Notification



Notification Issue Date:



Medical Policy Bulletin


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

Policy #:08.00.13t

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.

MEDICALLY NECESSARY

SUBCUTANEOUS IMMUNE GLOBULIN (SCIG)
Company-Designated Preferred Products

Cuvitru, Hizentra®, and HyQvia 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 subcutaneously. Although there are several brands of IVIG and SCIG on the market approved for the treatment of primary immunodeficiency disorders (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: Cuvitru, Hizentra®, HyQvia.

Subcutaneous immune globulin (SCIG) (e.g., Cuvitru, Hizentra®, HyQvia) 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
  • 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. Selective IgA deficiency with IgG subclass deficiency (reduced serum IgA levels [less than 7mg/dL] and normal IgG and IgM levels)
      13. Severe combined immunodeficiency (SCID)
      14. 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
      15. WHIM (warts, hypogammaglobulinemia, immunodeficiency, and myelokathexis) syndrome
      16. Wiskott-Aldrich syndrome
      17. X-linked agammaglobulinemia (aka, Bruton's agammaglobulinemia, congenital agammaglobulinemia)
      18. X-linked and autosomal recessive hyper IgM syndromes
      19. X-linked immunodeficiency
      20. X-linked lymphoproliferative disease

INTRAVENOUS IMMUNE GLOBULIN (IVIG)
Use of intravenous immune globulin (IVIG) therapy (e.g., Bivigam®, Gammaplex®, Octagam®, Flebogamma®, Privigen®, Carimune NF®, Gammagard S/D®, Gammagard Liquid®, Gammaked®, Gamunex-C®) 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 in an individual who failed conventional therapy

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

Immunodeficiency Syndromes, Primary and Secondary
  • Acquired hypogammaglobulinemia in oncologic conditions:
    • 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
  • 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)
  • Hemolytic uremic syndrome
  • 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 400mg/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. Selective IgA deficiency with IgG subclass deficiency (reduced serum IgA levels [less than 7mg/dL] and normal IgG and IgM levels)
        13. Severe combined immunodeficiency (SCID)
        14. 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
        15. WHIM (warts, hypogammaglobulinemia, immunodeficiency, and myelokathexis) syndrome
        16. Wiskott-Aldrich syndrome
        17. X-linked agammaglobulinemia (aka, Bruton's agammaglobulinemia, congenital agammaglobulinemia)
        18. X-linked and autosomal recessive hyper IgM syndromes
        19. X-linked immunodeficiency
        20. X-linked lymphoproliferative disease
  • Preterm and/or low-birth-weight neonates with severe hypogammaglobulinemia as prevention or adjunct treatment for serious infections, including sepsis, urinary tract infection, soft-tissue infections or cellulitis.
  • Secondary (acquired) humoral immunodeficiency (e.g., medical therapy--induced hypogammaglobulinemia in solid organ transplantation, hematopoietic cell transplantation, and malignant and autoimmune diseases)
  • 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
    • 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., 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 or plasma exchange.
  • 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., Cuvitru, Hizentra®, HyQvia) are considered not medically necessary and, therefore, not covered 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
  • Paraneoplastic limbic encephalitis
  • Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS)
  • 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.

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.

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. 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


Alzueta, IJ and Matamoros, FN. Common Variable Immunodeficiency. Review. Allergol Immunopathol (Madr). 2001 May-Jun;29(3) 113-8.

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American Academy of Pediatrics Subcommittee on Hyperbilirubinemia. Management of hyperbilirubinemia in the newborn infant 35 or more weeks of gestation. Pediatrics. 2004;114(1) 297-316.

American Hospital Formulary Service (AHFS). Drug Information 2016. Immune Globulin. updated 12/09/11. [Lexicomp Online Web site]. Available at: http://online.lexi.com/lco/action/home [via subscription only]. Accessed June 13, 2016.

Bakker J, Metz L. Devic’s neuromyelitis optica treated with intravenous gamma globulin (IVIG). Can J Neurol Sci. 2004;31 265-267.

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Centers for Medicare and Medicaid Services (CMS). Medicare Benefit Policy Manual. Chapter 15 – Covered Medical and Other Health Services. 50.6 – Coverage of Intravenous Immune Globulin for Treatment of Primary Immune Deficiency Diseases in the Home. Rev. 194, Issued: 09-03-14. Available at: http://www.cms.gov/Regulations-and-Guidance/Guidance/Manuals/Internet-Only-Manuals-IOMs-Items/CMS012673.html . Accessed August 9, 2016.

Centers for Medicare and Medicaid Services (CMS). National Coverage Determination (NCD). 250.3 NCD for intravenous immune globulin for the treatment of autoimmune mucocutaneous blistering diseases. [CMS Web Site]. 10/01/02. Available at: http://www.cms.gov/medicare-coverage-database/details/ncd-details.aspx?NCDId=158&ncdver=1&CoverageSelection=Both&ArticleType=All&PolicyType=Final&s=Pennsylvania&KeyWord=Immune+Globulin&KeyWordLookUp=Title&KeyWordSearchType=And&bc=gAAAABAAAAAAAA%3d%3d& . Accessed May 27, 2016.

Dalakas M. Intravenous immunoglobulin in autoimmune neuromuscular diseases. JAMA. 2004;291(19) 2367-75.

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Elovaara I, Kuusisto H, Wu X, et al.Intravenous immunoglobulins are a therapeutic option in the treatment of multiple sclerosis relapse. Clin Neuropharmacol. 2011;34(2) 84-9.

Elsevier’s Gold Standard Clinical Pharmacology Compendium. Immune Globulin IV, IVIG, IGIV. [Clinical Key Web site]. 02/01/16. Available at: https://www.clinicalkey.com/#!/content/drug_monograph/6-s2.0-311 [via subscription only]. Accessed June 13, 2016.

Elsone L, Panicker J, Mutch K, et al. Role of intravenous immunoglobulin in the treatment of acute relapses of neuromyelitis optica: experience in 10 patients. Mult Scler. 2014;20(4):501-4. Epub 2013 Aug 28.

Fazekas F, Lublin FD, Li D, et al; PRIVIG Study Group; UBC MS/MRI Research Group. Intravenous immunoglobulin in relapsing-remitting multiple sclerosis a dose-finding trial. Neurology. 2008;71(4) 265-71.

Feasby T, Banwell B, et al. Guidelines on the use of intravenous immune globulin for neurologic conditions. Transfus Med Rev. 2007;21(2 Suppl 1) S57-107.

Filippini G, Del Giovane C, Vacchi L, et al. mmunomodulators and immunosuppressants for multiple sclerosis: a network meta-analysis. Cochrane Database Syst Rev. 2013;(6):CD008933.

Fortin PM, Tejani AM, Bassett K, et al. Intravenous immunoglobulin as adjuvant therapy for Wegener's granulomatosis. Cochrane Database Syst Rev. 2013;1:CD007057.

Gammaked®. package insert. Kedrion Biopharma Inc; Fort Lee, NJ. Revised 09/2013. Available at: http://www.gammaked.com/ . Accessed June 8, 2016.

George JN, Knudtson EJ. Thrombocytopenia in pregnancy. 11/13/15. Available at:
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Gilardin L, Bayry J, Kaveri SV. Intravenous immunoglobulin as clinical immune-modulating therapy. CMAJ. 2015;187(4):257-64. Epub 2015 Feb 9.

Gilhus NE, Verschuuren JJ. Myasthenia gravis: subgroup classification and therapeutic strategies. Lancet Neurol. 2015;14(10):1023-36. Review.

Gold R, Hohlfeld R, Toyka KV. Progress in the treatment of myasthenia gravis. Therapeutic Advances in Neurological Disorders. 2008;1(2):36–51.

Gray O, McDonnell GV, Forbes RB. Intravenous immunoglobulins for multiple sclerosis. Cochrane Database of Systematic Reviews 2003;3:CD002936.

Gürcan HM, Jeph S, Ahmed AR. Intravenous immunoglobulin therapy in autoimmune mucocutaneous blistering diseases a review of the evidence for its efficacy and safety. Am J Clin Dermatol. 2010;11(5) 315-26.

Hammerman C, Kaplan M, Vreman HJ, Stevenson DK. Intravenous immune globulin in neonatal ABO isoimmunization factors associated with clinical efficacy. Biol Neonate. 1996;70(2) 69-74.

Hartung HP, Mouthon L, Ahmed R, et al. Clinical applications of intravenous immunoglobulins (IVIg)--beyond immunodeficiencies and neurology. Clin Exp Immunol. 2009 Dec;158 Suppl 1:23-33.

Hizentra package insert. Bern, Switzerland: CSL Behring AG. 01/2015. Available at:
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Hostoffer RW. Selective IgA deficiency: Management and prognosis. 08/31/2015. Available at:
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Howell JE, Gulbis AM, Champlin RE, Qazilbash MH. Retrospective analysis of weekly intravenous immunoglobulin prophylaxis versus intravenous immunoglobulin by IgG level monitoring in hematopoietic stem cell transplant recipients. Am J Hematol. 2011[Epub ahead of print].

Huang Y-C, Li Y-C, Chen T-J. The efficacy of intravenous immunoglobulin for the treatment of toxic epidermal necrolysis: a systematic review and meta-analysis. Br J Dermatol. 2012;167:424-432.

Hughes RA, Dalakas MC, Cornblath DR, Latov N, Weksler ME, Relkin N. Clinical applications of intravenous immunoglobulins in neurology. Clin Exp Immunol. 2009 Dec;158 Suppl 1:34-42.

Hughes RA, Swan AV, van Doorn PA. Intravenous immunoglobulin for Guillain-Barré syndrome. Cochrane Database Syst Rev. 2014 Sep 19;9:CD002063. [Epub ahead of print].

Huizing K, Røislien J, Hansen T. Intravenous immune globulin reduces the need for exchange transfusions in Rhesus and AB0 incompatibility. Acta Paediatr. 2008;97(10) 1362-5. Epub 2008 Jul 9.

HyQvia. package insert. Baxter Healthcare Corporation: Westlake Village, CA. 02/2016. Available at: http://www.hyqvia.com/ . Accessed June 1, 2016.

Immune Deficiency Foundation. About primary immunodeficiencies: specific disease types. 2013. Available at: http://primaryimmune.org/about-primary-immunodeficiencies/specific-disease-types/ . Accessed August 9, 2016.

Jayne DR, Chapel H, Adu D, et al. Intravenous immunoglobulin for ANCA-associated systemic vasculitis with persistent disease activity. QJM. 2000;93(7):433-439.

Jolles S, Sewell WA, Misbah SA. Clinical uses of intravenous immunoglobulin. Clin Exp Immunol. 2005;142(1):1-11.

Karceski S. Neuromyelitis Optica. Neurology. 2009;72 e40-e41.

King TE. Treatment and prognosis of eosinophilic granulomatosis with polyangiitis (Churg-Strauss). July 2016. Available at: http://www.uptodate.com/contents/treatment-and-prognosis-of-churg-strauss-syndrome-allergic-granulomatosis-and-angiitis?source=search_result&search=churg+strauss+vasculitis&selectedTitle=2%7E150 [via subscription only]. Accessed July 19, 2016.

Knutsen AP. IgG subclass deficiency. Updated 11/13/15. Available at:
http://www.uptodate.com/contents/igg-subclass-deficiency [via subscription only]. Accessed August 1, 2016.

Letsky EA, Greaves M. Guidelines on the Investigation and Management of Thrombocytopenia in Pregnancy and Neonatal Alloimmune Thrombocytopenia. Br J Haematol. 1996;95(1).

Lexi-Drugs Compendium. Immune Globulin. [Lexicomp Online Web site]. 06/13/16. Available at: http://online.lexi.com/lco/action/home [via subscription only]. Accessed June 13, 2016.

Lopriore E, Mearin ML, Oepkes D, et al. Neonatal hemochromatosis: management, outcome, and prevention. Prenat Diagn. 2013;33(13):1221-5. Epub 2013 Oct 4.

Lotze TE, Chadwick DJ. Acute disseminated encephalomyelitis in children: Treatment and prognosis. 03/2016. Available at: https://www.uptodate.com/contents/acute-disseminated-encephalomyelitis-in-children-treatment-and-prognosis [via subscription only]. Accessed August 1, 2016.

Magraner MJ, Coret F, Casanova B. The effect of intravenous immunoglobulin on neuromyelitis optica. Neurologia. 2013;28(2):65-72. Epub 2012 Jul 28.

Mayo Clinic. Disease and Conditions: neuromyelitis optica. 09/19/15. Available at: http://www.mayoclinic.org/neuromyelitis-optica/ . Accessed August 10, 2016.

Medscape: Management of Myasthenia Gravis. Semin Neurol. 2004;24(1).

Merck Manual. Eosinophilic Disorders. 2016. Available at: http://www.merckmanuals.com/home/blood-disorders/white-blood-cell-disorders/eosinophilic-disorders . Accessed December 8, 2016.

Merck Manual. Hyper-IgE Syndrome. Updated 08/2016. Available at: http://www.merckmanuals.com/professional/immunology-allergic-disorders/immunodeficiency-disorders/hyper-ige-syndrome . Accessed December 8, 2016.

Merck Manual. Immunodeficiency disorders. Updated 11/2013. Available at: http://www.merckmanuals.com/professional/immunology_allergic_disorders/immunodeficiency_disorders/overview_of_immunodeficiency_disorders.html . Accessed August 9, 2016.

Mir MA. Immune thrombocytopenia and pregnancy: Treatment & management and medication. Updated 10/09/2015. Available at: http://emedicine.medscape.com/article/208697-treatment and
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Mofenson LM, Brady MT, Danner SP, et al. Guidelines for the prevention and treatment of opportunistic infections among HIV-Exposed and HIV-Infected children (Recommendations from CDC, the National Institutes of Health, the HIV Medicine Association of the Infectious Diseases Society of America, the Pediatric Infectious Diseases Society, and the American Academy of Pediatrics). Updated 8/25/2009. Morbidity and Mortality Weekly Report. August 26, 2009 / 58(Early Release);1-166.

Multiple Sclerosis Therapy Consensus Group (MSTCG), Wiendl H, Toyka KV, Rieckmann P, Gold R, Hartung HP, Hohlfeld R. Basic and escalating immunomodulatory treatments in multiple sclerosis current therapeutic recommendations. J Neurol. 2008 Oct;255(10) 1449-63. doi 10.1007/s00415-008-0061-1. Epub 2008 Oct 29.

Neunert C, Lim W, Crowther M, et al; American Society of Hematology. The American Society of Hematology 2011 evidence-based practice guideline for immune thrombocytopenia. Blood. 2011;117(16) 4190-207.

NHIC, Corp. Local Coverage Article.Intravenous immune globulin. Policy Article A52509. [NHIC Web site]. Original 10/01/2015. Available at:
https://www.cms.gov/medicare-coverage-database/details/article-details.aspx?articleId=52509&ver=3&ContrId=137&ContrVer=1&LCDId=33610&CntrctrSelected=137*1&Cntrctr=137&DocType=Future&IsPopup=y& . Accessed June 1, 2016.

NHIC, Corp. Local Coverage Determination (LCD and Policy Article). L33794 & A52507 External infusion pumps. [NHIC Web site]. Original 10/01/2015, Revised 01/01/2016. Available at: http://www.medicarenhic.com/viewdoc.aspx?id=3337 . Accessed June 1, 2016.

NHIC, Corp. Local Coverage Determination (LCD). L33610 LCD for intravenous immune globulin. [NHIC Web site]. Original 10/01/15. Available at: https://www.cms.gov/medicare-coverage-database/details/lcd-details.aspx?LCDId=33610&ContrId=137&ver=4&ContrVer=1&CntrctrSelected=137*1&Cntrctr=137&DocType=Future&bc=AAAAAAIAAAAAAA%3d%3d&. Accessed June 1, 2016.

NINDS Neuromyelitis Optica Information Page. National Institute of Neurological Disorders and Stroke. 02/23/16. Available at: http://www.ninds.nih.gov/disorders/neuromyelitis_optica/neuromyelitis_optica.htm . Accessed August 10, 2016.

Noridian Healthcare Solutions. Local Coverage Determination (LCD and Policy Article). L33794 & A52507. External infusion pumps. Original 10/01/2015, Revised 01/01/2016. Available at: https://med.noridianmedicare.com/web/jadme/policies/lcd/active . Accessed August 1, 2016.

Noridian Healthcare Solutions. Local Coverage Determination (LCD and Policy Article). L33610 & A52509. Intravenous Immune Globulin. Original 10/01/2015. Available at: https://med.noridianmedicare.com/web/jadme/policies/lcd/active . Accessed August 1, 2016.

Novitas Solutions, Inc. Local Coverage Determination (LCD)L35093 - Intravenous Immune Globulin (IVIG). [Novitas Solutions Web site]. Original 10/01/2015, Revised 01/01/16. Available at: https://www.cms.gov/medicare-coverage-database/details/lcd-details.aspx?LCDId=35093&ContrId=323&ver=41&ContrVer=1&CntrctrSelected=323*1&Cntrctr=323&DocType=Active&bc=AgACAAIAAAAAAA%3d%3d& . Accessed August 8, 2016.

Okada K, Tsuji S, Tanaka K. Intermittent intravenous immunoglobulin successfully prevents relapses of neuromyelitis optica. Intern Med. 2007;46 1671-1672.

Olek MJ. Diagnosis of multiple sclerosis in adults. 02/22/16. UpToDate Website Available at: http://www.uptodate.com/contents/diagnosis-of-multiple-sclerosis-in-adults?source=search_result&search=neuromyelitis+optica+adult&selectedTitle=1%7E13 . Accessed August 10, 2016.

Orange JS. Immune globulin therapy in primary immunodeficiency. 11/13/2015. Available at: https://www.uptodate.com/contents/immune-globulin-therapy-in-primary-immunodeficiency?source=search_result&search=immune%20globulin%20therapy%20in%20primary&selectedTitle=1~150 . Accessed October 24, 2016.

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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.

Patwa HS, Chaudhry V, Katzberg H, et al. Evidence-based guideline: intravenous immunoglobulin in the treatment of neuromuscular disorders report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology. Neurology 2012 Mar 27;78(13) 1009-15.

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Routes JM. Pulmonary Complications of Primary Immunodeficiencies. In Mason RJ, Broaddus VC, Martin TR, King TE Jr, Schraufnagel DE, Murray JF, Nadel JA, eds. Murray and Nadel's Textbook of Respiratory Medicine, 5th edition. Philadelphia, PA: Saunders/Elsevier 2010.

Schrier SL. Warm autoimmune hemolytic anemia: Treatment. UpToDate Website. March 2016. Available at:https://www.uptodate.com/contents/warm-autoimmune-hemolytic-anemia-treatment?source=see_link&sectionName=INTRAVENOUS+GAMMA+GLOBULIN&anchor=H14#H14 . Accessed July 15, 2016.

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Segura S, Iranzo P, Martínez-de Pablo I, et al. High-dose intravenous immunoglobulins for the treatment of autoimmune mucocutaneous blistering diseases evaluation of its use in 19 cases. J Am Acad Dermatol. 2007;56(6) 960-7.

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Sinha AA, Hoffman MB, Janicke EC. Pemphigus vulgaris: approach to treatment. Eur J Dermatol. 2015;25(2):103-13.

Sorensen RU, Paris K. Selective antibody deficiency with normal immunoglobulins. Updated 11/26/2013. Available at: http://www.uptodate.com/contents/selective-antibody-deficiency-with-normal-immunoglobulins [via subscription only]. Accessed August 9, 2016.

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Sakthiswary R, D'Cruz D. Intravenous immunoglobulin in the therapeutic armamentarium of systemic lupus erythematosus: a systematic review and meta-analysis. Medicine (Baltimore). 2014;93(16):e86.

The Asthma Center. Disease information recurrent Infection - primary immunodeficiency. 2016. Available at: http://www.theasthmacenter.org/index.php/disease_information/recurrent_infection/ . Accessed August 9, 2016.

Tramacere I, Del Giovane C, Salanti G, et al. Immunomodulators and immunosuppressants for relapsing-remitting multiple sclerosis: a network meta-analysis. Cochrane Database Syst Rev. 2015;(9):CD011381.

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Truven Health Analytics Inc. Micromedex® Solutions. DrugDex®. [Internet database]. Immune Globulin. 06/02/16. Available at:
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REFERENCES FOR EXPERIMENTAL/INVESTIGATIONAL INDICATIONS

Alzheimer's Disease

Dodel R, Neff F, Noelker C, et al. Intravenous immunoglobulins as a treatment for Alzheimer's disease rationale and current evidence. Drugs. 2010;70(5) 513-28.

Dodel R, Rominger A, Bartenstein P, et al. Intravenous immunoglobulin for treatment of mild-to-moderate Alzheimer's disease: a phase 2, randomised, double-blind, placebo-controlled, dose-finding trial. Lancet Neurol. 2013 Mar;12(3):233-43.

Puli L, Tanila H, Relkin N. Intravenous immunoglobulins for Alzheimer's disease. Curr Alzheimer Res. 2014;11(7):626-36.

Relkin N. Intravenous immunoglobulin for Alzheimer's disease. Clin Exp Immunol. 2014 Dec;178 Suppl 1:27-9.

Relkin N, on behalf of the GAP Study Group. Results of GAP (160701): a Phase III study of intravenous gammaglobulin for the treatment of mild to moderate Alzheimer’s disease. Presented at AAIC, Boston 2013.

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.

Autism

DelGiudice-Asch G, Simon L, Schmeidler J, et al. J Autism Dev Disord. 1999;29 157-160.

Feasby T, Banwell B, Benstead T, et al. Guidelines on the use of intravenous immune globulin for neurologic conditions. Transfus Med Rev. 2007;21(Suppl 1) S57-S107.

Gupta S. Treatment of children with autism with intravenous immunoglobulin. J Child Neurol. 1999;14 203-205.

Kidd PM. Autism, an extreme challenge to integrative medicine. Part 2 medical management. Altern Med Rev. 2002;7 472-499.

Krause I, He XS, Gershwin ME, et al. Brief report immune factors in autism a critical review. J Autism Dev Discord. 2002;32 337-345.

Lai MC, Lombardo MV, Baron-Cohen S. Autism. Lancet. 2014;383(9920):896-910. Epub 2013 Sep 26.

Plioplys AV. Intravenous immunoglobulin treatment of children with autism. J Child Neurol. 1998;13 79-82.

Plioplys AV. Response to the letter by Dr Gupta concerning the treatment of autistic children with intravenous immunoglobulin. J Child Neurol. 1999;14 203-205.

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.

Weissman L, Bridgemohan C. Autism spectrum disorders in children and adolescents Complementary and alternative therapies. 10/05/15. 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 August 9, 2016.

Whitehouse AJ. Complementary and alternative medicine for autism spectrum disorders: rationale, safety and efficacy. J Paediatr Child Health. 2013 Sep;49(9):E438-42:quiz E442. Epub 2013 May 20.

Autoimmune Encephalopathy

Byun JI, Lee ST, Jung KH, et al. Effect of Immunotherapy on Seizure Outcome in Patients with Autoimmune Encephalitis: A Prospective Observational Registry Study. PLoS One. 2016;11(1):e0146455.

Caselli RJ, Drazkowski JF, Wingerchuk DM. Autoimmune encephalopathy. Mayo Clin Proc. 2010;85(10):878-80.

Dalmau J, Rosenfeld MR, et al. Paraneoplastic and autoimmune encephalitis. UpToDate Website. 04/06/16. Available at: http://www.uptodate.com/contents/paraneoplastic-and-autoimmune-encephalitis?source=search_result&search=paraneoplastic+limbic+encephalitis&selectedTitle=1%7E2#H2380193 . Accessed August 10, 2016.

Flanagan EP, Caselli RJ. Autoimmune encephalopathy. Semin Neurol. 2011;31 144-157.

Gastaldi M, Thouin A, Vincent A. Antibody-Mediated Autoimmune Encephalopathies and Immunotherapies. Neurotherapeutics. 2016;13(1):147-62.

Lancaster E. The Diagnosis and Treatment of Autoimmune Encephalitis. J Clin Neurol. 2016;12(1):1-13.

Nanri K, Okuma M, Sato S, et al. Prevalence of Autoantibodies and the Efficacy of Immunotherapy for Autoimmune Cerebellar Ataxia. Intern Med. 2016;55(5):449-54. Epub 2016 Mar 1.

Nosadini M, Mohammad SS, Ramanathan S, Brilot F, Dale RC. Immune therapy in autoimmune encephalitis: a systematic review. Expert Rev Neurother. 2015;15(12):1391-419. Epub 2015 Nov 24.

Suthar R, Saini AG, Sankhyan N, Sahu JK, Singhi P. Childhood Anti-NMDA Receptor Encephalitis. Indian J Pediatr. 2016 Jul;83(7):628-33. Epub 2016 Jan 23.

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. 04/06/16. Available at: http://www.uptodate.com/contents/paraneoplastic-and-autoimmune-encephalitis?source=search_result&search=paraneoplastic+limbic+encephalitis&selectedTitle=1%7E2#H2380193 . Accessed August 10, 2016.

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

Grisold W, Giometto B, Vitaliani R, et al. Current approaches to the treatment of paraneoplastic encephalitis. Ther Adv Neurol Disord. 2011;4 237-248.

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.

Uchuya M, Graus F, Verg F, et al. Intravenous immunoglobulin treatment in paraneoplastic neurological syndromes with antineuronal autoantibodies. J Neurol Neurosurg Psychiatry. 1996;60 388-392.

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 August 10, 2016.

Clinical Trials.Gov. Intravenous immunoglobulin for PANDAS (Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections. Available at: http://clinicaltrials.gov/ct2/show/NCT01281969 . Accessed August 10, 2016.

Farhood Z, Ong AA, Discolo CM. PANDAS: A systematic review of treatment options. Int J Pediatr Otorhinolaryngol. 2016;89:149-53. Epub 2016 Aug 12.

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.

Gilbert DL, Kurlan R. PANDAS: horse or zebra? Neurology. 2009;73(16):1252-3. Epub 2009 Sep 30.

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.

Kurlan R, Kaplan EL. The pediatric autoimmune neuropsychiatric disorder associated with streptococcal infection (PANDAS) etiology for tics and obsessive-compulsive symptoms Hypothesis or entity? Practical considerations for the clinician. Pediatrics. 2004;113 883-886.

Lechman JF, King RA, Gilbert DL, et al. Streptococcal upper respiratory tract infections and exacerbations of tic and obsessive-compulsive symptoms A prospective longitudinal study. J Am Acad Child Adolesc Psychiatry. 2011;50 108-118.

Leonard HL, Swedo SE. Paediatric autoimmune neuropsychiatric disorders associated with streptococcal infection (PANDAS). Int J Neuropsychopharmacol. 2001;4 191-198.

Lewin AB, Storch EA, Murphy TK. Pediatric autoimmune neuropsychiatric disorders associated with Streptococcus in identical siblings. J Child Adolesc Psychopharmacol. 2011;21(2):177-82. Epub 2011 Apr 12.

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. doi: 10.1089/cap.2014.0067. Epub 2015 Feb 6.

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.

Martino D, Defazio G, Giovannoni G. The PANDAS subgroup of tic disorders and childhood-onset obsessive-compulsive disorder. J Psychosom Res. 2009;67 547-557

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.

Murphy TK, Gerardi DM, Leckman JF. Pediatric acute-onset neuropsychiatric syndrome. Psychiatr Clin North Am. 2014;37(3):353-74. Review.

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. 04/2016. Available at: https://www.nimh.nih.gov/labs-at-nimh/research-areas/clinics-and-labs/pdnb/pandas-frequently-asked-questions.shtml . Accessed October 6, 2016.

Nicolson R, Swedo SE, Lenane M, et al. An open trial of plasma exchange in childhood-onset obsessive-compulsive disorder without poststreptococcal exacerbations. J Am Acad Child Adolesc Psychiatry. 2000; 39:1313.

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. Updated 03/15/16. Available at: http://www.uptodate.com/contents/pandas-pediatric-autoimmune-neuropsychiatric-disorder-associated-with-group-a-streptococci?topicKey=PEDS%2F6031&elapsedTimeMs=14&source=search_result&searchTerm=pandas&selectedTitle=1%7E9&view=print&displayedView=full# . Accessed August 10, 2016.

Practice parameter for the assessment and treatment of children and adolescents with obsessive-compulsive disorder. J Am Acad Child Adolesc Psychiatry. 2012 Jan;51(1):98-113.

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. Epub 2016 Aug 3.

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.

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

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 August 10, 2016.

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 12/02/15. Available at: http://www.ninds.nih.gov/disorders/postural_tachycardia_syndrome/postural_tachycardia_syndrome.htm . Accessed August 10, 2016.

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.

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 Organization of Rare Diseases. Yellow nail syndrome. 2012.

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)

90283, 90284


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

J1575 Injection, immune globulin/hyaluronidase, 100 mg immuneglobulin


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


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 08.00.13t
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: 01/01/2018
Version Issued Date: 12/29/2017
Version Reissued Date: N/A

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