Immunoglobulin Therapy

Restricted Product(s)

• Alyglo™ intravenous (IV) immune globulin for administration by a healthcare professional
• Asceniv™ intravenous (IV) immune globulin for administration by a healthcare professional
• Bivigam® intravenous (IV) immune globulin for administration by a healthcare professional 
• Flebogamma® intravenous (IV) immune globulin for administration by a healthcare professional
• Gammagard® S/D intravenous (IV) immune globulin for administration by a healthcare professional 
• Gammaplex® intravenous (IV) immune globulin for administration by a healthcare professional 
• *Octagam® intravenous (IV) immune globulin for administration by a healthcare professional 
• Panzyga® intravenous (IV) immune globulin for administration by a healthcare professional 
• *Privigen® intravenous (IV) immune globulin for administration by a healthcare professional 
• Yimmugo® intravenous (IV) immune globulin for administration by a healthcare professional 
• *Gamunex-C® intravenous (IV) or subcutaneous (SC) immune globulin for administration by a healthcare professional 
• *Gammaked™ intravenous (IV) or subcutaneous (SC) immune globulin for administration by a healthcare professional 
• *Gammagard™ Liquid intravenous (IV) or subcutaneous (SC) immune globulin for administration by a healthcare professional 
• **Cutaquig™ subcutaneous (SC) immune globulin for administration by a healthcare professional 
• Cuvitru™ subcutaneous (SC) immune globulin for administration by a healthcare professional 
• **Hizentra® subcutaneous (SC) immune globulin for administration by a healthcare professional 
• **HyQvia™ subcutaneous (SC) immune globulin for administration by a healthcare professional 
• **Xembify™ subcutaneous (SC) immune globulin for administration by a healthcare professional 

*preferred intravenous immune globulin (IVIG) agents
**preferred subcutaneous immune globulin (SCIG) agents

FDA Approved Use

• Alyglo
  • For treatment of primary humoral immunodeficiency (PI) in adults
• Asceniv
  • For treatment of primary humoral immunodeficiency (PI) in adults and adolescents (12 to 17 years of age)
• Bivigam 
  • For treatment of primary humoral immunodeficiency (PI) in patients 2 years of age and older
• Flebogamma
  • For treatment of primary humoral immunodeficiency (PI)
  • For treatment of chronic immune thrombocytopenic purpura (ITP)
• Gammagard S/D
  • For treatment of primary immunodeficiency (PID) in patients 2 years of age and older
  • For prevention of bacterial infections in patients with hypogammaglobulinemia and/or recurrent bacterial infections associated with B-cell chronic lymphocytic leukemia (CLL) 
  • For treatment of chronic idiopathic thrombocytopenic purpura (ITP) 
  • For treatment of Kawasaki syndrome
• Gammaplex
  • For treatment of primary humoral immunodeficiency (PI) in patients 2 years of age and older 
  • For treatment of chronic immune thrombocytopenic purpura (ITP) in adults
• Octagam
  • For treatment of primary immunodeficiencies (PID) 
  • For treatment of chronic immune thrombocytopenic purpura (ITP) in adults 
• Panzyga
  • For treatment of primary humoral immunodeficiency (PI) in patients 2 years of age and older 
  • For treatment of chronic immune thrombocytopenia (ITP) in adults
  • For treatment of chronic inflammatory demyelinating polyneuropathy (CIDP) in adults
• Privigen 
  • For treatment of primary humoral immunodeficiency (PI) 
  • For treatment of chronic immune thrombocytopenic purpura (ITP) in patients 15 years of age and older 
  • For treatment of chronic inflammatory demyelinating polyneuropathy (CIDP) in adults 
    • Limitations of use: Maintenance therapy in CIDP has not been studied beyond 6 months 
• Yimmugo
  • For treatment of primary humoral immunodeficiency (PI) in patients 2 years of age and older
• Gamunex-C
  • For treatment of primary humoral immunodeficiency (PI) in patients 2 years of age and older 
  • For treatment of idiopathic thrombocytopenic purpura (ITP) in adults and children
  • For treatment of chronic inflammatory demyelinating polyneuropathy (CIDP) in adults
    • Limitations of use: Maintenance therapy in CIDP has not been studied beyond 6 months
• Gammaked
  • For treatment of primary humoral immunodeficiency (PI) in patients 2 years of age and older
  • For treatment of idiopathic thrombocytopenic purpura (ITP) in adults and children
  • For treatment of chronic inflammatory demyelinating polyneuropathy (CIDP) in adults
• Gammagard Liquid
  • For replacement treatment of primary humoral immunodeficiency (PI) in patients 2 years of age and older 
  • For maintenance treatment of multifocal motor neuropathy (MMN) in adults, to improve muscle strength and disability 
  • For treatment of chronic inflammatory demyelinating polyneuropathy (CIDP) in adults, to improve neuromuscular disability and impairment
    • Limitations of use:
      • Safety and effectiveness have not been studied in immunoglobulin-naïve patients with CIDP 
      • Maintenance therapy in CIDP has not been studied beyond 6 months 
• Cutaquig
  • For treatment of primary humoral immunodeficiency (PI) in adults and pediatric patients 2 years of age and older
• Cuvitru
  • For treatment of primary humoral immunodeficiency (PI) in patients 2 years of age and older
• Hizentra
  • For treatment of primary immunodeficiency (PI) in patients 2 years of age and older 
  • For maintenance treatment of chronic inflammatory demyelinating polyneuropathy (CIDP) in adults 
• HyQvia
  • For treatment of primary immunodeficiency (PI) in adults and pediatric patients 2 years of age and older
  • For maintenance treatment of chronic inflammatory demyelinating polyneuropathy (CIDP) in adults 
• Xembify
  • For treatment of primary humoral immunodeficiency (PI) in patients 2 years of age and older

Criteria for Medical Necessity

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

Initial Criteria for Approval

Intravenous immunoglobulin (IVIG) may be considered medically necessary when the following criteria are met:

1. The patient has a diagnosis of primary immunodeficiency [medical record documentation required], and the diagnosis has been confirmed by presence of ONE of the following [medical record documentation required]:
   1. Agammaglobulinemia, defined as a total IgG less than 200 mg/dL at baseline prior to immune globulin therapy; OR 
   2. Absence of B lymphocytes; OR
   3. ALL of the following:
      1. ONE of the following:
         1. The patient has selective IgG subclass deficiency, defined as deficiency of 1 or more IgG subclasses (e.g., IgG1, IgG2, IgG3, or IgG4) by at least two standard deviations (SD) below the age-adjusted mean, assessed on 2 separate occasions during infection free period [medical record documentation required]; OR 
         2. The patient has specific antibody deficiency (SAD) with normal levels of both immunoglobulin and total IgG subclasses [medical record documentation required]; OR 
         3. The patient has persistent hypogammaglobulinemia, defined as total IgG level less than 400 mg/dL or below the lower limit of normal (i.e., at least two SD below the age-adjusted mean) at baseline prior to immune globulin therapy [medical record documentation required]; OR
         4. The patient has another primary immunodeficiency (e.g., congenital agammaglobulinemia, hypogammaglobulinemia, common variable immunodeficiency, severe combined immunodeficiency, Wiskott-Aldrich syndrome, X-linked agammaglobulinemia, X-linked hyperimmunoglobulinemia M syndrome, ataxia telangiectasia) [medical record documentation required]; AND
      2. The patient has a lack of response or inability to mount an adequate antibody response to protein and/or polysaccharide antigens (e.g., inability to make IgG antibody against either diphtheria and tetanus toxoids, or pneumococcal polysaccharide vaccine, or both) [medical record documentation required]; AND
      3. The patient has evidence of recurrent, persistent, severe, difficult-to-treat infections despite aggressive prophylactic management and treatment with antibiotics [medical record documentation required]; OR
2. The requested agent will be used for the prevention of bacterial infection in HIV-infected children [medical record documentation required]; AND
   1. The patient is less than 13 years old; AND
   2. The patient has hypogammaglobulinemia, defined as total IgG level less than 400 mg/dL or below the lower limit of normal (i.e., at least two standard deviations below the age-adjusted mean) at baseline prior to immune globulin therapy [medical record documentation required]; OR
3. The patient has a diagnosis of human parvovirus B19-associated severe anemia [medical record documentation required]; OR
4. The patient has a diagnosis of toxic shock syndrome [medical record documentation required]; OR
5. The patient has a diagnosis of chronic lymphocytic leukemia (CLL) [medical record documentation required]; AND
   1. The patient has hypogammaglobulinemia, defined as total IgG level less than 400 mg/dL or below the lower limit of normal (i.e., at least two standard deviations below the age-adjusted mean) at baseline prior to immune globulin therapy [medical record documentation required]; AND
   2. The patient has a history of recurrent, persistent bacterial infections requiring antibiotics and/or hospitalization [medical record documentation required]; OR 
6. The patient has a diagnosis of multiple myeloma [medical record documentation required]; AND
   1. The patient has a history of recurrent, persistent, life-threatening bacterial infections requiring antibiotics and/or hospitalization [medical record documentation required]; OR
7. The patient has another B-cell lymphoproliferative disease, including acute lymphoblastic leukemia (ALL) and/or B-cell lymphomas [medical record documentation required]; AND
   1. The patient has treatment-related hypogammaglobulinemia, defined as total IgG level less than 400 mg/dL or below the lower limit of normal (i.e., at least two standard deviations below the age-adjusted mean) at baseline prior to immune globulin therapy [medical record documentation required]; OR
8. The patient has a diagnosis of a severe, progressive autoimmune mucocutaneous blistering disease, including pemphigus, pemphigoid, pemphigus vulgaris, pemphigus foliaceus [medical record documentation required]; AND
   1. The patient has tried and had an inadequate response to conventional therapy (e.g., corticosteroids, azathioprine, cyclophosphamide) for treatment of this indication [medical record documentation required]; OR
   2. The patient has an intolerance, FDA labeled contraindication, or hypersensitivity to ALL conventional therapy used in the treatment of autoimmune mucocutaneous blistering diseases [medical record documentation required]; OR
9. The patient has a diagnosis of acute, severe idiopathic thrombocytopenic purpura (ITP) [medical record documentation required]; AND
   1. The patient has acute disease with presence of ONE of the following [medical record documentation required]:
      1. Major bleeding (e.g., life-threatening bleeding and/or clinically important mucocutaneous bleeding); OR 
      2. Severe thrombocytopenia and at high risk for bleeding complications; OR 
      3. Severe thrombocytopenia and a slow or inadequate response to corticosteroids; OR 
      4. Severe thrombocytopenia and a predictable risk of bleeding in the future (e.g., a procedure or surgery with a high bleeding risk); AND
   2. The patient has presence of symptoms associated with ITP [medical record documentation required]; AND
   3. The patient has persistent thrombocytopenia (i.e., platelets < 20,000/µL [adult] or 30,000/µL [child]) despite treatment with corticosteroids and splenectomy [medical record documentation required]; OR
   4. The patient has an intolerance, FDA labeled contraindication, or hypersensitivity to corticosteroids used for the treatment of ITP [medical record documentation required]; OR
10. The patient has a diagnosis of chronic idiopathic thrombocytopenia purpura [medical record documentation required]; AND
    1. The patient has disease duration of at least 6 months [medical record documentation required]; AND
    2. The patient has presence of symptoms associated with ITP [medical record documentation required]; AND
    3. The patient has persistent thrombocytopenia (i.e., platelets < 20,000/µL [adult] or < 30,000/µL [child]) despite treatment with corticosteroids and splenectomy [medical record documentation required]; OR
    4. The patient has an intolerance, FDA labeled contraindication, or hypersensitivity to corticosteroids used for the treatment of ITP [medical record documentation required]; OR
11. The patient has a diagnosis of Guillain-Barre syndrome [medical record documentation required]; AND
    1. The requested agent will be used as an equivalent alternative to plasma exchange [medical record documentation required]; OR
12. The patient has a diagnosis of Kawasaki syndrome [medical record documentation required]; OR
13. The patient has a diagnosis of granulomatosis with polyangiitis (also known as Wegener granulomatosis) [medical record documentation required]; OR
14. The patient has a diagnosis of chronic inflammatory demyelinating polyneuropathy (CIDP) [medical record documentation required]; AND
    1. The patient has progressive symptoms present for at least 2 months [medical record documentation required]; AND
    2. The patient has progressive or relapsing motor sensory impairment of more than one limb [medical record documentation required]; AND
    3. The patient has electrodiagnostic findings indicating at least ONE of the following are present [medical record documentation required]:
       1. Motor distal latency prolongation in 2 nerves; OR 
       2. Reduction of motor conduction velocity in 2 nerves; OR 
       3. Prolongation of F-wave latency in 2 nerves; OR
       4. Absence of F-waves in at least 1 nerve; OR
       5. Partial motor conduction block of at least 1 motor nerve; OR
       6. Abnormal temporal dispersion in at least 2 nerves; OR 
       7. Distal CMAP duration increase in at least 1 nerve; OR 
15. The patient has a diagnosis of multifocal motor neuropathy [medical record documentation required]; AND
    1. The diagnosis has been confirmed by ALL of the following [medical record documentation required]:
       1. Weakness with slowly progressive or stepwise progressive course over at least 1 month; AND 
       2. Asymmetric involvement of two or more nerves; AND 
       3. Absence of motor neuron signs and bulbar signs; OR
16. The patient has a diagnosis of Eaton-Lambert myasthenic syndrome [medical record documentation required]; AND
    1. The patient has tried and had an inadequate response to an anticholinesterase agent and/or corticosteroid [medical record documentation required]; OR
    2. The patient has an intolerance, FDA labeled contraindication, or hypersensitivity to ALL anticholinesterase agents and corticosteroids used in the treatment of Eaton-Lambert myasthenic syndrome [medical record documentation required]; OR
17. The patient has a diagnosis of neuromyelitis optica [medical record documentation required]; AND
    1. The patient has a contraindication or lack of response to first-line treatment [medical record documentation required]; AND
    2. The requested agent will be used as an alternative treatment; OR
18. The patient has a diagnosis of severe, refractory myasthenia gravis [medical record documentation required]; AND
    1. The patient has chronic debilitating disease despite treatment with cholinesterase inhibitors [medical record documentation required]; OR
    2. The patient has experienced complications from or trial and failure of corticosteroids and/or azathioprine [medical record documentation required]; OR
19. The requested agent will be used for treatment of a myasthenic exacerbation (i.e., an acute episode of respiratory muscle weakness) [medical record documentation required]; AND
    1. The patient has a contraindication to treatment with plasma exchange [medical record documentation required]; OR
20. The patient has a diagnosis of dermatomyositis or polymyositis [medical record documentation required]; AND
    1. The patient’s disease is refractory to treatment with corticosteroids [medical record documentation required]; AND
    2. The patient will be using the requested agent in combination with other immunosuppressive agents; OR 
21. The patient has a diagnosis of warm antibody hemolytic anemia [medical record documentation required]; AND
    1. The patient is refractory to prednisone AND splenectomy [medical record documentation required]; OR
22. The patient has a diagnosis of antiphospholipid syndrome [medical record documentation required]; OR
23. The patient has a diagnosis of autoimmune encephalitis (AE), including but not limited to antibody-mediated AE [medical record documentation required]; AND
    1. The patient has tried and had an inadequate response to a glucocorticoid [medical record documentation required]; OR 
    2. The patient has an intolerance, FDA labeled contraindication, or hypersensitivity to all glucocorticoids [medical record documentation required]; OR
24. The patient has a diagnosis of neonatal alloimmune thrombocytopenia [medical record documentation required]; OR
25. The patient has a diagnosis of hemolytic disease of the fetus and newborn (i.e., erythroblastosis fetalis) [medical record documentation required]; OR 
26. The requested agent will be used in the transplant setting for one of the following circumstances:
    1. The patient is a recipient of a hematopoietic cell transplantation [medical record documentation required]; AND
       1. The patient is at least 180 days post-transplantation; AND
       2. The patient has a total IgG level less than 400 mg/dL [medical record documentation required]; AND
       3. The requested agent will be used for prevention of infection (NOTE: For IVIG requests within 180 days post-transplantation date, please refer to internal protocol found within Blue Cross NC Clinical Transplant Process Guidelines); OR
    2. Prior to solid organ transplant as treatment for patients at high risk of antibody-mediated rejection including highly allo-sensitized patients and those receiving an ABO incompatible organ [medical record documentation required]; OR
    3. For the treatment of solid organ transplant antibody-mediated rejection [medical record documentation required]; OR
27. The patient has a diagnosis of stiff person syndrome [medical record documentation required]; AND
    1. The patient is not controlled by other therapies used in the treatment of stiff person syndrome [medical record documentation required]; OR
28. The patient has another diagnosis that is an FDA approved indication for the requested agent [medical record documentation required]; OR
29. The patient has another diagnosis that is an indication supported by compendia (AHFS, NCCN 1 or 2a recommended indication, or DrugDex level of evidence 1 or 2A) for the requested agent [medical record documentation required]; AND
30. The patient does NOT have selective immunoglobulin A (IgA) deficiency with known antibody against IgA; AND
31. The requested agent will NOT be used to treat relapsing-remitting multiple sclerosis; AND
32. The patient does NOT have any FDA labeled contraindications to the requested agent; AND
33. If the requested agent is a non-preferred intravenous immune globulin (IVIG) (e.g., Alyglo, Asceniv, Bivigam, Flebogamma, Gammaplex, Gammagard S/D, Panzyga, Yimmugo), ONE of the following:
    1. The patient is currently being treated with the requested agent and has been stable on therapy for at least 180 days; OR
    2. The patient has been treated with the requested agent within the past 180 days AND is at risk if therapy is changed; OR
    3. The patient has tried and had an inadequate response to TWO preferred IVIG agents (i.e., Octagam, Gamunex-C, Gammaked, Gammagard, Privigen) [medical record documentation required]; OR
    4. The patient has an intolerance or hypersensitivity to TWO preferred IVIG agents (i.e., Octagam, Gamunex-C, Gammaked, Gammagard, Privigen) that is NOT expected to occur with the requested agent [medical record documentation required]; OR
    5. The patient has an FDA labeled contraindication to ALL preferred IVIG agents (i.e., Octagam, Gamunex-C, Gammaked, Gammagard, Privigen) that is NOT expected to occur with the requested agent [medical record documentation required]; OR
    6. The prescriber has provided documentation in support of the use of the non-preferred IVIG agent over TWO preferred IVIG agents (i.e., Octagam, Gamunex-C, Gammaked, Gammagard, Privigen) for the requested indication [medical record documentation required]; AND 
34. The requested quantity does NOT exceed the maximum units allowed for the duration of approval (see table below); AND
35. 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)*

Subcutaneous immunoglobulin (SCIG) may be considered medically necessary when the following criteria are met:

1. The patient has a diagnosis of primary immunodeficiency [medical record documentation required], and the diagnosis has been confirmed by presence of ONE of the following [medical record documentation required]:
   1. Agammaglobulinemia, defined as a total IgG less than 200 mg/dL at baseline prior to immune globulin therapy; OR
   2. Absence of B lymphocytes; OR
   3. ALL of the following: 
      1. ONE of the following
         1. The patient has selective IgG subclass deficiency, defined as deficiency of 1 or more IgG subclasses (e.g., IgG1, IgG2, IgG3, or IgG4) by at least two standard deviations (SD) below the age-adjusted mean, assessed on 2 separate occasions during infection free period [medical record documentation required]; OR
         2. The patient has specific antibody deficiency (SAD) with normal levels of both immunoglobulin and total IgG subclasses [medical record documentation required]; OR
         3. The patient has persistent hypogammaglobulinemia, defined as total IgG level less than 400 mg/dL or below the lower limit of normal (i.e., at least two SD below the age-adjusted mean) at baseline prior to immune globulin therapy [medical record documentation required]; OR
         4. The patient has another primary immunodeficiency (e.g., congenital agammaglobulinemia, hypogammaglobulinemia, common variable immunodeficiency, severe combined immunodeficiency, Wiskott-Aldrich syndrome, X-linked agammaglobulinemia, X-linked hyperimmunoglobulinemia M syndrome, ataxia telangiectasia) [medical record documentation required]; AND
      2. The patient has a lack of response or inability to mount an adequate antibody response to protein and/or polysaccharide antigens (e.g., inability to make IgG antibody against either diphtheria and tetanus toxoids, or pneumococcal polysaccharide vaccine, or both) [medical record documentation required]; AND
      3. The patient has evidence of recurrent, persistent, severe, difficult-to-treat infections despite aggressive prophylactic management and treatment with antibiotics [medical record documentation required]; OR
2. The patient has another diagnosis that is an FDA approved indication for the requested agent [medical record documentation required]; OR
3. The patient has another diagnosis that is an indication supported by compendia (AHFS, NCCN 1 or 2a recommended indication, or DrugDex level of evidence 1 or 2A) for the requested agent [medical record documentation required]; AND
4. The requested agent will NOT be used to treat relapsing-remitting multiple sclerosis; AND 
5. The patient does NOT have selective immunoglobulin A (IgA) deficiency with known antibody against IgA; AND
6. The patient does NOT have any FDA labeled contraindications to the requested agent; AND
7. ONE of the following:
   1. The patient is currently being treated with the requested agent and has been stable on therapy for at least 180 days; OR
   2. The patient has been treated with the requested agent within the past 180 days AND is at risk if therapy is changed; OR
   3. The patient has tried and had an inadequate response to a preferred intravenous immune globulin (IVIG) agent (i.e., Octagam, Gamunex-C, Gammaked, Gammagard, Privigen) [medical record documentation required]; OR
   4. The patient has an intolerance or hypersensitivity to a preferred IVIG agent (i.e., Octagam, Gamunex-C, Gammaked, Gammagard, Privigen) that is NOT expected to occur with the requested agent [medical record documentation required]; OR
   5. The patient has an FDA labeled contraindication to ALL preferred IVIG agents (i.e., Octagam, Gamunex-C, Gammaked, Gammagard, Privigen) that is NOT expected to occur with the requested agent [medical record documentation required]; OR
   6. The prescriber has provided documentation in support of the use of the requested SCIG agent over a preferred IVIG agent (i.e., Octagam, Gamunex-C, Gammaked, Gammagard, Privigen) for the requested indication [medical record documentation required]; AND 
8. If the requested agent is a non-preferred subcutaneous immune globulin (SCIG) (e.g., Cuvitru), ONE of the following:
   1. The patient is currently being treated with the requested agent and has been stable on therapy for at least 180 days; OR
   2. The patient has been treated with the requested agent within the past 180 days AND is at risk if therapy is changed; OR
   3. The patient has tried and had an inadequate response to TWO preferred SCIG agents (i.e., Cutaquig, Hizentra, HyQvia, Xembify) [medical record documentation required]; OR
   4. The patient has an intolerance or hypersensitivity to TWO preferred SCIG agents (i.e., Cutaquig, Hizentra, HyQvia, Xembify that is NOT expected to occur with the requested agent [medical record documentation required]; OR
   5. The patient has an FDA labeled contraindication to ALL preferred SCIG agents (i.e., Cutaquig, Hizentra, HyQvia, Xembify) that is NOT expected to occur with the requested agent [medical record documentation required]; OR
   6. The prescriber has provided documentation in support of the use of the non-preferred SCIG agent over TWO preferred SCIG agents (i.e., Cutaquig, Hizentra, HyQvia, Xembify) for the requested indication [medical record documentation required]; AND
9. The requested quantity does NOT exceed the maximum units allowed for the duration of approval (see table below); AND
10. 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:
Asceniv for all indications: 180 days (6 months)
All other IVIG and SCIG products: 365 days (1 year)

**NOTE: For hematopoietic cell transplantation: for IVIG requests within 180 days post-transplantation date, please refer to internal protocol found within Blue Cross NC Clinical Transplant Process Guidelines. 

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. ONE of the following:
   1. The patient was previously approved for short term use of the requested agent (i.e., 6 months) AND the prescriber has provided documentation supporting continued use of the requested agent [medical record documentation required]; OR
   2. The patient was previously approved for more than 6 months AND ONE of the following:
      1. The patient has had clinical improvement or disease stabilization (e.g., IgG level has improved from pre-treatment levels with the requested agent, reduction in the number and/or severity of difficult to treat infections, reduction in seizure frequency); OR
      2. The prescriber has provided documentation supporting continued use of the requested agent [medical record documentation required]; AND
4. The requested agent will NOT be used to treat relapsing-remitting multiple sclerosis; AND
5. The patient does NOT have selective immunoglobulin A (IgA) deficiency with known antibody against IgA; AND
6. The patient does NOT have any FDA labeled contraindications to the requested agent; AND
7. The requested quantity does NOT exceed the maximum units allowed for the duration of approval (see table below); AND
8. 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:
Asceniv for all indications: 180 days (6 months)
All other IVIG and SCIG products: 365 days (1 year)

**NOTE: For hematopoietic cell transplantation: for IVIG requests within 180 days post-transplantation date, please refer to internal protocol found within Blue Cross NC Clinical Transplant Process Guidelines. 

*Site of Care Medical Necessity Criteria

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.

References

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

1. Dalmau J, Graus F. Antibody-mediated encephalitis. N Engl J Med. 2018;378(9):840-851.
2. European Federation of Neurological Societies/Peripheral Nerve Society Guideline on management of chronic inflammatory demyelinating polyradiculoneuropathy: report of a joint task force of the European Federation of Neurological Societies and the Peripheral Nerve Society – First Revision. Eur J Neurol. 2010;17(3):356-63.
3. Gastaldi M, Thouin A, Vincent A. Antibody-mediated autoimmune encephalopathies and immunotherapies. Neurotherapeutics. 2016;13(1):147-62.
4. Orange JS, Hossny EM, Weiler CR, et al. Use of intravenous immunoglobulin in human disease: a review of evidence by members of the Primary Immunodeficiency Committee of the American Academy of Allergy, Asthma and Immunology. J Allergy Clin Immunol 2006;117:S525-S553.

Policy Implementation/Update Information

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.

January 2025: Coding change: For Alyglo, added HCPCS code J1552 to dosing reference table effective 1/1/2025; deleted C9399, J3490, and J3590 termed 12/31/2024. Adjusted the following codes within the dosing table for clarity: Added 90283 to Alyglo, added 90283 to Yimmugo, and removed J1599 from Panzyga.

January 2025: Criteria change: For subcutaneous immunoglobulin (SCIG) products: Adjusted preferred SCIG product options to add Cutaquig and HyQvia to existing preferred Hizentra and Xembify. Updated SCIG trial and failure criteria to require use of two preferred SCIG agents prior to use of a non-preferred SCIG agent (e.g., Cuvitru) unless other criteria are met. Consolidated SCIG trial and failure criteria for required use of a preferred IVIG agent prior to use of a SCIG agent unless other criteria are met, for clarity with no change to policy intent.

September 2024: Criteria update: Added new to market product Yimmugo (intravenous immune globulin) for treatment of primary humoral immunodeficiency (PI) in patients 2 years of age and older, with corresponding criteria as a non-preferred IVIG product with requirement of trial and failure of two preferred IVIG products; added associated dosing table updates and HCPCS codes C9399, J3490, and J3590. Other minor updates made throughout policy for clarity with no change to policy intent.

February 2024: Criteria update: For Gammagard Liquid, added newly approved indication for treatment of chronic inflammatory demyelinating polyneuropathy (CIDP) in adults per update to FDA label and added associated dosing table updates.

February 2024: Criteria change: Added new to market product Alyglo (intravenous immune globulin) for treatment of primary humoral immunodeficiency (PI) in adults, with corresponding criteria as a non-preferred IVIG product with requirement of trial and failure of two preferred IVIG products; added associated dosing table updates and HCPCS codes C9399, J3490, and J3590. For Bivigam, expanded indication to patients 2 years of age and older per update to FDA label. For HyQvia, added indication for maintenance therapy in adults with chronic inflammatory demyelinating polyneuropathy (CIDP) per update to FDA label, expanded PI indication to patients 2 years of age and older per FDA label, and made other minor updates throughout policy according to FDA label for clarity.

July 2023: Coding change: Added HCPCS code J1576 for Panzyga effective 7/1/2023. Removed J1599 from Asceniv, Bivigam, Flebogamma, Gammaked, Gammaplex, Gamunex-C, Octagam, and Privigen for clarity according to coding definition. Removed Carimune NF from policy due to product discontinuation.

October 2022: Coding update: In dosing reference table, removed HCPCS codes J1599 and J1569 for Gammagard SD and removed J1599 from Gammagard Liquid

October 2022: Criteria change: Added requirement of trial and failure of an IVIG product prior to use of a SCIG product unless other criteria are met. Added requirement of trial and failure of two preferred IVIG products prior to use of non-preferred IVIG products unless other criteria are met. Added requirement of trial and failure of Hizentra and Xembify prior to use of non-preferred SCIG products (Cutaquig, Cuvitru), and trial and failure of one preferred IVIG product prior to use of HyQvia unless other criteria are met. Added continuation criteria. Policy notification given 8/4/2022 for effective date 10/1/2022.

July 2022: Coding update: Added HCPCS code J1551 to dosing reference table for Cutaquig effective 7/1/2022, deleted C9399, J3490, and J3590 termed 6/30/2022.

April 2022: Criteria change: Added requirement of trial and failure of two preferred IVIG and/or SCIG products prior to use of non-preferred Asceniv unless other criteria are met. Adjusted duration of approval for Asceniv to 6 months for all indications. Policy notification given 2/3/2022 for effective date 4/4/2022.

February 2022: Criteria update: Expanded indication for Cutaquig to patients 2 years of age and older per FDA approval update.

June 2021: Criteria change: Added selective IgG subclass deficiency and specific antibody deficiency (SAD) under primary immunodeficiencies for IVIg and SCIg; added age requirement for bacterial infection prevention in HIV-infected children; added requirements for FDA labeled or compendia accepted indication with specific evidence level rating, no FDA labeled contraindications, and maximum units; medical policy formatting change. Policy notification given 4/16/2021 for effective date 6/16/2021.

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