petri M, et. al.)
The SLICC criteria for SLE classification require:
1. Fulfillment of at least 4 criteria, with at least one clinical criterion AND one immunologic criterion; OR
2. Lupus nephritis as the sole clinical criterion in the presence of ANA or anti-dsDNA antibodies.
 
Clinical Criteria:
1. Acute cutaneous lupus
2. Chronic cutaneous lupus
3. Oral ulcers: palate
4. Nonscarring alopecia (diffuse thinning or hair fragility with visible broken hairs)
5. Synovitis involving two or more joints, characterized by swelling or effusion OR tenderness in two or more joints and thirty minutes or more of morning stiffness.
6. Serositis
7. Renal
8. Neurologic
9. Hemolytic anemia
10. Leukopenia (< 4000/mm3 at least once)
11. Thrombocytopenia (<100,000/mm3) at least once
 
Immunological Criteria:
1. ANA above laboratory reference range
2. Anti-dsDNA above laboratory reference range, except ELISA: twice above laboratory
3. Anti-Sm
4. Antiphospholipid antibody: any of the following
5. Low complement
6. Direct Coombs test in the absence of hemolytic anemia
 
Dosing and Administration
Dosing per FDA Guidelines unless otherwise specified below.
 
The recommended dose of anifrolumab is 300 mg every 4 weeks.
 
Anifrolumab is available as a 300 mg/2 mL (150 mg/mL) in a single dose vial.
 
Anifrolumab should be administered as an intravenous infusion by a healthcare professional.
 
Please refer to a separate policy on Site of Care or Site of Service Review (policy #2018030) for pharmacologic/biologic medications.
 
Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria  
 
Anifrolumab-fnia (e.g., Saphenlo), for any indication or circumstance not described above, does not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes.
 
For members with contracts without primary coverage criteria, anifrolumab-fnia for any indication or circumstance not described above are considered investigational. Investigational services are specific contract exclusions in most member benefit certificates of coverage.
 
Effective June 12, 2024 to June 17, 2025
 
Meets Primary Coverage Criteria Or Is Covered For Contracts Without Primary Coverage Criteria
 
Anifrolumab-fnia (e.g., Saphenlo) intravenous infusion meets member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes when ALL the following criteria are met:
 
INITIAL APPROVAL STANDARD REVIEW for up to 12 months:
 
1. Individual is aged 18 years or older; AND
2. Individual has diagnosis of active moderate-severe systemic lupus erythematosus (SLE) supported by the submitted medical records as seen by the following:
a. Individual has antinuclear antibodies (ANA) at a titer of > 1:80;AND has at least one clinical criterion from the 2019 EULAR/ACR guidelines AND has a score > 10 on the additive criteria scale from the 2019 EULAR/ACR guidelines (see policy guidelines) (EULAR/ACR, 2019);OR
b. Individual has at least four SLICC criteria (see policy guidelines), with at least one clinical criterion AND one immunologic criterion. (2012 Petri M, et. al.) OR
c. Individual has lupus nephritis in the presence of ANA or anti-dsDNA antibodies; AND
3. SLE remains active and moderate-severe while receiving standard therapy alone or in combination (FDA, 2011):
a. Glucocorticoids [e.g., prednisone, methylprednisolone, dexamethasone]; OR
b. Anti-malarial [e.g., hydroxychloroquine, chloroquine]; OR
c. Immunosuppressants [e.g., azathioprine, methotrexate, mycophenolate, cyclosporine, cyclophosphamide, leflunomide ];AND
4. Individual must have failed, not tolerated, or have a contraindication to a trial (>3 months) of hydroxychloroquine/chloroquine(KDIGO 2021); AND
5. Individual is not using the medication in combination with other biologic, for example: TNF inhibitors (i.e., Humira, Cimzia etc), IL inhibitors (i.e., Nucala, Tremfya etc), B cell inhibitors (i.e., Rituxan, Riabini and Truxima), and Selective Co-stimulation modulators (i.e., Orencia): AND
6. Individual has no evidence of severe active central nervous system lupus (such as psychosis or seizures) (FDA label, 2021); AND
7. Individual has documentation (statement or as evidenced by labs) that there is no evidence of severe active lupus nephritis (defined as proteinuria greater than 6 gm/d, serum creatinine greater than 2.5 mg/dl, or requiring dialysis); (FDA Label,2021); AND
8. The individual has no evidence of human immunodeficiency virus (HIV) infection, hepatitis B virus infection, or hepatitis C virus infection. AND
9. Must be dosed in accordance with the FDA label.
 
CONTINUED APPROVAL for 1 year:
1. Documentation is provided showing improvement in disease activity following treatment indicating a therapeutic response; AND
2. Individual has no evidence of severe active central nervous system lupus (such as psychosis or seizures);AND
3. Individual has documentation (statement or as evidenced by labs) that there is no evidence of severe active lupus nephritis (defined as proteinuria greater than 6 gm/d, serum creatinine greater than 2.5 mg/dl, or requiring dialysis);AND
4. Individual is using in combination with standard therapy (for example, corticosteroids, antimalarials, and/or immunosuppressants; AND
5. Individual is not using the medication in combination with other biologic for example: TNF inhibitors, IL inhibitors, B cell inhibitors, and Selective Co-stimulation modulators; AND
6. Must be dosed in accordance with the FDA label.
 
Policy Guidelines
 
2019 EULAR/ACR Guideline Criteria
1. Do not count a criterion if there is a more likely explanation than SLE.
2. Occurrence of a criterion on at least one occasion is sufficient.
3. SLE classification requires at least one clinical criterion and greater than or equal to 10 points.
4.  Criteria need not occur simultaneously.
5. Within each domain, only the highest weighted criterion is counted to the total score.
 
Clinical Domains and criteria                        Weight
Constitutional
Fever                                                                       2
Hematologic
Leukopenia                                                             3  
Thrombocytopenia                                                  4
Autoimmune Hemolysis                                          4
Neuropsychiatric
Delirium                                                                   2
Psychosis                                                                3
Mucocutaneous
Non-scarring alopecia                                             2
Oral ulcers                                                               2
Subacute cutaneous OR discoid lupus                   4
Acute cutaneous lupus                                            6
Serosal
Pleural or pericardial effusion                                  5
Acute pericarditis                                                    6
Musculoskeletal
Joint involvement                                                    6
Renal
Proteinuria greater than 0.5/24h                             4
Renal biopsy Class II or V lupus nephritis               8
Renal biopsy Class III or IV lupus nephritis           10
 
Immunology domains and Criteria               Weight
Antiphospholipid Antibodies
Anti-Cardiolipin antibodies OR
Anti-β2GP1 antibodies OR
Lupus anticoagulant                                                2
Complement Proteins
Low C3 or low C4                                                    3
Low C3 and low C4                                                 4
SLE-specific antibodies
Anti-dsDNA antibody OR
Anti-Smith antibody                                                 6
 
2012 SLICC Criteria (2012 Petri M, et. al.)
The SLICC criteria for SLE classification require:
1. Fulfillment of at least 4 criteria, with at least one clinical criterion AND one immunologic criterion; OR
2. Lupus nephritis as the sole clinical criterion in the presence of ANA or anti-dsDNA antibodies.
 
Clinical Criteria:
1. Acute cutaneous lupus
2. Chronic cutaneous lupus
3. Oral ulcers: palate
4. Nonscarring alopecia (diffuse thinning or hair fragility with visible broken hairs)
5. Synovitis involving two or more joints, characterized by swelling or effusion OR tenderness in two or more joints and thirty minutes or more of morning stiffness.
6. Serositis
7. Renal
8. Neurologic
9. Hemolytic anemia
10. Leukopenia (< 4000/mm3 at least once)
11. Thrombocytopenia (<100,000/mm3) at least once
 
Immunological Criteria:
1. ANA above laboratory reference range
2. Anti-dsDNA above laboratory reference range, except ELISA: twice above laboratory
3. Anti-Sm
4. Antiphospholipid antibody: any of the following
5. Low complement
6. Direct Coombs test in the absence of hemolytic anemia
 
Dosing and Administration
Dosing per FDA Guidelines
 
The recommended dose of anifrolumab is 300 mg every 4 weeks.
 
Anifrolumab is available as a 300 mg/2 mL (150 mg/mL) in a single dose vial.
 
Anifrolumab should be administered as an intravenous infusion by a healthcare professional.
 
Please refer to a separate policy on Site of Care or Site of Service Review (policy #2018030) for pharmacologic/biologic medications.
 
Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria  
 
Anifrolumab-fnia (e.g., Saphenlo), for any indication or circumstance not described above, does not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes.
 
For members with contracts without primary coverage criteria, anifrolumab-fnia for any indication or circumstance not described above are considered investigational. Investigational services are specific contract exclusions in most member benefit certificates of coverage.
 
Effective January 2024
 
Meets Primary Coverage Criteria Or Is Covered For Contracts Without Primary Coverage Criteria
 
Anifrolumab-fnia (e.g., Saphenlo) intravenous infusion meets member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes when ALL the following criteria are met:
 
INITIAL APPROVAL STANDARD REVIEW for up to 12 months:
 
1. Individual is aged 18 years or older; AND
2. Individual has diagnosis of active moderate-severe systemic lupus erythematosus (SLE) supported by the submitted medical records as seen by the following:
a. Individual has antinuclear antibodies (ANA) at a titer of > 1:80;AND has at least one clinical criterion from the 2019 EULAR/ACR guidelines AND has a score > 10 on the additive criteria scale from the 2019 EULAR/ACR guidelines (see policy guidelines) (EULAR/ACR, 2019);OR
b. Individual has at least four SLICC criteria (see policy guidelines), with at least one clinical criterion AND one immunologic criterion. (2012 Petri M, et. al.) OR
c. Individual has lupus nephritis in the presence of ANA or anti-dsDNA antibodies; AND
3. SLE remains active and moderate-severe while receiving standard therapy alone or in combination (FDA, 2011):
a. Glucocorticoids [e.g., prednisone, methylprednisolone, dexamethasone]; OR
b. Anti-malarial [e.g., hydroxychloroquine, chloroquine]; OR
c. Immunosuppressants [e.g., azathioprine, methotrexate, mycophenolate, cyclosporine, cyclophosphamide, leflunomide ];AND
4. Individual must have failed, not tolerated, or have a contraindication to a trial (>3 months) of hydroxychloroquine/chloroquine(KDIGO 2021); AND
5. Individual is not using the medication in combination with other biologic, for example: TNF inhibitors (i.e., Humira, Cimzia etc), IL inhibitors (i.e., Nucala, Tremfya etc), B cell inhibitors (i.e., Rituxan, Riabini and Truxima), and Selective Co-stimulation modulators (i.e., Orencia): AND
6. Individual has no evidence of severe active central nervous system lupus (FDA label, 2021); AND
7. Individual has no evidence of severe active lupus nephritis (defined as proteinuria greater than 6 gm/d, serum creatinine greater than 2.5 mg/dl, or requiring dialysis); (FDA Label,2021); AND
8. The individual has no evidence of human immunodeficiency virus (HIV) infection, hepatitis B virus infection, or hepatitis C virus infection. AND
9. Must be dosed in accordance with the FDA label.
 
CONTINUED APPROVAL for 1 year:
1. Documentation is provided showing improvement in disease activity following treatment indicating a therapeutic response; AND
2. Individual has no evidence of severe active central nervous system lupus (such as psychosis or seizures);AND
3. Individual has no evidence of severe active lupus nephritis (defined as proteinuria greater than 6 gm/d, serum creatinine greater than 2.5 mg/dl, or requiring dialysis);AND
4. Individual is using in combination with standard therapy (for example, corticosteroids, antimalarials, and/or immunosuppressants; AND
5. Individual is not using the medication in combination with other biologic for example: TNF inhibitors, IL inhibitors, B cell inhibitors, and Selective Co-stimulation modulators; AND
6. Must be dosed in accordance with the FDA label.
 
Policy Guidelines
 
2019 EULAR/ACR Guideline Criteria
1. Do not count a criterion if there is a more likely explanation than SLE.
2. Occurrence of a criterion on at least one occasion is sufficient.
3. SLE classification requires at least one clinical criterion and greater than or equal to 10 points.
4.  Criteria need not occur simultaneously.
5. Within each domain, only the highest weighted criterion is counted to the total score.
 
Clinical Domains and criteria                        Weight
Constitutional
Fever                                                                       2
Hematologic
Leukopenia                                                             3  
Thrombocytopenia                                                  4
Autoimmune Hemolysis                                          4
Neuropsychiatric
Delirium                                                                   2
Psychosis                                                                3
Mucocutaneous
Non-scarring alopecia                                             2
Oral ulcers                                                               2
Subacute cutaneous OR discoid lupus                   4
Acute cutaneous lupus                                            6
Serosal
Pleural or pericardial effusion                                  5
Acute pericarditis                                                    6
Musculoskeletal
Joint involvement                                                    6
Renal
Proteinuria greater than 0.5/24h                             4
Renal biopsy Class II or V lupus nephritis               8
Renal biopsy Class III or IV lupus nephritis           10
 
Immunology domains and Criteria               Weight
Antiphospholipid Antibodies
Anti-Cardiolipin antibodies OR
Anti-β2GP1 antibodies OR
Lupus anticoagulant                                                2
Complement Proteins
Low C3 or low C4                                                    3
Low C3 and low C4                                                 4
SLE-specific antibodies
Anti-dsDNA antibody OR
Anti-Smith antibody                                                 6
 
2012 SLICC Criteria (2012 Petri M, et. al.)
The SLICC criteria for SLE classification require:
1. Fulfillment of at least 4 criteria, with at least one clinical criterion AND one immunologic criterion; OR
2. Lupus nephritis as the sole clinical criterion in the presence of ANA or anti-dsDNA antibodies.
 
Clinical Criteria:
1. Acute cutaneous lupus
2. Chronic cutaneous lupus
3. Oral ulcers: palate
4. Nonscarring alopecia (diffuse thinning or hair fragility with visible broken hairs)
5. Synovitis involving two or more joints, characterized by swelling or effusion OR tenderness in two or more joints and thirty minutes or more of morning stiffness.
6. Serositis
7. Renal
8. Neurologic
9. Hemolytic anemia
10. Leukopenia (< 4000/mm3 at least once)
11. Thrombocytopenia (<100,000/mm3) at least once
 
Immunological Criteria:
1. ANA above laboratory reference range
2. Anti-dsDNA above laboratory reference range, except ELISA: twice above laboratory
3. Anti-Sm
4. Antiphospholipid antibody: any of the following
5. Low complement
6. Direct Coombs test in the absence of hemolytic anemia
 
Dosing and Administration
Dosing per FDA Guidelines
 
The recommended dose of anifrolumab is 300 mg every 4 weeks.
 
Anifrolumab is available as a 300 mg/2 mL (150 mg/mL) in a single dose vial.
 
Anifrolumab should be administered as an intravenous infusion by a healthcare professional.
 
Please refer to a separate policy on Site of Care or Site of Service Review (policy #2018030) for pharmacologic/biologic medications.
 
Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria  
 
Anifrolumab-fnia (e.g., Saphenlo), for any indication or circumstance not described above, does not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes.
 
For members with contracts without primary coverage criteria, anifrolumab-fnia for any indication or circumstance not described above are considered investigational. Investigational services are specific contract exclusions in most member benefit certificates of coverage.
 
Effective March 2023 - December 2023
 
Meets Primary Coverage Criteria Or Is Covered For Contracts Without Primary Coverage Criteria
 
The use of anifrolumab-fnia intravenous infusion meets member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes for individuals with moderate to severe SLE and they meet ALL the following criteria:  
 
INITIAL APPROVAL STANDARD REVIEW for up to 12 months
    1. Individual is aged 18 years or older   AND
    2. Individual meets requirements for diagnosis of active moderate-severe systemic lupus erythematosus (SLE) either by 2019 EULAR/ACR classification criteria for SLE (ACR, 2019),[ documented by a SLEDAI-2K score greater than or equal to 6 while on current treatment regimen for SLE (Morand, 2020)], AND
    3. Documentation is provided that the individual has a positive anti-nuclear antibody (ANA) titer greater than or equal to 1:80 or anti dsDNA greater than or equal to 30 IU/mL (Morand 2020, EULAR/ACR 2019); AND
    4. SLE remains active and moderate-severe while receiving standard therapy (e.g., corticosteroids, aspirin, non-steroidal anti-inflammatory drugs [NSAIDs], anti-malarials [hydroxychloroquine, chloroquine], or non-biologic immunosuppressants [azathioprine, methotrexate, cyclosporine, oral cyclophosphamide]), alone or in combination therapy (FDA, 2011); AND
    5. Individual must have failed, not tolerated, or have a contraindication to a trial of belimumab, AND
    6. No evidence of severe active central nervous system lupus (FDA label, 2021); AND
    7. No evidence of active lupus nephritis (FDA Label,2021).
    8. Must be dosed in accordance with the FDA label.
 
CONTINUATION for 1 year:
Continuation for anifrolumab-fnia (e.g., Saphnelo) may be approved if all the following criteria are met:
    1. Documentation is provided showing improvement in disease activity following treatment with anifrolumab-fnia indicating a therapeutic response; AND
    2. Individual has no evidence of severe active central nervous system lupus (such as psychosis or seizures); AND
    3. Individual has no evidence of severe active lupus nephritis (defined as proteinuria greater than 6 gm/d, serum creatinine greater than 2.5 mg/dl, or requiring dialysis); AND
    4. Individual is using in combination with standard therapy (for example, corticosteroids, antimalarials, and/or immunosuppressants [will not be used with other biologics or cyclophosphamide]).
 
Dosing and Administration
Dosing per FDA Guidelines
 
The recommended dosing is 300 mg IV every 4 weeks.
 
Please refer to a separate policy on Site of Care or Site of Service Review (policy #2018030) for pharmacologic/biologic medications.
 
Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria  
 
The use of anifrolumab-fnia does not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes for any indication or circumstance other those outlined above, including:
    1. There is evidence of severe active central nervous system lupus (such as psychosis or seizures), OR
    2. The individual has evidence of severe active lupus nephritis (defined as proteinuria greater than 6 gm/d, serum creatinine greater than 2.5 mg/dl, or requiring dialysis); OR
    3. The individual is using in combination with another biologic (including, but not limited to, B-cell targeted therapies or belimumab), voclosporin, or cyclophosphamide, OR
    4. The individual has human immunodeficiency virus (HIV) infection, hepatitis B virus infection, or hepatitis C virus infection.
 
For members with contracts without primary coverage criteria, anifrolumab-fnia for any indication or circumstance other those outlined above are considered investigational.  Investigational services are specific contract exclusions in most member benefit certificates of coverage.
 
Effective July 1, 2022 to February 2023
 
Meets Primary Coverage Criteria Or Is Covered For Contracts Without Primary Coverage Criteria
 
The use of anifrolumab-fnia intravenous infusion meets member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness for patients with moderate to severe SLE and they meet ALL the following criteria:  
 
INITIAL APPROVAL STANDARD REVIEW for up to 12 months
  1. Individual is aged 18 years or older   AND
  2. Member meets requirements for diagnosis of active moderate-severe systemic lupus erythematosus (SLE) either by 2019 EULAR/ACR classification criteria for SLE (ACR, 2019),[ documented by a SLEDAI-2K score greater than or equal to 6 while on current treatment regimen for SLE (Morand, 2020)], AND
  3. Documentation is provided that the individual has a positive anti-nuclear antibody (ANA) titer greater than or equal to 1:80 or anti dsDNA greater than or equal to 30 IU/mL (Morand 2020, EULAR/ACR 2019); AND
  4. SLE remains active and moderate-severe while receiving standard therapy (e.g. corticosteroids, aspirin, non-steroidal anti-inflammatory drugs [NSAIDs], anti-malarials [hydroxychloroquine, chloroquine], or non-biologic immunosuppressants [azathioprine, methotrexate, cyclosporine, oral cyclophosphamide]), alone or in combination therapy (FDA, 2011); AND
  5. Member must have failed, not tolerated, or have a contraindication to a trial of belimumab, AND
  6. No evidence of severe active central nervous system lupus (FDA label, 2021); AND
  7. No evidence of active lupus nephritis (FDA Label,2021).
 
CONTINUATION for 1 year:
Continuation for anifrolumab-fnia (e.g., Saphnelo) may be approved if all the following criteria are met:
  1. Documentation is provided showing improvement in disease activity following treatment with anifrolumab-fnia indicating a therapeutic response; AND
  2. Individual has no evidence of severe active central nervous system lupus (such as psychosis or seizures); AND
  3. Individual has no evidence of severe active lupus nephritis (defined as proteinuria greater than 6 gm/d, serum creatinine greater than 2.5 mg/dl, or requiring dialysis); AND
  4. Individual is using in combination with standard therapy (for example, corticosteroids, antimalarials, and/or immunosuppressants [will not be used with other biologics or cyclophosphamide]).
 
Dosing
 
The recommended dosing is 300 mg IV every 4 weeks.
 
Please refer to a separate policy on Site of Care or Site of Service Review (policy #2018030) for pharmacologic/biologic medications.
 
Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria  
 
The use of anifrolumab-fnia does not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness for any indication or any circumstance other those outlined above, including:
  1. There is evidence of severe active central nervous system lupus (such as psychosis or seizures), OR
  2. The individual has evidence of severe active lupus nephritis (defined as proteinuria greater than 6 gm/d, serum creatinine greater than 2.5 mg/dl, or requiring dialysis); OR
  3. The individual is using in combination with another biologic (including, but not limited to, B-cell targeted therapies or belimumab), voclosporin, or cyclophosphamide, OR
  4. The individual has human immunodeficiency virus (HIV) infection, hepatitis B virus infection, or hepatitis C virus infection.
 
For members with contracts without primary coverage criteria, anifrolumab-fnia for any indication or circumstance other those outlined above are considered investigational.  Investigational services are specific contract exclusions in most member benefit certificates of coverage.
Rationale:
The safety and efficacy of SAPHNELO were evaluated in three 52-week treatment period, multicenter, randomized, double-blind, placebo-controlled studies [Trial 1 (Phase 2), MUSE [NCT01438489], Trial 2 (Phase 3) TULIP-1 [NCT02446912] and Trial 3 (Phase 3) TULIP-3 [NCT02446899]). Patients were diagnosed with SLE according to the American College of Rheumatology (1982 revised) classification criteria. All patients were ≥18 years of age and had moderate to severe disease, with a SLE Disease Activity Index 2000 (SLEDAI-2K) score ≥6 points, organ level involvement based on BILAG assessment, and a Physician’s Global Assessment [PGA] score ≥1, despite receiving standard SLE therapy consisting of either one or any combination of oral corticosteroids (OCS), antimalarials and/or immunosuppressants at baseline. Patients continued to receive their existing SLE therapy at stable doses during the clinical trials, with the exception of OCS (prednisone or equivalent) where tapering was a component of the protocol. Patients who had severe active lupus nephritis and patients who had severe active central nervous system lupus were excluded. The use of other biologic agents and cyclophosphamide were not permitted during the trials; patients receiving other biologic therapies were required to complete a wash-out period of at least 5 half-lives prior to enrollment. All three studies were conducted in North America, Europe, South America and Asia. Patients received anifrolumab-fnia or placebo, administered by intravenous infusion, every 4 weeks. Efficacy of SAPHNELO was established based on assessment of clinical response using the composite endpoints, the British Isles Lupus Assessment Group based Composite Lupus Assessment (BICLA) and the SLE Responder Index (SRI-4).
 
Trial 1 randomized 305 patients (1:1:1) who received anifrolumab-fnia, 300 mg or 1000 mg, or placebo (in addition to standard therapy) for up to 52 weeks. The primary endpoint was a combined assessment of the SRI-4 and the sustained reduction in OCS (<10 mg/day and <OCS dose at Week 1, sustained for 12 weeks) measured at week 24.  The primary endpoint was met in this trial.
 
Trial 2 randomized 457 patients (1:2:2) who received anifrolumab-fnia, 150 mg or 300 mg, or placebo for up to 52 weeks.  Trial 3 randomized 362 patients (1:2) who received 300 mg or anifrolumab-fnia or placebo.  For both studies, during weeks 8-40, patients with a baseline OCS dose to > 10 mg/day were required to taper OCS dose to <7.5 mg/day, unless there was worsening of disease activity. The primary endpoint for Trial 2 was improvement of disease activity evaluated at 52 weeks, measured by SRI-4.  The primary endpoint for Trial 3 was the same as Trial 2 but measured by BICLA. Trial 2 did not meet its primary endpoint, whereas Trial 3 did meet its primary endpoint.
  
In Trial 3, among the 47% of patients with a baseline OCS use ≥10 mg/day, anifrolumab-fnia demonstrated a statistically significant difference in the proportion of patients able to reduce OCS use by at least 25% to ≤7.5 mg/day at Week 40 and maintain the reduction through Week 52 (p-value = 0.004); 52% (45/87) of patients in the anifrolumab-fnia group versus 30% (25/83) in the placebo achieved this level of steroid reduction (difference 21% [95% CI 6.8, 35.7]). Consistent trends in favor of anifrolumab-fnia compared to placebo, on effect of reduction of OCS use, were observed in Trial 1 and 2, but the difference was not statistically significant.
 
2023 Update
In the blinded LTE study, patients continued anifrolumab 300 mg, switched from anifrolumab 150 mg to 300 mg, or were re-randomized from placebo to receive either anifrolumab 300 mg or to continue placebo, administered every 4 weeks. Primary comparisons in the LTE study were between patients who received anifrolumab 300 mg or placebo throughout the TULIP and LTE studies. For rare safety events, comparisons included patients who received any anifrolumab dose during TULIP or LTE. When exposure differed, exposure-adjusted incidence rates (EAIRs) per 100 patient-years were calculated.
 
In the LTE study, EAIRs of serious adverse events (SAEs) were 8.5 with anifrolumab compared with 11.2 with placebo; likewise, EAIRs of AEs leading to treatment discontinuation were 2.5 versus 3.2, respectively. EAIRs of non-opportunistic serious infections were comparable between groups (3.7 with anifrolumab versus 3.6 with placebo). Exposure-adjusted event rates of COVID-related AEs, including asymptomatic infections, were 15.5 with anifrolumab compared with 9.8 with placebo. No COVID-related AEs occurred in fully vaccinated individuals. EAIRs of malignancy and major acute cardiovascular events were low and comparable between groups. Anifrolumab was associated with lower cumulative glucocorticoid use and greater mean improvement in the SLE Disease Activity Index 2000, compared with placebo.
 
This LTE study represents the longest placebo-controlled clinical trial performed in SLE to date. No new safety findings were identified in the LTE study, supporting the favorable benefit-risk profile of anifrolumab for patients with moderate-to-severe SLE receiving standard therapy. (Kalunian KC, Furie R, Morand EF, 2023)
 
2024 Update
Annual policy review completed with a literature search using the MEDLINE database through March 2024. No new literature was identified that would prompt a change in the coverage statement.
 
2025 Update
Patients with moderate to severe SLE were enrolled in TULIP-1 and TULIP-2 and received intravenous anifrolumab or placebo alongside standard therapy. Whole-blood expression of 18 017 genes using genome-wide RNA sequencing (RNA-seq) (pooled TULIP; anifrolumab, n=244; placebo, n=258) and 184 plasma proteins using Olink and Simoa panels (TULIP-1; anifrolumab, n=124; placebo, n=132) were analysed. We compared treatment groups via gene set enrichment analysis using MetaBase pathway analysis, blood transcriptome modules, in silico deconvolution of RNA-seq and longitudinal linear mixed effect models for gene counts and protein levels.
 
Compared with placebo, anifrolumab modulated >2000 genes by week 24, with overlapping results at week 52, and 41 proteins by week 52. IFNAR1 blockade with anifrolumab downregulated multiple type I and II IFN-induced gene modules/pathways and type III IFN-λ protein levels, and impacted apoptosis-associated and neutrophil extracellular traps-(NET)osis-associated transcriptional pathways, innate cell activating chemokines and receptors, proinflammatory cytokines and B-cell activating cytokines. In silico deconvolution of RNA-seq data indicated an increase from baseline of mucosal-associated invariant and γδT cells and a decrease of monocytes following anifrolumab treatment.
 
Type I IFN blockade with anifrolumab modulated multiple inflammatory pathways downstream of type I IFN signalling, including apoptotic, innate and adaptive mechanisms that play key roles in SLE immunopathogenesis. (Baker, 2024)
 
2026 Update
Annual policy review completed with a literature search using the MEDLINE database through June 2026. TULIP-SC was a Phase III, multicenter, randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of a subcutaneous administration of anifrolumab versus placebo in participants aged 18 to 70 years with moderate to severe SLE while receiving standard therapy (oral corticosteroids, antimalarial, and/or immunosuppressants).
The primary endpoint was the reduction of disease activity measured using the British Isles Lupus Assessment Group based Composite Lupus Assessment (BICLA) at week 52. The BICLA requires improvement in all organs with disease activity at baseline with no new flares. In the TULIP-SC trial, anifrolumab demonstrated clinically meaningful effects across a range of outcome measures: reduction in SLE disease activity while tapering to low dose of OCS (≤7.5 mg/day), more patients achieving a BICLA response sooner, and numerically delayed time to first flare. In pre-specified secondary and exploratory endpoints, 29.0% of patients taking anifrolumab achieved DORIS remission and 40.1% attained low-level disease activity, as measured by the Low-Level Disease Activity Score (LLDAS).
 
Participants (367) were randomized 1:1 to receive 120mg subcutaneous dose of anifrolumab or placebo administered via a pre-filled, single-use syringe A planned interim analysis was conducted when the first 220 participants reached week 52 or withdrew from the study The trial also includes an open-label extension period of 52 weeks for participants who completed the 52-week treatment period.
CPT/HCPCS:
C9086Injection, anifrolumab-fnia, 1 mg
J0491Injection, anifrolumab-fnia, 1 mg
J3490Unclassified drugs
J3590Unclassified biologics
References:
Aringer M, Costenbader K, Daikh D, et al.(2019) 2019 European League Against Rheumatism/American College of Rheumatology Classification Criteria for Systemic Lupus Erythematosus. Arthritis Rheumatol. 2019;71(9):1400-1412. doi:10.1002/art.40930

Aringer M, Costenbader K, Daikh D, et al.(2019) Guidelines for referral and management of systemic lupus erythematosus in adults. American College of Rheumatology Ad Hoc Committee on Systemic Lupus Erythematosus Guidelines. Annals of the Rheumatic Diseases 2019;78:1151-1159.

Baker T, Sharifian H, Newcombe PJ, et.al.,(2024) Type I interferon blockade with anifrolumab in patients with systemic lupus erythematosus modulates key immunopathological pathways in a gene expression and proteomic analysis of two phase 3 trials. Ann Rheum Dis. 2024 Jul 15;83(8):1018-1027. doi: 10.1136/ard-2023-225445. PMID: 38569851; PMCID: PMC12056589.

Bruce IN, van Vollenhoven RF, Morand EF, et.al.,(2023) Sustained glucocorticoid tapering in the phase 3 trials of anifrolumab: a post hoc analysis of the TULIP-1 and TULIP-2 trials. Rheumatology (Oxford). 2023 Apr 3;62(4):1526-1534. doi: 10.1093/rheumatology/keac491. PMID: 36018235; PMCID: PMC10070065.

Chalhoub, N.E., Wenderfer, S.E., Levy, D.M., et. al.(2022) International Consensus for the Dosing of Corticosteroids in Childhood-Onset Systemic Lupus Erythematosus With Proliferative Lupus Nephritis. Arthritis Rheumatol, 74: 263-273. https://doi.org/10.1002/art.41930

Furie RA, Morand EF, Bruce IN, et al.(2019) Type I interferon inhibitor anifrolumab in active systemic lupus erythematosus (TULIP-1): a randomised, controlled, phase 3 trial. The Lancet Rheumatology, 2019, 1(4), pp. e208-e219. https://doi.org/10.1016/S2665-9913(19)30076-1

Guidelines for referral and management of systemic lupus erythematosus in adults. American College of Rheumatology Ad Hoc Committee on Systemic Lupus Erythematosus Guidelines. Arthritis Rheum. 1999 Sep;42(9):1785-96.

IPD Analytics.(2021) New Drug Review Sapnnelo (anifrolumab-fnia). August 2021

Kalunian KC, Furie R, Morand EF, Bruce IN, Manzi S, Tanaka Y, Winthrop K, Hupka I, Zhang LJ, Werther S, Abreu G, Hultquist M, Tummala R, Lindholm C, Al-Mossawi H.(2023) A Randomized, Placebo-Controlled Phase III Extension Trial of the Long-Term Safety and Tolerability of Anifrolumab in Active Systemic Lupus Erythematosus. Arthritis Rheumatol. 2023 Feb;75(2):253-265. doi: 10.1002/art.42392. Epub 2022 Nov 11. PMID: 36369793.

Kidney Disease: Improving Global Outcomes (KDIGO) Glomerular Diseases Work Group. KDIGO 2021 Clinical Practice Guideline for the Management of Glomerular Diseases. Kidney Int. 2021;100(4S):S1-S276. doi:10.1016/j.kint.2021.05.021

Petri M, Orgai A-M, Alarocón GS, et. al.(2012) Derivation and validation of Systemic Lupus International Collaborating Clinics (SLICC) classification criteria for systemic lupus erythematosus. Arthritis Rheum 2012; 64:2677-2686.

Saphnelo (anifrolumab-fnia). Package insert. AstraZeneca Pharmaceuticals LP, Wilmington, DE; revised 7/2021

SAPHNELO [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP 2023

Saphnelo [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2024.

Saphnelo(2026) package insert Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2026.

The Lancet Rheumatology, 2019, 1(4), pp. e208-e219. https://doi.org/10.1016/S2665-9913(19)30076-1(2020) Trial of Anifrolumab in Active Systemic Lupus Erythematosus. N Engl J Med. 2020;382(3):211-221. doi:10.1056/NEJMoa1912196
Group specific policy will supersede this policy when applicable. This policy does not apply to the Wal-Mart Associates Group Health Plan participants.
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