Notification



Notification Issue Date:



Medical Policy Bulletin


Title:Immune Globulin Intravenous (IVIG), Subcutaneous (SCIG)

Policy #:08.00.13v

This policy is applicable to the Company’s commercial products only. Policies that are applicable to the Company’s Medicare Advantage products are accessible via a separate Medicare Advantage policy database.


The Company makes decisions on coverage based on Policy Bulletins, benefit plan documents, and the member’s medical history and condition. Benefits may vary based on contract, and individual member benefits must be verified. The Company determines medical necessity only if the benefit exists and no contract exclusions are applicable.

When services can be administered in various settings, the Company reserves the right to reimburse only those services that are furnished in the most appropriate and cost-effective setting that is appropriate to the member’s medical needs and condition. This decision is based on the member’s current medical condition and any required monitoring or additional services that may coincide with the delivery of this service.

This Medical Policy Bulletin document describes the status of medical technology at the time the document was developed. Since that time, new technology may have emerged or new medical literature may have been published. This Medical Policy Bulletin will be reviewed regularly and be updated as scientific and medical literature becomes available. For more information on how Medical Policy Bulletins are developed, go to the About This Site section of this Medical Policy Web site.



Policy

Coverage is subject to the terms, conditions, and limitations of the member's contract.

When services can be administered in various settings, the Company reserves the right to reimburse only those services that are furnished in the most appropriate and cost-effective setting that is appropriate to the member’s medical needs and condition. This decision is based on the member’s current medical condition and any required monitoring or additional services that may coincide with the delivery of this service.

MEDICALLY NECESSARY

SUBCUTANEOUS IMMUNE GLOBULIN (SCIG)
Company-Designated Preferred Products For Primary Immunodeficiency Disorders (PIDD)

Cutaquig, Cuvitru, Hizentra®, HyQvia, and Xembify are brand names of subcutaneous immune globulin (SCIG) products that are currently on the market. There are also certain intravenous immune globulin (IVIG) products (e.g., Gammagard Liquid®, Gammaked®, Gamunex-C®) that can be administered intravenously or subcutaneously for primary immunodeficiency disorders (PIDD). Although there are several brands of IVIG and SCIG on the market approved for the treatment of PIDD, there is no reliable evidence of the superiority of any one brand compared to others. The Company has designated Gammagard Liquid®, Gammaked®, and Gamunex-C® as its preferred subcutaneous products. These products are less costly and at least as likely to produce equivalent therapeutic results as the non-preferred products, which include, but are not limited to: Cutaquig, Cuvitru, Hizentra®, HyQvia, and Xembify.

Subcutaneous immune globulin (SCIG) (e.g., Cutaquig, Cuvitru, Hizentra®, HyQvia, and Xembify) products are considered medically necessary and, therefore, covered for the following indications when the dosing and frequency requirements listed in Attachment A and the following criterion is met:
  • The individual has had a documented failure, contraindication* or intolerance to the subcutaneous administration of The Company's preferred subcutaneous products (i.e., Gammagard Liquid®, Gammaked®, or Gamunex-C®)

* Contraindications to IG products may include factors such as, but not limited to: volume load, sugar content, sodium content, osmolality, IgA content, or pH.

Immunodeficiency Syndromes
  • Hyperimmunoglobulinemia E syndrome (HIES) (Hyper-IgE syndromes, Job’s syndrome) when all of the following signs and symptoms are present:
    • Individual has eosinophilia (500 or more eosinophils/microL)
    • Individual has elevated serum IgE (>2000 IU/ml), with normal IgG, IgA, and IgM levels
    • Individual has eczema, recurrent staphylococcal lung infections, and/or skin abscesses documented in office or hospital charts
    • Individual has had a documented failure, contraindication* or intolerance to the subcutaneous administration of The Company's preferred subcutaneous products (i.e., Gammagard Liquid®, Gammaked®, or Gamunex-C®) (See "Company-Designated Preferred Products For Primary Immunodeficiency Disorders (PIDD)" section above and "NOT MEDICALLY NECESSARY USES FOR SCIG" section below).
  • Primary immunodeficiency disorders (PIDD) when the individual has a confirmed genetic diagnosis or laboratory evidence of PIDD or the individual meets both of the following criteria:
    • Individual has a personal history of recurrent, antibiotic-refractory, bacterial infections of the ear (e.g., otitis media) or sinopulmonary infections (e.g., sinusitis, bronchitis/bronchiectasis, pneumonia), which are documented in office or hospital charts.
    • Individual has a deficiency of antibody response to at least one of the following antigens (e.g., proteins, polysaccharides, or viral antigens)
      • Polyvalent pneumococcal polysaccharide vaccine (e.g., Pneumovax 23), measured at the time of immunization and 4-8 weeks after vaccination.
        • A protective (normal) response to each pneumococcal serotype is defined as a titer equal to or greater than 1.3 mcg/mL antibody.
            1. For individuals ages 6 to 65 years, a normal response is defined as conversion of 70% of the serotypes tested with at least a 2-fold increase in the titers.
            2. For children 24 months through 5 years of age, a normal response is defined as the conversion of 50% or more of the serotypes tested with at least a 2-fold increase in the titers.
            3. (Note: When reported, the conversion factor for nanograms of antibody nitrogen per milliliter (ng N/mL) to antibody micrograms per milliliter is as follows: 160ng N/mL = 1 mcg/mL)
      • Protein antigens, tetanus/diphtheria vaccine measured at the time of immunization and 3 to 4 weeks after vaccination:
        • A protective (normal) response is defined as any of the following:
            1. At least a 4-fold increase for protein antigens
            2. A serum diphtheria antitoxin level of 0.01 International Units (IU)/mL is the lowest level giving some degree of protection, and levels of at least 0.1 IU/mL are generally regarded as protective
            3. A protective level for Tetanus is 0.15 IU/mL
    • Individual has had a documented failure, contraindication* or intolerance to the subcutaneous administration of The Company's preferred subcutaneous products (i.e., Gammagard Liquid®, Gammaked®, or Gamunex-C®) (See "Company-Designated Preferred Products For Primary Immunodeficiency Disorders (PIDD)" section above and "NOT MEDICALLY NECESSARY USES FOR SCIG" section below).
    The list of PIDDs includes, but is not limited to:
      1. Ataxia-telangectasia
      2. Autosomal recessive agammaglobulinemia
      3. Caspase 8 deficiency
      4. Common variable immunodeficiency (including TACI and ICOS mutation)
      5. DiGeorge syndrome
      6. DOCK (dedicator of cytokinesis 8) deficiency
      7. Griscelli syndrome
      8. Hypogammaglobulinemia, persistent (IgG less than or equal to 400 mg/dL or less than two standard deviations from normal)
      9. IgG-subclass deficiency (deficiency of one or more IgG subclasses to levels less than 2 standard deviations below the age-specific mean, in the presence of normal or near-normal total IgG levels. These levels must be assessed on at least two occasions while the individual is free of acute infections).
      10. NEMO (mutations in IKK-gamma) deficiency
      11. Nijmegen breakage syndrome
      12. Purine nucleoside phosphorylase [PNP] deficiency
      13. Selective IgA deficiency with IgG subclass deficiency (reduced serum IgA levels [less than 7mg/dL] and normal IgG and IgM levels)
      14. Severe combined immunodeficiency (SCID)
      15. Specific antibody deficiency (Selective antibody deficiency) with normal immunoglobulins
        1. Individual has impaired production of specific antibodies to polysaccharide antigens after vaccination and normal responses to protein antigens
      16. Transient hypogammaglobulinemia of infancy
      17. WHIM (warts, hypogammaglobulinemia, immunodeficiency, and myelokathexis) syndrome
      18. Wiskott-Aldrich syndrome
      19. X-linked agammaglobulinemia (aka, Bruton's agammaglobulinemia, congenital agammaglobulinemia)
      20. X-linked and autosomal recessive hyper IgM syndromes
      21. X-linked immunodeficiency
      22. X-linked lymphoproliferative disease

Neurological and Musculoskeletal Disorders
  • Chronic inflammatory demyelinating polyneuropathies (CIDP)
    • Individual will begin treatment with SCIG after transitioning from IVIG.
    • There must be objective clinical evidence to support the diagnosis of CIDP (such as impaired function measured by a standard clinical scale at the time of initial therapy [e.g., slowing of nerve conduction velocity on electromyography, nerve conduction studies]).
    • Individual has had a documented failure, contraindication* or intolerance to the subcutaneous administration of The Company's preferred subcutaneous products (i.e., Gammagard Liquid®, Gammaked®, or Gamunex-C®) (See "Company-Designated Preferred Products For Primary Immunodeficiency Disorders (PIDD)" section above and "NOT MEDICALLY NECESSARY USES FOR SCIG" section below).

INTRAVENOUS IMMUNE GLOBULIN (IVIG)
Use of intravenous immune globulin (IVIG) therapy (e.g., AscenivTM, Bivigam®, Carimune NF®, Flebogamma®, Gammagard Liquid®, Gammagard S/D®, Gammaked®, Gammaplex®, Gamunex-C®, Octagam®, Panzyga®, Privigen®) is considered medically necessary and, therefore, covered for the following indications when the dosing and frequency requirements listed in Attachment A and the following criteria are met:

Dermatologic
  • Autoimmune mucocutaneous blistering disease for the following biopsy-proven conditions: pemphigus vulgaris, pemphigus foliaceous, bullous pemphigoid, mucous membrane pemphigoid (cicatricial pemphigoid), benign mucous membrane pemphigoid, with or without mention of ocular movement, epidermolysis bullosa acquisita when one of the following criteria is met:
    • The individual failed conventional therapy (e.g., steroids, methotrexate, immunosuppressive therapy) or conventional therapy is contraindicated.
    • The individual has a rapidly progressive disease in which a clinical response could not be effected quickly enough using conventional agents. In this case, IVIG is given along with conventional treatments, and IVIG would be used only until conventional therapy could take effect.

IVIG for the treatment of autoimmune mucocutaneous blistering disease must be used for short-term therapy, not maintenance therapy.
  • Erythema multiforme major (Stevens-Johnson syndrome and toxic epidermal necrolysis)
  • Scleromyxedema

Hematologic
  • Acute idiopathic thrombocytopenic purpura (ITP) when one of the following criteria is met:
    • The individual requires a rapid platelet count increase (e.g., prior to surgical procedures, to control excessive bleeding, to defer or avoid a splenectomy).
    • The individual has acute bleeding due to severe thrombocytopenia (platelet counts usually less than 30,000/mm3).
    • The individual has severe thrombocytopenia (platelet counts less than 20,000/mm3) and is considered at risk for intracerebral hemorrhage.
  • Anemia, autoimmune hemolytic (AIHA) when the following criterion is met:
    • The individual has had prior treatment with corticosteroids and/or splenectomy, unless contraindicated.
  • Anemia due to parvovirus B19 infection:
    • In individuals with chronic parvovirus B19 infection and severe anemia associated with bone marrow suppression
  • Chronic refractory idiopathic thrombocytopenic purpura (ITP) when all of the following criteria are met:
    • The individual has a disease duration of greater than 6 months.
    • The individual has no concurrent illness or disease to explain the thrombocytopenia.
    • The individual has platelet counts that remain persistently at or below 20,000/mm3.
    • The individual has had splenectomy and/or prior treatment with corticosteroids, unless documented failure, contraindication, or intolerance to corticosteroids exists.
  • Idiopathic thrombocytopenic purpura (ITP) during pregnancy when one of the following criteria is met:
    • The individual has previously delivered infants with autoimmune thrombocytopenia.
    • The individual's platelet counts are less than 50,000/mm3 during the current pregnancy.
    • The individual has a history of splenectomy.
  • Fetal/neonatal alloimmune thrombocytopenia
  • Rh and ABO incompatibility (moderate to severe) as treatment in addition to phototherapy to prevent or delay exchange transfusion in neonates
  • Systemic Capillary Leak Syndrome (SCLS) or Clarkson's Disease when associated with monoclonal gammopathy

Immunodeficiency Syndromes, Primary and Secondary
  • Acquired (secondary) hypogammaglobulinemia in oncologic conditions:
    • Chimeric antigen receptor (CAR) T cell therapy (e.g., tisagenlecleucel [Kymriah™], axicabtagene ciloleucel [Yescarta™]) acquired hypogammaglobulinemia when the individual has an IgG level of less than 600 mg/dL.
    • Chronic lymphocytic leukemia with associated hypogammaglobulinemia when one of the following criteria is met:
      • The individual has an IgG level of less than 600 mg/dL.
      • The individual presents evidence of a specific antibody deficiency.
      • The individual presents with serious, recurrent bacterial infections.
    • Multiple myeloma with associated hypogammaglobulinemia in an individual who has a high risk of recurrent infections despite prophylactic antibiotic therapy
    • Other malignant diseases with associated hypogammaglobulinemia in an individual who has a high risk of serious, recurrent bacterial infections
  • Acquired von Willebrand disease associated with IgG-MGUS (monoclonal gammopathy of undetermined significance of the IgG Class) or antibody-mediated acquired von Willebrand disease in individuals in life-threatening situations or prior to surgery when treatment of the underlying condition is not possible.
    • Documented failure, contraindication, or intolerance to standard treatment (e.g., desmopressin and von Willebrand factor replacement)
  • Antineutrophil cytoplasmic antibodies (ANCA)--associated vasculitides (Wegener's Granulomatosis, Microscopic Polyangiitis [MPA], Churg-Strauss syndrome):
    • The individual is unresponsive/refractory to, intolerant of, or has a contraindication to other standard therapies (e.g., corticosteroids, immunosuppressants)
  • Autoimmune neutropenia
  • Bone marrow transplantation when both of the following criteria are met:
    • The individual is 20 years of age or older and has had a transplant for a covered indication.
    • The individual received the transplant within the past 90 days.
  • Catastrophic antiphospholipid syndrome (CAPS) when all of the following criteria are met:
    • The condition is life-threatening.
    • The individual has severe thrombocytopenia and features of microangiopathy (e.g., thrombocytopenia, microangiopathic hemolytic anemia).
    • The individual is unresponsive/refractory to, intolerant of, or has a contraindication to other standard therapies (i.e., corticosteroids and anticoagulants).
    • IVIG must be used in combination with plasma exchange.
  • Coagulopathy due to acquired inhibitor of clotting factor VIII
  • Hematopoietic stem cell transplant (HSCT) for an adult, adolescent, or pediatric allogeneic stem cell transplant recipient who experiences severe hypogammaglobulinemia (IgG less than or equal to 400 mg/dL)
  • Hyperimmunoglobulinemia E syndrome (HIES) (Hyper-IgE syndromes, Job’s syndrome) when all of the following signs and symptoms are present:
    • Individual has eosinophilia (500 or more eosinophils/microL)
    • Individual has elevated serum IgE (>2000 IU/ml), with normal IgG, IgA, and IgM levels
    • Individual has eczema, recurrent staphylococcal lung infections, and/or skin abscesses documented in office or hospital charts
  • Human immunodeficiency virus (HIV)--infected individuals to reduce significant bacterial infection when all of the following criteria are met:
    • The individual is younger than 14 years of age.
    • The individual has entry CD4 lymphocyte counts greater than or equal to 200/mm³.
    • The individual is clinically symptomatic or asymptomatic, but is immunologically abnormal.
    • The individual has severe hypogammaglobulinema (serum IgG level less than 400 mg/dL) and/or functional antibody deficiency demonstrated by either poor specific antibody titers or recurrent bacterial infections.
    • The individual has recurrent serious bacterial infections, (i.e., two or more infections such as bacteremia, meningitis, or pneumonia in a 1-year period).
  • Kawasaki disease (mucocutaneous lymph node syndrome)
  • Neonatal hemochromatosis (neonatal alloimmune hepatitis):
    • Administration to pregnant women with history of pregnancy ending in documented neonatal hemochromatosis who are at risk for subsequent pregnancies ending in documented neonatal hemochromatosis
    • Administration to the neonate with documented neonatal hemochromatosis, combined with exchange transfusion
  • Primary immunodeficiency disorders (PIDD) when the individual has a confirmed genetic diagnosis or laboratory evidence of PIDD or the individual meets both of the following criteria:
    • Individual has a personal history of recurrent, antibiotic-refractory, bacterial infections of the ear (e.g., otitis media) or sinopulmonary infections (e.g., sinusitis, bronchitis/bronchiectasis, pneumonia), which are documented in office or hospital charts.
    • Individual has a deficiency of antibody response to at least one of the following antigens (e.g., proteins, polysaccharides, or viral antigens):
      • Polyvalent pneumococcal polysaccharide vaccine (e.g., Pneumovax 23), measured at the time of immunization and 4-8 weeks after vaccination.
        • A protective (normal) response to each pneumococcal serotype is defined as a titer equal to or greater than 1.3 mcg/mL antibody.
            1. For individuals ages 6 to 65 years, a normal response is defined as conversion of 70% of the serotypes tested with at least a 2-fold increase in the titers.
            2. For children 24 months through 5 years of age, a normal response is defined as the conversion of 50% or more of the serotypes tested with at least a 2-fold increase in the titers.
            3. (Note: When reported, the conversion factor for nanograms of antibody nitrogen per milliliter (ng N/mL) to antibody micrograms per milliliter is as follows: 160ng N/mL = 1 mcg/mL)
      • Protein antigens, tetanus/diphtheria vaccine measured at the time of immunization and 3 to 4 weeks after vaccination
        • A protective (normal) response is defined as any of the following:
            1. At least a 4-fold increase for protein antigens
            2. A serum diphtheria antitoxin level of 0.01 International Units (IU)/mL is the lowest level giving some degree of protection, and levels of at least 0.1 IU/mL are generally regarded as protective
            3. A protective level for Tetanus is 0.15 IU/mL
      The list of PIDDs includes, but is not limited to:
        1. Ataxia-telangectasia
        2. Autosomal recessive agammaglobulinemia
        3. Caspase 8 deficiency
        4. Common variable immunodeficiency (including TACI and ICOS mutation)
        5. DiGeorge syndrome
        6. DOCK (dedicator of cytokinesis 8) deficiency
        7. Griscelli syndrome
        8. Hypogammaglobulinemia, persistent (IgG less than or equal to 400 mg/dL or less than two standard deviations from normal)
        9. IgG-subclass deficiency (deficiency of one or more IgG subclasses to levels less than 2 standard deviations below the age-specific mean, in the presence of normal or near-normal total IgG levels. These levels must be assessed on at least two occasions while the individual is free of acute infections).
        10. NEMO (mutations in IKK-gamma) deficiency
        11. Nijmegen breakage syndrome
        12. Purine nucleoside phosphorylase [PNP] deficiency
        13. Selective IgA deficiency with IgG subclass deficiency (reduced serum IgA levels [less than 7mg/dL] and normal IgG and IgM levels)
        14. Severe combined immunodeficiency (SCID)
        15. Specific antibody deficiency (Selective antibody deficiency) with normal immunoglobulins
          1. Individual has impaired production of specific antibodies to polysaccharide antigens after vaccination and normal responses to protein antigens
        16. Transient hypogammaglobulinemia of infancy
        17. WHIM (warts, hypogammaglobulinemia, immunodeficiency, and myelokathexis) syndrome
        18. Wiskott-Aldrich syndrome
        19. X-linked agammaglobulinemia (aka, Bruton's agammaglobulinemia, congenital agammaglobulinemia)
        20. X-linked and autosomal recessive hyper IgM syndromes
        21. X-linked immunodeficiency
        22. X-linked lymphoproliferative disease
  • Preterm and/or low-birth-weight neonates as prevention for serious infections (including sepsis, urinary tract infection, soft-tissue infections or cellulitis) when severe hypogammaglobulinemia (IgG less than or equal to 400 mg/dL) is present
  • Solid organ transplant and antibody-mediated rejection (AMR) when the individual has had a transplant

Infectious Disease
  • Toxic shock syndrome
    • IVIG may be considered an adjunct in the treatment of staphylococcal or streptococcal toxic shock syndrome.

Neurological and Musculoskeletal Disorders
  • Acute disseminated encephalomyelitis (ADEM)
    • Rescue therapy for individuals unresponsive/refractory to, intolerant of, or who have a contraindication to, corticosteroids.
  • Chronic inflammatory demyelinating polyneuropathies (CIDP)
    • There must be objective clinical evidence to support the diagnosis of CIDP (such as impaired function measured by a standard clinical scale at the time of initial therapy [e.g., slowing of nerve conduction velocity on electromyography, nerve conduction studies]).
  • Dermatomyositis and polymyositis (PM) when all of the following criteria are met:
    • There must be clinical evidence to support the diagnosis, as well as a biopsy (or unequivocal diagnostic features through history, exam, and EMG/NCS studies) performed to verify the diagnosis of dermatomyositis or polymyositis.
    • The individual has impaired function (such as a decrease in muscle strength and/or electromyography abnormalities measured by a standard clinical scale at the time of initial therapy) and/or elevated serum Creatine Kinase (CK) levels.
    • The individual is unresponsive/refractory to, intolerant of, or has a contraindication to, a four month trial of steroids and/or immunosuppressants.
  • Guillain-Barre syndrome
    • The individual's function is impaired (e.g., unable to stand or walk without aid), measured by a standard clinical scale and/or objective findings on a physical exam at the time of initial therapy.
  • Intractable seizures and epilepsies in infants and children
    • The individual is unresponsive/refractory to, intolerant of, or has a contraindication to, all standard therapies (e.g., antiepileptic drugs and corticosteroids).
  • Lambert-Eaton myasthenic syndrome
    • The individual is unresponsive/refractory to, intolerant of, or has a contraindication to, other standard therapies (e.g., plasma exchange, corticosteroids or other immunosuppressants, cholinesterase inhibitors, or 3,4-diaminopyridine [DAP]).
  • Multifocal motor neuropathy (MMN)
    • The individual has progressive, symptomatic MMN that has been diagnosed on the basis of electrophysiologic findings that rule out other possible conditions that may not respond to IVIG.
  • Myasthenia gravis syndrome when all of the following criteria are met:
    • The individual has severely impaired function (such as a risk of respiratory failure) measured by a standard clinical scale and/or objective findings on a physical exam at the time of initial therapy.
    • The individual is refractory to other standard therapies (e.g., plasmapheresis) or to standard pharmacological therapies (e.g., corticosteroids, azathioprine, cyclosporine, cyclophosphamide, cholinesterase inhibitors) given in therapeutic doses over at least 8 weeks or is intolerant of, or has a contraindication to, standard therapies.
  • Myasthenic crisis (i.e., an acute episode of respiratory muscle weakness) in individuals with contraindication to plasma exchange
  • Neuromyelitis Optica (NMO) (Devic’s Syndrome)
    • The individual is unresponsive/refractory to, intolerant of, or has a contraindication to, corticosteroids and azathioprine.
  • Rasmussen’s encephalitis
    • In patients with intractable focal motor seizures and progressive neurologic deterioration (dementia, hemiparesis)
  • Relapsing-remitting multiple sclerosis (MS) when all of the following criteria are met:
    • The individual has impaired function measured by a standard clinical scale and/or objective findings on a physical exam at the time of initial therapy.
    • The individual is refractory to other standard therapies (e.g., interferons) given in therapeutic doses over at least 3 months, or is intolerant of, or has a contraindication to, standard therapies.
    • The individual has an acute relapse of the disease.
  • Stiff-person syndrome
    • The individual is refractory to other standard therapies (e.g., muscle relaxants, benzodiazepines, and gabapentin-related medications)
  • Systemic lupus erythematosus (SLE) in an individual who failed previous treatment such as corticosteroids and immunosuppressive agents, or treatment was ineffective or contraindicated

CONTINUATION OF THERAPY FOR IVIG, SCIG

Once treatment with immune globulin (IVIG, SCIG) is initiated, documentation of the individual's progress is required. If there is initial improvement and continued treatment is necessary, then objective clinical assessment to monitor the progress is required. Objective monitoring may be done with any accepted clinical method such as the Medical Research Council (MRC) scale, Rankin score, Activities of Daily Living (ADL) scores, and/or objective findings on physical exam. Changes in these measures and the relationship of the change to immune globulin use are expected to be documented clearly. Subjective improvement is insufficient to continue immune globulin treatment. Clinical monitoring takes clear precedence over laboratory monitoring. If clinical improvement is evident, then laboratory monitoring solely to guide immune globulin therapy is not necessary.

NOT MEDICALLY NECESSARY USES FOR SCIG

Coverage of non-preferred products (e.g., Cutaquig, Cuvitru, Hizentra®, HyQvia, and Xembify) are considered not medically necessary and, therefore, not covered for the treatment of PIDD because there is no reliable evidence of the superiority of any one brand compared to others and more cost-effective alternatives are available. An exception would be considered if the individual has had a documented failure, contraindication*, or intolerance to the subcutaneous administration of the Company's preferred subcutaneous products (i.e., Gammagard Liquid®, Gammaked®, or Gamunex-C®).

EXPERIMENTAL/INVESTIGATIONAL USES FOR IVIG, SCIG

All other uses of immune globulin (IVIG, SCIG), including the list below, are considered experimental/investigational and, therefore, not covered unless the indication is supported as an accepted off-label use, as defined in the policy on off-label coverage for prescription drugs and biologics.
  • Alzheimer's disease
  • Autism
  • Autoimmune encephalopathy
  • Hemolytic uremic syndrome
  • Multiple sclerosis: Primary Progressive or Secondary Progressive
  • Myocarditis (Acute)
  • Neonatal sepsis treatment
  • Paraneoplastic limbic encephalitis
  • Pediatric Acute-onset Neuropsychiatric Syndrome (PANS)
  • Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS)
  • Pericarditis refractory, recurrent
  • Peripheral neuropathy of unknown etiology with peroneal muscle atrophy
  • Postural tachycardia syndrome (POTS)
  • Yellow nail syndrome

NOT ELIGIBLE FOR REIMBURSEMENT

Vivaglobin® is no longer manufactured and has been withdrawn from market; therefore, it is not eligible for reimbursement.

DOSING AND FREQUENCY REQUIREMENTS

The Company reserves the right to modify the Dosing and Frequency Requirements listed in this Policy to ensure consistency with the most recently published recommendations for the use of IVIG and SCIG. Changes to these guidelines are based on a consensus of information obtained from resources such as, but not limited to the US Food and Drug Administration (FDA), drug manufacturer’s guidelines, Company- recognized authoritative pharmacology compendia, or published peer-reviewed clinical research. The professional provider must supply supporting documentation (i.e., published peer-reviewed literature) in order to request coverage for an amount of IVIG and SCIG outside of the Dosing and Frequency Requirements listed in this policy. For a list of Company-recognized pharmacology compendia and criteria for peer-reviewed clinical research, view our policy on off-label coverage for prescription drugs and biologics.

Accurate member information is necessary for the Company to approve the requested dose and frequency of these drugs. If the member’s dose, frequency, or regimen changes (based on factors such as changes in member weight or incomplete therapeutic response), the provider must submit those changes to the Company for a new approval based on those changes as part of the precertification process. The Company reserves the right to conduct post-payment review and audit procedures for any claims submitted for IVIG and SCIG.

Refer to Attachment A for dosing and frequency requirements for IVIG and SCIG.

REQUIRED DOCUMENTATION

When coverage of IVIG and SCIG is requested outside of the Dosing and Frequency Guidelines listed in this policy, the prescribing professional provider must supply documentation (i.e., published peer-reviewed literature) to the Company that supports this request.

The Company may conduct reviews and audits of services to our members regardless of the participation status of the provider. Medical record documentation must be maintained on file to reflect the medical necessity of the care and services provided. These medical records may include but are not limited to: records from the professional provider’s office, hospital, nursing home, home health agencies, therapies, and test reports.

PRESCRIPTION (ORDER) REQUIREMENTS
Before submitting a claim to the Company, the supplier must have on file a timely, appropriate, and complete order for each item billed that is signed and dated by the professional provider who is treating the member. Requesting a provider to sign a retrospective order at the time of an audit or after an audit for submission as an original order, reorder, or updated order will not satisfy the requirement to maintain a timely professional provider order on file.

PROOF OF DELIVERY
Medical record documentation must include a contemporaneously prepared delivery confirmation or member’s receipt of supplies and equipment. The medical record documentation must include a copy of delivery confirmation if delivered by a commercial carrier and a signed copy of delivery confirmation by member/caregiver if delivered by the DME supplier/provider. All documentation is to be prepared contemporaneous with delivery and be available to the Company upon request.

CONSUMABLE SUPPLIES
The durable medical equipment (DME) supplier must monitor the quantity of accessories and supplies an individual is actually using. Contacting the individual regarding replenishment of supplies should not be done earlier than approximately seven days prior to the delivery/shipping date. Dated documentation of this contact with the individual is required in the individual’s medical record. Delivery of the supplies should not be done earlier than approximately five days before the individual would exhaust their on-hand supply.

If required documentation is not available on file to support a claim at the time of an audit or record request, the durable medical equipment (DME) supplier may be required to reimburse the Company for overpayments.
Guidelines

BLACK BOX WARNINGS

Refer to the specific manufacturer's prescribing information for any applicable Black Box Warnings.

BENEFIT APPLICATION

Subject to the terms and conditions of the applicable benefit contract, intravenous immune globulin (IVIG) and subcutaneous immune globulin (SCIG) are covered under the medical benefits of the Company’s products when the medical necessity criteria, dosing and frequency requirements, and precertification/preapproval requirements listed in this medical policy are met.

However, indications that are identified in this policy as experimental/investigational are not eligible for coverage or reimbursement by the Company.

US FOOD AND DRUG ADMINISTRATION (FDA) STATUS

The FDA has approved numerous formulations of IVIG and SCIG.

On June 7, 1984, the FDA approved Carimune NF® IVIG (human) lyophilized powder product for the treatment of primary immune deficiency diseases (PIDD) and acute and chronic immune thrombocytopenic purpura (ITP).

In 1994, the FDA approved Gammagard S/D® for the treatment of PIDD. Supplemental approvals for Gammagard S/D® have since been issued by the FDA.

In 2003, the FDA approved both Gamunex-C® and Gammaked® immune globulin intravenous (IVIG) (human) 10 percent liquid products for the treatment of PIDD via intravenous or subcutaneous administration. Supplemental approvals for both products have since been issued by the FDA.

On December 15, 2003, the FDA approved Flebogamma® IVIG (human) for the treatment of PIDD. Supplemental approvals for Flebogamma® have since been issued by the FDA.

On May 21, 2004, the FDA approved Octagam® IVIG (human) 5 percent liquid product for the treatment of PIDD. Supplemental approvals for Octagam® have since been issued by the FDA.

In 2005, the FDA approved Gammagard Liquid® IVIG (human) 10 percent liquid product for the treatment of PIDD via intravenous or subcutaneous administration. Supplemental approvals for Gammagard Liquid® have since been issued by the FDA.

On January 9, 2006, the FDA approved immune globulin subcutaneous (SCIG), human (Vivaglobin®), for the prevention of serious infections in individuals with PIDD. In 2011, this product was discontinued and replaced with Hizentra®.

On July 26, 2007, the FDA approved Privigen®, IVIG (human) 10 percent liquid product for the treatment of PIDD and chronic ITP.

On September 17, 2009 the FDA approved Gammaplex® IVIG (human) 5 percent liquid product for the treatment of PIDD. A subsequent approval for the treatment of chronic ITP was granted on March 8, 2013.

On March 4, 2010, the FDA approved Hizentra® SCIG (human) 20 percent liquid product for the treatment of PIDD. Supplemental approvals for Hizentra® have since been issued by the FDA.

On December 19, 2012, the FDA approved Bivigam® IVIG (human) 10 percent liquid product for the treatment of PIDD.

On September 12, 2014, the FDA approved HyQvia SCIG (human) with Recombinant Human Hyaluronidase) 10 percent liquid product for the treatment of PIDD.

On September 13, 2016, the FDA approved Cuvitru SCIG (human) 20 percent solution for the treatment of PIDD.

On August 2, 2018, the FDA approved Panzyga®, Immune Globulin Intravenous, human-ifas, 10% Solution for the treatment of PIDD and chronic ITP.

On December 12, 2018, the FDA approved Cutaquig, Immune Globulin Subcutaneous (Human), 16.5% Solution for the treatment of PIDD.

On April 1, 2019, the FDA approved AscenivTM, Immune Globulin Intravenous, human-slra, 10% Solution for the treatment of PIDD.

On July 3, 2019, the FDA approved Xembify, Immune Globulin Subcutaneous, human-klhw, 20% Solution for the treatment of PIDD.

Description

Intravenous immune globulin (IVIG) is a sterile solution of plasma proteins containing immune globulin G (IgG) antibodies from pooled human plasma. The preparation contains no less than 90 percent of immune globulin consisting of all IgG substances and trace amounts of immune globulin A (IgA) and immune globulin M (IgM). IVIG supplies a broad spectrum of IgG antibodies against a wide variety of bacterial and viral agents. IVIG has been used to correct immune deficiencies and to increase immunity in diseases considered to have an autoimmune basis. IVIG is administered in this form and with this route of administration when immediate increase or higher levels of circulating immune globulin are required and cannot be attained from intramuscular administration, or when the latter is contraindicated.

The US Food and Drug Administration (FDA) has approved the subcutaneous infusion preparation of an immune globulin product (SCIG) for the prevention of serious infections in those with primary immunodeficiency disease (PIDD). SCIG is administered subcutaneously using an infusion pump, usually on a weekly basis, in CIDP and PIDD. SCIG may be an option for individuals who have received IVIG and wish to transition to the subcutaneous infusion route. When transitioning from IVIG to a SCIG formulation, the weekly dose of Ig must be increased for some of the SCIG formulations; hence, SCIG formulations utilize more grams of Ig compared to IVIG formulations.

Note: There are a few formulations of IVIG that may be administered via subcutaneous infusion for the indication of PIDD (e.g., Gammagard Liquid®, Gamunex-C®, Gammaked®).

OFF-LABEL INDICATIONS

There may be additional indications contained in the Policy section of this document due to evaluation of criteria highlighted in the Company’s off-label policy, and/or review of clinical guidelines issued by leading professional organizations and government entities.
References

REFERENCES FOR MEDICALLY NECESSARY INDICATIONS


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REFERENCES FOR EXPERIMENTAL/INVESTIGATIONAL INDICATIONS

Alzheimer's Disease

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Kile S, Au W, Parise C, et al. IVIG treatment of mild cognitive impairment due to Alzheimer’s disease: a randomized double-blinded exploratory study of the effect on brain atrophy, cognition and conversion to dementia. J Neurol Neurosurg Psychiatry. 2017;88:106-112.

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Relkin NR, Szabo P, Adamiak B, et al. 18-Month study of intravenous immunoglobulin for treatment of mild Alzheimer disease. Neurobiol Aging. 2009 Nov;30(11):1728-36.

Relkin NR, Thomas RG, Rissman RA, et al. A phase 3 trial of IV immunoglobulin for Alzheimer disease. Neurology. 2017;88:1768-1775.

Autism

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Weissman L, Bridgemohan C. Autism spectrum disorders in children and adolescents Complementary and alternative therapies. 08/23/18. UpToDate Website. Available at http://www.uptodate.com/contents/autism-spectrum-disorders-in-children-and-adolescents-complementary-and-alternative-therapies?source=search_result&search=seizures+AND+IVIG&selectedTitle=5%7E150 . Accessed February 13, 2019.

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Autoimmune Encephalopathy

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Hemolytic uremic syndrome

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Mayo Clinic. Hemolytic uremic syndrome. July 2016. Available at: http://www.mayoclinic.org/diseases-conditions/hemolytic-uremic-syndrome/diagnosis-treatment/treatment/txc-20204170. Accessed February 13, 2019.

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Multiple sclerosis: Primary Progressive or Secondary Progressive

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Perez EE, Orange JS, Bonilla F, et al. Update on the use of immunoglobulin in human disease: A review of the evidence. J Allergy Clin Immunol. 2017;139:S1-S45.

Myocarditis (Acute)

Allan CK, Fulton DR. Treatment and prognosis of myocarditis in children. UpToDate Website. 09/2018. Available at: https://www.uptodate.com/contents/treatment-and-prognosis-of-myocarditis-in-children?source=search_result&search=myocarditis&selectedTitle=5~150. Accessed February 14, 2019.

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English RF, Janosky JE, Ettedqui JA, et al. Outcomes for children with acute myocarditis. Cardiol Young. 2004;14:488-493.

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Gullestad L, Aass H, Fjeld JG, et al. Immunomodulating therapy with intravenous immunoglobulin in patients with chronic heart failure. Circulation. 2001;103:220-225.

Haque A, Bhatti S, Siddiqui FJ. Intravenous immune globulin for severe acute myocarditis in children. Indian Pediatr. 2009;46:810-811.

Huang X, Sun Y, Su G, Li Y, Shuai X. Intravenous Immunoglobulin Therapy for Acute Myocarditis in Children and Adults. Int Heart J. 2019 Mar 20;60(2):359-365.

Hufnagel G, Pankuweit S, Richter A, Schönian U, Maisch B. The European Study of Epidemiology and Treatment of Cardiac Inflammatory Diseases (ESETCID). First epidemiological results. Herz. 2000 May;25(3):279-85.

Kim HJ, Yoo GH, Kil HR. Clinical outcome of acute myocarditis in children according to treatment modalities. Korean J Pediatr. 2010;53:745-752.

Kindermann I, Barth C, Mahfoud F, et al. Update on myocarditis. J Am Coll Cardiol. 2012;59:779-792.

Kishimoto C, Shioji K, Hashimoto T, et al. Therapy with immunoglobulin in patients with acute myocarditis and cardiomyopathy. Analysis of leukocyte balance. Heart Vessels. 2014;29:336-342.

Klugman D, Berger JT, Sable C’A, et al. Pediatric patients hospitalized with myocarditis: a multi-institutional analysis. Pediatr Cardiol. 2010;31:222-228.

Lee KJ, McCrindle DJ, Bohn GJ, et al. Clinical outcomes of acute myocarditis in childhood. Heart. 1999;82:226-233.

McNamara DM, Holubkov R, Starling RC, et al. Controlled trial of intravenous immune globulin in recent-onset dilated cardiomyopathy. Circulation. 2001;103:2254-2259.

Prasad AN, Chaudhary S. Intravenous immunoglobulin in children with acute myocarditis and/or early dilated cardiomyopathy. Indian Pediatr. 2014;51:583-584.

Robinson J, Hartling L, Vandermeer B, et al. Intravenous immunoglobulin for presumed viral myocarditis in children and adults. Cochrane Database Syst Rev. 2015 May 20; (5): CD004370.

Neonatal sepsis treatment

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Edwards MS. Management and outcome of sepsis in term and late preterm infants. UpToDate Website. 10/16/18. Available at: https://www.uptodate.com/contents/management-and-outcome-of-sepsis-in-term-and-late-preterm-infants?source=search_result&search=neonatal%20sepsis&selectedTitle=2~91. Accessed February 14, 2019.

Fleisher TA. Treatment of neonatal sepsis with immune globulin. Pediatrics. 2012:130(1).

INIS Collaborative Group. Treatment of neonatal sepsis with intravenous immune globulin. N Engl J Med. 2011;365:1201-1211.

Ohlsson A, Lacy JB. Intravenous immunoglobulin for suspected or proven infection in neonates. Cochrane Database Syst Rev. 2015 Mar 27; (3):CD01239.

Weisman LE, Pammi M. Treatment and prevention of bacterial sepsis in preterm infants <34 weeks gestation. 04/04/2019. Available at: https://www.uptodate.com/contents/treatment-and-prevention-of-bacterial-sepsis-in-preterm-infants-less-than34-weeks-gestation?search=bacterial%20sepsis%20in%20preterm&source=search_result&selectedTitle=1~150&usage_type=default&display_rank=1 . Accessed April 5, 2019.

Wong PH, White KM. Impact of immunoglobulin therapy in pediatric disease: A review of immune mechanisms. Clinic Rev Allerg Immunol. 2017;51:303-314.

Paraneoplastic Limbic Encephalitis

Blaes F, Strittmatter M, Merkelbach S, et al. Intravenous immunoglobulins in the therapy of paraneoplastic neurological disorders. J Neurol. 1999;246 299-203.

Dalmau J, Rosenfeld MR, et al. Paraneoplastic and autoimmune encephalitis. UpToDate Website. 10/2018. Available at: http://www.uptodate.com/contents/paraneoplastic-and-autoimmune-encephalitis?source=search_result&search=paraneoplastic+limbic+encephalitis&selectedTitle=1%7E2#H2380193 . Accessed February 13, 2019.

Derry CP, Wilkie MD, Al-Shahi S, et al. Autoimmune limbic encephalitis. Clin Med. 2011;11 476-478.

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Graus F, Keime-Guibert F, Rene R, et al. Anti-Hu-associated paraneoplastic encephalomyelitis analysis of 200 patients. Brain. 2001;124 1138-1148.

Keime-Guibert F, Graus F, Fleury A, et al. Treatment of paraneoplastic neurological syndromes with antineuronal antibodies (anti-Hu, anti-Yo) with a combination of immunoglobulins, cyclophosphamide, and methylprednisolone. J Neurol Neurosurg Psychiatry. 2000;68 479-482.

NIH. GARD Genetic & Rare Diseases Information Center. Limbic encephalitis. 2016. Available at: https://rarediseases.info.nih.gov/diseases/8742/limbic-encephalitis. Accessed February 13, 2019.

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Pediatric Acute-onset Neuropsychiatric Syndrome (PANS) and Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections (PANDAS)

Alexander AA, Patel NJ, Southammakosane CA, Mortensen MM. Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS): an indication for tonsillectomy. Int J Pediatr Otorhinolaryngol. 2011;75(6):872-3. Epub 2011 Apr 3.

American Academy of Allergy, Asthma and Immunology. Position statement on the appropriate use of intravenously administered immunoglobulin (IGIV). January 2005. Available at: https://www.aaaai.org/Aaaai/media/MediaLibrary/PDF%20Documents/Practice%20and%20Parameters/IGIV-2005.pdf . Accessed February 15, 2019.

Chiarello F, Spitoni S, Hollander E, et al. An expert opinion on PANDAS/PANS: highlights and controversies. Int J Psychiatry Clin Pract. 2017;21:91-98.

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Farhood Z, Ong AA, Discolo CM. PANDAS: A systematic review of treatment options. Int J Pediatr Otorhinolaryngol. 2016;89:149-53.

Frankovich J, Swedo SE, Murphy TK, et al. Clinical Management of Pediatric Acute-Onset Neuropsychiatric Syndrome: Part II—Use of Immunomodulatory Therapies. Journal of Child and Adolescent Psychopharmacology. 2017;27(7):1-16.

Gause C, Morris C, Vernekar S, Pardo-Villamizar C, Grados MA, Singer HS. Antineuronal antibodies in OCD: comparisons in children with OCD-only, OCD+chronic tics and OCD+PANDAS. J Neuroimmunol. 2009;214(1-2):118-24. Epub 2009 Jul 22.

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Hoekstra PJ, Minderaa RB, Kallenberg CG. Lack of effect of intravenous immunoglobulins on tics a double-blind placebo-controlled study. J Clin Psychiatry. 2004;65 537-542.

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Kovacevic M, Grant P, Swedo SE. Use of intravenous immunoglobulin in the treatment of twelve youths with pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections. J Child Adolesc Psychopharmacol. 2015 Feb;25(1):65-9.

Macerollo A, Martino D. Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections (PANDAS): An Evolving Concept. Tremor Other Hyperkinet Mov (N Y). 2013;3. pii: tre-03-167-4158-7. eCollection 2013.

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Moretti G, Pasquini M, Mandarelli G, et al. What every psychiatrist should know about PANDAS a review. Clin Pract Epidemiol Ment Health. 2008;4 13.

Morris CM, Pardo-Villamizar C, Grause CD, et al. Serum autoantibodies measured by immunofluorescence confirm a failure to differentiate PANDAS and Tourette syndrome from controls. J Neurol Sci. 2009;276(1-2) 45-8.

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Murphy TK, Kurlan R, Leckman J. The immunobiology of Tourette’s disorder, pediatric autoimmune neuropsychiatric disorders associated with Streptococcus, and related disorders A way forward. J Child Adolesc Psychopharmacol. 2010;20 317-331.

National Institute of Mental Health. PANDAS: Frequently asked questions about Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections. Last reviewed September 2016. Available at: https://www.nimh.nih.gov/health/publications/pandas/index.shtml#pub3. Accessed February 15, 2019.

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Perlmutter SJ, Leitman SF, Garvey MA, et al. Therapeutic plasma exchange and intravenous immunoglobulin for obsessive-compulsive disorder and tic disorders in childhood. Lancet. 1999;354 1153-1158.

Pichichero ME. PANDAS: Pediatric autoimmune neuropsychiatric disorder associated with group A streptococci. 01/15/19. UpToDate Website. Available at: https://www.uptodate.com/contents/pandas-pediatric-autoimmune-neuropsychiatric-disorder-associated-with-group-a-streptococci?source=search_result&search=PANDAs&selectedTitle=1~10 . Accessed February 15, 2019.

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Provon D, Nokes TJC, Agrawal S, et al. Clinical guidelines for immunoglobulin use. 2nd edition. May 30, 2008. UK Dept of Health.

Robinson P, Anderson D, Brouwers M, et al.; IVIG Hematology and Neurology Expert Panels. Evidence-based guidelines on the use of intravenous immune globulin for hematologic and neurologic conditions. Transfus Med Rev. 2007;21(2 Suppl 1):S3-8.

Schwartz J, Winters JL, Padmanabhan A, et al. Guidelines on the use of therapeutic apheresis in clinical practice-evidence-based approach from the Writing Committee of the American Society for Apheresis: the sixth special issue. J Clin Apher. 2013;28(3):145-284.

Shulman ST. Pediatric autoimmune neuropsychiatric disorders associated with streptococci (PANDAS): update. Curr Opin Pediatr. 2009;21(1):127-30.

Swedo SE, Lechman JF, Rose NR. From research subgroup to clinical syndrome Modifying the PANDAS criteria to describe PANS (Pediatric Acute-onset Neuropsychiatric Syndrome). Pediatr Therapeut. 2012;2 ISSN 2161-0665.

Swedo SE, Leonard HL, Garvey M, et al. Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections clinical description of the first 50 cases. Am J Psychiatry. 1998;155 264-271.

Swedo SE, Leonard HL, Rapoport JL. The pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection (PANDAS) subgroup: separating fact from fiction. Pediatrics. 2004;113(4):907.

Tan J, Smith CH, Goldman RD. Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections. Can Fam Physician. 2012;58(9):957-9.

Williams KA, Swedo SE, Farmer CA, et al. Randomized, Controlled Trial of Intravenous Immunoglobulin for Pediatric Autoimmune Neuropsychiatric Disorders Associated With Streptococcal Infections. J Am Acad Child Adolesc Psychiatry. 2016;55(10):860-867.e2.

Wong PH, White KM. Impact of immunoglobulin therapy in pediatric disease: A review of immune mechanisms. Clinic Rev Allerg Immunol. 2017;51:303-314.

Pericarditis refractory, recurrent

Alder Y, Charron P, Imazio M, et al. 2015 ESC Guidelines for the diagnosis and management of pericardial diseases. Eur Heart J. 2015;36:2921-2964.

Baskar S. Pediatric pericarditis. American College of Cardiology Website. 06/08/16. Available at: http://www.acc.org/latest-in-cardiology/articles/2016/06/08/11/43/pediatric-pericarditis?w_nav=LC. Accessed February 15, 2019.

Brown A, Kontzias A. The evolving relationship of cardiology and rheumatology in treating patients with recurrent pericarditis. American College of Cardiology Website. Oct 12, 2016. Available at: http://www.acc.org/latest-in-cardiology/articles/2016/10/11/11/58/the-evolving-relationship-of-cardiology-and-rheumatology-in-treating-patients-with-recurrent-pericarditis?w_nav=LC. Accessed February 15, 2019.

Cremer PC, Kumar A, Kontzias A, et al. Complicated pericarditis: Understanding risk factors and pathophysiology to inform imaging and treatment. J Am Coll Cardiol. 2016;68:2311-2328.

Dauphin C, Merlin E, Chalard A, et al. Recurrent pericarditis: current challenges and future prospects. Research Reports in Clinical Cardiology. 2016:7:99-108.

Del Fresno MR, Peralta JE, Granados MA, et al. Intravenous immunoglobulin therapy for refractory recurrent pericarditis. Pediatrics. 2014;134:1441-1446.

Galluzzo A, Imazio M. Advances in medical therapy for pericardial diseases. Expert Rev Cardiovasc Ther. 2018 Sep;16(9):635-643.

Imazio M, Adler Y, Charron P. Recurrent pericarditis: Modern approach in 2016. Curr Cardiol Rep. 2016;18:50-59.

Imazio M, Gaita F. Acute and Recurrent Pericarditis. Cardiol Clin. 2017 Nov;35(4):505-513.

Imazio M, Lazaros G, Picardi E, et al. Intravenous human immunoglobulins for refractory recurrent pericarditis: a systematic review of all published cases. J Cardiovasc Med. 2016;17:263-269.

Lotan D, Wasserstrum Y, Fardman A, et al. Usefulness of novel immunotherapeutic strategies for idiopathic recurrent pericarditis. Am J Cardiol. 2016;117:861-866.

Mookadam F. Pericardial diseases guidelines: Coming of age and making sense with evidence in the field of pericardiology. American College of Cardiology. 11/17/15. Available at: http://www.acc.org/latest-in-cardiology/articles/2015/11/16/07/19/pericardial-diseases-guidelines?w_nav=LC. Accessed February 15, 2019.

Moretti M, Buiatti A, Merlo M, et al. Usefulness of high-dose intravenous human immunoglobulins treatment for refractory recurrent pericarditis. Am J Cardiol. 2013;112:1493-1498.

Peterlana D, Puccetti A, Simeoni S, et al. Efficacy of intravenous immunoglobulin in chronic idiopathic pericarditis: report of 4 cases. Clin Rheumatol. 2005;24:18-21.

Schwier NC, Hale GM, Davies ML. Treatment of Adults with Idiopathic Recurrent Pericarditis: Novel Use of Immunotherapy. Pharmacotherapy. 2017 Mar;37(3):305-318.

Peripheral Neuropathy of Unknown Etiology with Peroneal Muscle Atrophy

Donofrio PD, Berger A, Brannagan TH, et al. Consensus Statement the use of intravenous immunoglobulin in the treatment of neuromuscular conditions report of the AANEM Ad Hoc Committee. Muscle Nerve. 2009;40 890-900.

Elovaara I, Apostolski S, van Doorn P, et al. EFNS guidelines for the use of intravenous immunoglobulin in treatment of neurological diseases EFNS task force on the use of intravenous immunoglobulin in treatment of neurological diseases. Eur J Neurol. 2008;15 893-908.

Ginsberg L, Malik O, Kenton AR, et al. Coexistent hereditary and inflammatory neuropathy. Brain. 2004;127 193-202.

National Institute of Neurological Disorders and Stroke. Charcot-Marie-Tooth disease fact sheet. 07/06/18. Available at: https://www.ninds.nih.gov/Disorders/Patient-Caregiver-Education/Fact-Sheets/Charcot-Marie-Tooth-Disease-Fact-Sheet#3092_6. Accessed February 15, 2019.

Schenone A, Nobbio L, Monti BM, et al. Inherited neuropathies. Curr Treat Options Neurol. 2011;13 160-179.

The Charcot-Marie-Tooth Association. What is CMT? Available at: https://www.cmtausa.org/understanding-cmt/what-is-cmt/. Accessed February 15, 2019.

Postural Tachycardia Syndrome (POTS)

Grubb BP. Postural tachycardia syndrome. Circulation. 2008;117(21) 2814-7.

Kaufmann H, Freeman R. Postural tachycardia syndrome. Up-To-Date Website. Updated 03/03/15. Available at: http://www.uptodate.com/contents/postural-tachycardia-syndrome. Accessed February 15, 2019.

Low PA, Sandroni P, Joyner M, et al. Postural tachycardia syndrome (POTS). J Cardiovasc Electrophysiol. 2009;20 352-358.

NINDS Postural Tachycardia Syndrome Information Page. National Institute of Neurological Disorders and Stroke. Updated 06/20/18. Available at: https://www.ninds.nih.gov/Disorders/All-Disorders/Postural-Tachycardia-Syndrome-Information-Page . Accessed February 15, 2019.

Yellow Nail Syndrome

Gupta S, Samra D, Yel L, Agrawal S. T and B cell deficiency associated with yellow nail syndrome. Scand J Immunol. 2012;75(3) 329-35.

Kurin M, Wiesen J, Mehta AC. Yellow nail syndrome: a case report and review of treatment options. Clin Respir J. 2017;11:405-410.

Maldonado F, Tazelaar HD, Wang CW, Ryu JH. Yellow nail syndrome analysis of 41 consecutive patients. Chest. 2008;134(2) 375-81.

Maldonado F, Ryu JH. Yellow nail syndrome. Curr Opin Pulm Med. 2009;15(4) 371-5.

National Association for Rare Disorders. Yellow nail syndrome. 2018. Available at: https://rarediseases.org/rare-diseases/yellow-nail-syndrome/. Accessed March 6, 2019.

Vignes S, Baran R. Yellow nail syndrome: A review. Orphanet J Rare Dis. 2017;12:42.

Zarogiannis S, Hatzoglou C, Molyvdas P-A, Gourgoulianis K. Yellow nail syndrome chylous pleural effusions defective lymph valves involved. Chest. 2008;134(6) 1353.




Coding

Inclusion of a code in this table does not imply reimbursement. Eligibility, benefits, limitations, exclusions, precertification/referral requirements, provider contracts, and Company policies apply.

The codes listed below are updated on a regular basis, in accordance with nationally accepted coding guidelines. Therefore, this policy applies to any and all future applicable coding changes, revisions, or updates.

In order to ensure optimal reimbursement, all health care services, devices, and pharmaceuticals should be reported using the billing codes and modifiers that most accurately represent the services rendered, unless otherwise directed by the Company.

The Coding Table lists any CPT, ICD-9, ICD-10, and HCPCS billing codes related only to the specific policy in which they appear.

CPT Procedure Code Number(s)

N/A


Professional and outpatient claims with a date of service on or before September 30, 2015, must be billed using ICD-9 codes. Professional and outpatient claims with a date of service on or after October 1, 2015, must be billed using ICD-10 codes.

Facility/Institutional inpatient claims with a date of discharge on or before September 30, 2015, must be billed with ICD-9 codes. Facility/Institutional inpatient claims with a date of discharge on or after October 1, 2015, must be billed with ICD-10 codes.


ICD - 10 Procedure Code Number(s)

N/A


Professional and outpatient claims with a date of service on or before September 30, 2015, must be billed using ICD-9 codes. Professional and outpatient claims with a date of service on or after October 1, 2015, must be billed using ICD-10 codes.

Facility/Institutional inpatient claims with a date of discharge on or before September 30, 2015, must be billed with ICD-9 codes. Facility/Institutional inpatient claims with a date of discharge on or after October 1, 2015, must be billed with ICD-10 codes.


ICD -10 Diagnosis Code Number(s)

See Attachment B


HCPCS Level II Code Number(s)

MEDICALLY NECESSARY


SUBCUTANEOUS IMMUNE GLOBULIN (SCIG)

J1555 Injection, immune globulin (cuvitru), 100 mg

J1559 Injection, immune globulin (Hizentra), 100 mg

J1561 Injection, immune globulin, (Gamunex/Gamunex-C/Gammaked), nonlyophilized (e.g., liquid), 500 mg

J1569 Injection, immune globulin, (Gammagard liquid), nonlyophilized, (e.g., liquid), 500 mg

The following code is used to represent HyQvia:
J1575 Injection, immune globulin/hyaluronidase, 100 mg immuneglobulin

The following codes are used to represent Cutaquig, Xembify:
C9399 Unclassified drugs or biologicals
J3590 Unclassified biologics

INTRAVENOUS IMMUNE GLOBULIN (IVIG)

J1459 Injection, immune globulin (Privigen), intravenous, non-lyophilized (e.g. liquid), 500 mg

J1556 Injection, immune globulin (bivigam), 500 mg

J1557 Injection, immune globulin (Gammaplex), intravenous, non-lyophilized (e.g. liquid), 500 mg

J1561 Injection, immune globulin, (Gamunex-C/Gammaked), non-lyophilized (e.g. liquid), 500 mg

J1568 Injection, immune globulin, (Octagam), intravenous, non-lyophilized (e.g. liquid), 500 mg

J1569 Injection, immune globulin, (Gammagard liquid), intravenous, non-lyophilized, (e.g. liquid), 500 mg

J1572 Injection, immune globulin, (Flebogamma/Flebogamma Dif), intravenous, non-lyophilized (e.g. liquid), 500 mg

S9338 Home infusion therapy, immunotherapy, administrative services, professional pharmacy services, care coordination, and all necessary supplies and equipment (drugs and nursing visits coded separately), per diem


The following code is used to represent CARIMUNE NF AND GAMMAGARD S/D:

J1566 Injection, immune globulin, intravenous, lyophilized (e.g. powder), not otherwise specified, 500 mg

The following code is used to represent AscenivTM and Panzyga® :

J1599 Injection, immune globulin, intravenous, nonlyophilized (e.g., liquid), not otherwise specified, 500mg


NOT ELIGIBLE FOR REIMBURSEMENT

THE FOLLOWING CODE REPRESENTS VIVAGLOBIN WHICH IS NO LONGER MANUFACTURED AND HAS BEEN WITHDRAWN FROM THE MARKET:


J1562 Injection, immune globulin (Vivaglobin), 100 mg



Revenue Code Number(s)

N/A

Coding and Billing Requirements


Cross References

Attachment A: Immune Globulin Intravenous (IVIG), Subcutaneous (SCIG)
Description: Dosing and Frequency Requirements

Attachment B: Immune Globulin Intravenous (IVIG), Subcutaneous (SCIG)
Description: ICD-10 DIAGNOSIS CODES



Related Documents


Policy History

Revisions from 08.00.13v
10/21/2019This policy was updated to communicate the Company's coverage criteria, including Dosing and Frequency, of the new SCIG product, Xembify. Two additional examples of Primary immunodeficiency diseases were added for IVIG and SCIG: Transient hypogammaglobulinemia of infancy and Purine nucleoside phosphorylase (PNP) deficiency. The indication of "Acquired (secondary) hypogammaglobulinemia in oncologic conditions" has been expanded to include "Other malignant diseases with associated hypogammaglobulinemia in an individual who has a high risk of serious, recurrent bacterial infections."

Revisions from 08.00.13u
06/17/2019This Policy was revised with the following changes:
  • The following new SCIG product was added: Cutaquig
  • The following new IVIG products were added: AscenivTM, Panzyga®.
  • New FDA-approved indication for SCIG (e.g., Hizentra®) for CIDP was added.
  • Scleromyxedema – Changed to first-line therapy
  • New indication for IVIG, per Novitas L35093, for Systemic Capillary Leak Syndrome (SCLS) or Clarkson's Disease: IVIG is considered medically necessary and, therefore, covered in individuals with Systemic Capillary Leak Syndrome (SCLS) or Clarkson's Disease when associated with monoclonal gammopathy and used for prophylaxis to increase survival
  • New indication for IVIG: Chimeric antigen receptor (CAR) T cell therapy (e.g., tisagenlecleucel [Kymriah™], axicabtagene ciloleucel [Yescarta™]) acquired hypogammaglobulinemia when the individual has an IgG level of less than 600 mg/dL.
  • Criteria changes for Preterm and/or low-birth-weight neonates with severe hypogammaglobulinemia
  • Intractable seizures and epilepsies in infants: expanded coverage to children
  • Lambert-Eaton: plasma exchange was added an as example of prior therapies.
  • Neuromyelitis Optica (NMO) (Devic’s Syndrome): Removed plasma exchange as an example of a prior therapy. Added azathioprine as an example of a prior therapy.
  • NOT MEDICALLY NECESSARY USES FOR SCIG: clarification that this statement is for the treatment of PIDD only, not CIDP.

Hemolytic uremic syndrome coverage changed from Medically Necessary to Experimental/Investigational.

The following indications were added to the Experimental/Investigational Coverage Section:
  • Multiple sclerosis: Primary Progressive or Secondary Progressive
  • Myocarditis (Acute)
  • Neonatal sepsis treatment
  • Pediatric Acute-onset Neuropsychiatric Syndrome (PANS)
  • Pericarditis refractory, recurrent

The following CPT codes were removed from the policy: 90283, 90284

Attachment B: Dosage and Frequency
SCIG Section:
PIDD Induction dosing was expanded from 100-150mg/kg/weekly to 100-200mg/kg/weekly.
PIDD: Cutaquig dosing was added.
CIDP: New Indication. Hizentra dosing was added.

IVIG Section:
Dosing and Frequency were added/adjusted for the following IVIG indications:
  • Scleromyxedema
  • Systemic Capillary Leak Syndrome (SCLS) or Clarkson's Disease
  • Chimeric antigen receptor (CAR) T cell therapy
  • Antibody-Mediated Rejection (AMR)
  • Autoimmune neutropenia
  • Guillain-Barre syndrome
  • Myasthenia gravis syndrome
  • Neuromyelitis Optica (NMO) (Devic’s Syndrome)

Revisions from 08.00.13t
01/01/2018This policy has been identified for the HCPCS code update, effective 01/01/2018.

The following NOC code has been removed from this policy and is replaced by the following HCPCS code:
REMOVED: J3590 Unclassified biologics
REPLACED WITH: J1555 Injection, immune globulin (cuvitru), 100 mg



Effective 10/05/2017 this policy has been updated to the new policy template
format.
Version Effective Date: 10/21/2019
Version Issued Date: 10/21/2019
Version Reissued Date: N/A

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