Immune globulin is one of five closely-related proteins found in the human body. These proteins are capable of acting as antibodies. Gamma globulin is an intravenous, subcutaneous or intramuscular drug which has IgG antibodies and is used for the prevention and treatment of specific disease.

Subcutaneous Immune Globulin (SCIG) Therapy

Primary Immunodeficiencies

Subcutaneous Immune Globulin (Cutaquig, Cuvitru, Gammagard Liquid, Gammaked, Gamunex-C, Hizentra, HyQvia, or Xembify) may be considered medically necessary when ALL of the following criteria are met:

• Individual diagnosed with primary immunodeficiencies [e.g., congenital agammaglobulinemia, hypogammaglobulinemia, common variable immunodeficiency (CVID), severe combined immunodeficiency, Wiskott-Aldrich syndrome, or X-linked agammaglobulinemia (XLA)]; and
• Standard therapies have failed, become intolerable, or are contraindicated; and
• Laboratory evidence of immunoglobulin deficiency; and   
• Persistent and severe infections despite treatment with prophylactic antibiotics; and
• Documented inability to mount an adequate immunologic response to inciting antigens; and
  • Lack of appropriate rise in antibody titer following provocation with a polysaccharide antigen. For example, an adequate response to the pneumococcal vaccine may be defined as at least a four (4)-fold increase in titers for at least 50% of serotypes tested; or
  • Lack of appropriate rise in antibody titer following provocation with a protein antigen. For example, an adequate response to tetanus/diphtheria vaccine may be defined as less than a four (4)-fold rise in titers three (3)-four (4) weeks after vaccine administration; and
• Other unspecified disorder of immune mechanism may be given individual consideration; and
• Initial authorization will be for a period of 12 months.

Chronic Inflammatory Demyelinating Polyneuropathy (CIDP)

Subcutaneous Immune Globulin (Cutaquig, Cuvitru, Gammagard Liquid, Gammaked, Gamunex-C, Hizentra, HyQvia, or Xembify ) may be considered medically necessary for individuals 18 years of age or older when ALL of the following criteria are met:

• Individual has confirmed diagnosis of CIDP; and
• Individual has demonstrated clinically meaningful response as indicated by documentation of stable or improved symptoms on intravenous immune globulin (IVIG) therapy; and
• Initial authorization will be for a period of 12 months.

Reauthorization Criteria

Continuation of SCIG (Cutaquig, Cuvitru, Gammagard Liquid, Gammaked, Gamunex-C, Hizentra, HyQvia, or Xembify) may be considered medically necessary when ALL of the following criteria are met:

• Individual has one of the diagnoses above; and
• Individual has demonstrated clinically meaningful response as indicated by documentation of stable or improved symptoms; and
• Reauthorization will be for a period of 12 months.

The use of SCIG therapy not meeting the criteria as indicated in this policy is considered not medically necessary.

Intravenous Immune Globulin (IVIG) Therapy

IVIG (Asceniv, Bivigam, Flebogamma DIF, Gammagard Liquid, Gammagard S/D, Gammaked, Gammaplex, Gamunex-C, Octagam, Panzyga, and Privigen) may be considered medically necessary for treatment of ANY ONE of the following conditions when standard therapies have failed, become intolerable, or are contraindicated:

Autoimmune and Inflammatory Disorders

• Autoimmune mucocutaneous blistering disease which is severe and progressive including pemphigus, pemphigoid, pemphigus vulgaris, pemphigus foliaceus, bullous pemphigoid, mucous membrane pemphigoid, epidermolysis bullosa acquisita, Stevens-Johnson syndrome and toxic epidermal necrolysis (TEN) when individual has failed treatment with conventional agents such as corticosteroids, azathioprine, and cyclophosphamide; or
• Dermatomyositis or polymyositis refractory to treatment with corticosteroids; in combination with other immunosuppressive agents; or
• Kawasaki disease (mucocutaneous lymph node syndrome); or
• Wegener’s granulomatosis; or
• Neuromyelitis optica as an alternative for those with contraindications or lack of response to first-line treatment; and
• Initial authorization will be for a period of 12 months.

Hematologic

• Idiopathic thrombocytopenia purpura (ITP):
  • Diagnosis of acute, severe ITP; and
  • Alternate etiologies of thrombocytopenia have been ruled out; and
  • Individual has one of the following:
    • Major bleeding (e.g., life-threatening bleeding and/or clinically important mucocutaneous bleeding); or
    • Severe thrombocytopenia and is at high risk for bleeding complications; or
    • Severe thrombocytopenia and a slow or inadequate response to corticosteroids; or
    • Severe thrombocytopenia and a predictable risk of bleeding in the future (e.g., a procedure or surgery with a high bleeding risk); or
  • Treatment of chronic ITP in individuals with BOTH of the following:
    • Duration of disease has been at least six (6) months; and
    • Individual has persistent thrombocytopenia despite treatment with corticosteroids and splenectomy; or
• Fetal/neonatal alloimmune thrombocytopenia; or
• Hemolytic disease of the fetus and newborn (e.g. erythroblastosis fetalis); or
• Post allogeneic bone marrow transplant setting; or
• Individuals with hypogammaglobulinemia and/or recurrent bacterial infections associated with B-cell chronic lymphocytic leukemia, multiple myeloma or post-transplant lymphoproliferative disorder (PLD); or
• Warm antibody autoimmune hemolytic anemia, refractory to corticosteroids and splenectomy; or
• Antiphospholipid syndrome; or
• Severe anemia due to parvovirus B19; or

Infectious Disease

• Prevention of infection in EITHER of the following:
  • Prevention of infection in pre-term (less than 37 weeks gestational age) and/or low birth weight (less than 2500g) neonates; or 
  • Neonates predisposed to group B streptococcal infections; or
• Toxic shock syndrome caused by staphylococcal or streptococcal organisms refractory to conventional therapy; or
• HIV infected individuals; or
• Individuals with primary defective antibody synthesis; or

Neuroimmunological

• Chronic inflammatory demyelinating polyneuropathy (CIDP) in individuals with progressive symptoms for at least two (2) months when ALL of the following criteria are met:
  • Progressive or relapsing motor and/or sensory dysfunction of more than one (1)  limb or a peripheral nerve nature, developing over at least two (2)  months; and
  • Hypo- or areflexia (usually involving all four (4) limbs); and
  • Nerve conduction studies strongly supportive of demyelination with at least ONE of the following (consistent with EFNS/PNS guidelines further defined in Professional Statements and Societal Positions section below :
    • Motor distal latency prolongation in at least two (2) nerves; or
    • Reduction of motor conduction velocity in at least two (2) nerves; or
    • Prolongation of F-wave latency in at least two (2) nerves; or
    • Absence of F-waves in at least two (2) nerves; or
    • Motor conduction block in at least one (1) nerve; or
    • Abnormal temporal dispersion in at least two (2) nerves; or
    • Distal CMAP duration prolongation in at least one (1) nerve; or
• Multifocal motor neuropathy in patients with anti GM1 antibodies or conduction block; or
• Myasthenia gravis chronic, severe, refractory to standard therapy (i.e., azathioprine, steroids); or
• Guillain Barre syndrome (acute infective polyneuritis); or
• Myasthenic crisis; or
• Lambert-Eaton myasthenic syndrome when there is failure, contraindication, or intolerance to other therapies (i.e. anticholinesterase and diaminopyridine); or
• Relapsing-remitting multiple sclerosis (RRMS) when ALL the following criteria are met:
  • Other therapy (e.g., interferon beta, glatiramer) has failed, become intolerable, and/or is contraindicated; and
  • 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; and
  • Documentation of an MS exacerbation or progression (worsening) of the individual’s clinical status from the visit prior to the one prompting the decision to initiate immune globulin therapy; or
• Stiff person syndrome not controlled by at least one (1) other therapy; or

Primary immune deficiency syndromes, including combined immunodeficiencies

• Individual diagnosed with primary immunodeficiencies [e.g., congenital agammaglobulinemia (total IgG less than 200mg/dl), hypogammaglobulinemia, common variable immunodeficiency (CVID), severe combined immunodeficiency, Wiskott-Aldrich syndrome, or X-linked agammaglobulinemia (XLA)]; and
• Laboratory evidence of immunoglobulin deficiency; and
• Persistent and severe infections despite treatment with prophylactic antibiotics; and
• Documented inability to mount an adequate immunologic response to inciting antigens; and
• Other unspecified disorder of immune mechanism may be given individual consideration; or

Transplantation

• Prior to solid organ transplant, for treatment of individuals at high risk of antibody-mediated rejection (AMR) after steroid or other immunosuppressant failure, including highly sensitized individuals, and those receiving an ABO incompatible organ; or
• Renal transplantation for prevention or treatment of acute humoral rejection; or
• Following solid organ transplant, for treatment of AMR; and

Initial authorization will be for a period of 12 months for the above diagnoses.

Reauthorization Criteria

Continuation of IVIG (Asceniv, Bivigam, Flebogamma DIF, Gammagard Liquid, Gammagard S/D, Gammaked, Gammaplex, Gamunex-C, Octagam, Panzyga, and Privigen)  may be considered medically necessary when ALL of the following criteria are met:

• Individual has one of the diagnoses above; and
• Inidivual has demonstrated clinically meaningful response as indicated by documentation of stable or improved symptoms; and
• Reauthorization will be for a period of 12 months.

The use of IVIG therapy not meeting the criteria as indicated in this policy is considered not medically necessary.

Intravenous immune globulin therapy may be considered medically necessary for individuals 18 years of age and older when applicable clinical criteria for individual medication policies are met and when administered in a physician’s office not affiliated with a hospital, specialized infusion centers not affiliated with a hospital or in the home.

Outpatient facility (Outpatient Hospital IV Infusion Department or Hospital-based Outpatient Clinical Level of Care) administration may be considered medically necessary if ANY of the following criteria are present to indicate the member is medically unstable for infusions in other than an outpatient facility setting:

• Member’s home is considered unsuitable for care by the home infusion provider; or
• Individual’s medical status requires enhanced monitoring beyond that which would routinely be needed for infusion therapy; or
• Previous severe adverse reaction (including but not limited to anaphylaxis, seizure, thromboembolism, myocardial infarction, renal failure) during or following administration of prescribed medication despite standard pre-medication; or
• Individual is receiving other medications that require close monitoring with a higher level of care (e.g., cytotoxic chemotherapy or blood products); or
• Individual is at high risk for complications due to medication administration (e.g., at risk for post-transplant complications, increased risk of infusion reactions due to presence of circulating antibodies, unstable vascular access, cardiopulmonary condition at risk for severe adverse reactions, unstable renal function with inability to safely tolerate IV volume loads, etc.); or 
• Individual is initiating therapy or re-initiating therapy after a period of at least 6 months with no therapy; or
• Physically and/or cognitively impaired AND a home caregiver is not available to comply with the required treatment regimen and schedule.

Home health services may be considered medically necessary when utilized for the administration of home infusion therapy and when provided by licensed eligible provider. Each case will be addressed on an individual basis.

The medications identified in this policy will be considered not medically necessary if administered in an unapproved hospital outpatient setting when an approved site of care is a viable option for treatment.

NOTE: In addition to the above criteria, product specific dosage and/or frequency limits may apply in accordance with the U.S. Food and Drug Administration (FDA)-approved product prescribing information, national compendia, Centers for Medicare and Medicaid Services (CMS) and other peer reviewed resources or evidence-based guidelines. Highmark may deny, in full or in part, reimbursement for utilization that does not fall within the applicable dosage and/or frequency limits. 

Evidence-based guidelines support the administration of injectable medications in alternative sites of care such as the non-hospital physician’s office, non-hospital infusion center or in the home.  Administration of the injectable medications subject to this policy at alternate sites of care is based upon the professional judgment of the provider, and takes into account the clinical appropriateness for each individual member. Requests for administration of any dose of the drugs listed in this policy received from a hospital-based facility, physician’s office or specialized infusion center will be assessed for meeting the policy exception criteria based on the clinical documentation provided by the requesting practitioner.