This policy is designed to address medical guidelines that are appropriate for the majority of individuals with a particular disease, illness, or condition. Each person's unique clinical circumstances may warrant individual consideration, based on review of applicable medical records.
Subcutaneous Immune Globulin (SCIG) Therapy
Subcutaneous Immune Globulin may be considered medically necessary for the treatment of primary immunodeficiencies when ALL of the following criteria are met:
- 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
o 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 4-fold increase in titers for at least 50% of serotypes tested; or
o 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 4-fold rise in titers 3-4 weeks after vaccine administration; and
- Other unspecified disorder of immune mechanism may be given individual consideration.
Primary immunodeficiencies also include:
- Congenital agammaglobulinemia; or
- Hypogammaglobulinemia; or
- Common variable immunodeficiency (CVID); or
- Severe combined immunodeficiency; or
- Wiskott-Aldrich syndrome; or
- X-linked agammaglobulinemia (XLA).
Other applications of SCIg therapy are considered experimental/investigational, including, but not limited to chronic inflammatory demyelinating polyneuropathy (CIDP) because their safety and/or effectiveness cannot be established by review of the published peer-reviewed literature
Intravenous Immune Globulin (IVIG) Therapy
Intravenous immune globulin ( IVIG) may be considered medically necessary for treatment of ANY ONE of the following conditions when standard therapies have failed, become intolerable, or are contraindicated:
Acute Humoral Rejection; or
Autoimmune Mucocutaneous Blistering Disease used for short term therapy not maintenance therapy
- Autoimmune mucocutaneous blistering disease for the following biopsy-proven conditions: pemphigus vulgaris, pemphigus foliaceus, bullous pemphigoid, mucous membrane pemphigoid (cicatricial pemphigoid), epidermolysis bullosa acquisita, Stevens-Johnson syndrome and toxic epidermal necrolysis (TEN) when ANY ONE of the following criteria is met:
- The individual failed conventional therapy (eg, steroids, methotrexate, immunosuppressive therapy) or conventional therapy is contraindicated; or
- The individual has a rapidly progressive disease in which a clinical response could not be affected 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; or
Autoimmune and inflammatory disorders
- Dermatomyositis refractory to treatment with corticosteroids; in combination with other immunosuppressive agents; or
- Kawasaki disease (mucocutaneous lymph node syndrome); or
Hematologic
- Idiopathic thrombocytopenia purpura (ITP)
- Treatment of acute, severe ITP defined by ANY ONE of the following parameters:
- Acute ITP with major bleeding, e.g., life-threatening bleeding and/or clinically important mucocutaneous bleeding; or
- Acute ITP with severe thrombocytopenia and at high risk for bleeding complications; or
- Acute ITP with severe thrombocytopenia and a slow or inadequate response to corticosteroids; or
- Acute ITP with 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 patients 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 immunosuppressive agents; 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 patients; or
- Patients with primary defective antibody synthesis; or
Neuroimmunological
- Myasthenia gravis chronic, severe, refractory to standard therapy (i.e., interferons, steroids/myasthenia crisis); or
- Guillain Barre syndrome (acute infective polyneuritis); or
- 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 sensory, rarely only motor 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. This will usually involve all four (4) limbs; and
- Nerve conduction studies including studies of proximal nerve segments in which the predominant process is demylination. (Must have 3 of the following):
- Reduction in conduction velocity (CV) in two (2) or more motor nerves:
- Less than 80% of lower limit of normal (LLN) is amplitude greater than 80% of LLN; and
- Less than 70% of LLN is amplitude less than 80% of LLN; or
- Partial conduction block or abnormal temporal dispersion and possible conduction block one (1) or more motor nerves:
Partial conduction block:
- Less than 15% change in duration between proximal an distal sites; and
- Greater than 20% drop in negative peak (p) area or peak to peak (p-p) amplitude between proximal and distal sites.
OR
- Abnormal temporal dispersion and possible conduction block:
- Less than 15% change in duration between proximal and distal sites; and
- Greater than 20% drop in p area or p-p amplitude between proximal and distal sites; and
- Greater than 20% drop in p or p-p amplitude between proximal and distal sites; or
- Prolonged distal latencies in two (2) or more nerves:
- Greater than 125% of upper limit of normal (LEN) if compound muscle action potential (CMAP) amplitude greater than 80% of LLN; and
- Greater than 150% of LEN if CMAP amplitude less than 80% of LLN; or
- Absent F waves or prolonged minimum
- Greater than 120% of ULN if CMAP amplitude greater than 80% of LLN; and
- Greater than 150% of ULN if CMAP amplitude less than 80% of LLN; and
- Pathological findings are tested using the following:
- Nerve biopsy showing unequivocal evidence of demyelination and remyelination; and
- Demyelination by either electron microscopy (more than 5 fibers) or teased fiber studies more than 12% of 50 fibers, minimum of 4 internodes each, demonstrating demyelination/remyelination; and
- Cerebrospinal fluid studies (CSF) studies include the following tests:
- Cell count less than 10 per cubic mm if HIV-seronegative or less than 50 per cubic mm is HIV seropositive; and
- Negative Venereal Disease Research Laboratory test (VDRL); or
- Multifocal motor neuropathy in patients with anti GM1 antibodies and conduction block; 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 patient’s clinical status from the visit prior to the one prompting the decision to initiate immune globulin therapy; or
Primary immune deficiency syndromes, including combined immunodeficiencies
- Treatment of primary immunodeficiencies, including congenital agammaglobulinemia (total IgG less than 200 mg/dl); or
- Common variable immunodeficiency (hypogammaglobulinemia (total IgG less than 400 mg/dl or at least 2 standard deviations below normal, on at least 2 occasions)); or
- Severe combined immunodeficiency; or
- Wiskott-Aldrich syndrome; or
- X-linked agammaglobulinemia (total IgG less than 200 mg/dl); or
- X-linked Hyper-IgM Syndrome; or
- Ataxia telangiectasia; or
Individuals with primary immunodeficiency syndromes should meet ALL of the following criteria for treatment with IVIG:
- 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 EITHER of the following:
- 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 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 4-fold rise in titers 3-4 weeks after vaccine administration; and
- Other unspecified disorder of immune mechanism may be given individual consideration; or
Transplantation
- Prior to solid organ transplant, for treatment of patients at high risk of antibody-mediated rejection (AMR) after steroid or other immunosuppressant failure, including highly sensitized patients, and those receiving an ABO incompatible organ; or
- Following solid organ transplant, for treatment of AMR.
The use of IVIG for any other indication is considered experimental/investigational and therefore non-covered. Scientific evidence does not support of the use of any other indications than those listed above.
Preferred Product(s)
Gamunex/Gamunex-C (Immune Globulin Intravenous [Human]
Non-Preferred Product(s)
In order for a request for a non-preferred immune globulin product to be approved, ANY ONE of the following must be met:
- The individual must have had an adequate therapeutic trial* and experienced a documented drug therapy failure** with the preferred IG product(s); or
- The individual is being treated with a non-preferred IG product for an indication for which the non-preferred product is FDA-approved and the preferred product(s) is/are not FDA-approved; or
- The individual is currently stable on a non-preferred IG product in such cases where the member has previously experienced an intolerable adverse effect with another non-preferred IG product and a change to a preferred IG product would be likely to cause the same intolerable adverse effect due to similarities in individual product characteristics (e.g. IgA content, sugar content, sodium content, concentration); or
- The individual is therapy naïve, but whose clinical characteristics, as documented by objective laboratory evidence (i.e. IgA level), would predispose them to significant adverse events associated with the use of a preferred product; or
- The individual is less than 18 years of age and is currently stable on a non-preferred product. Individuals less than 18 years of age who are new to therapy will be required to start on a preferred IG product unless criteria 2 or 4 are met above.
In the event that the preferred IG product(s) is/are not available due to a product shortage, authorization of non-preferred products will be provided to members who require continued therapy.
Experimental/Investigational (E/I) services are not covered regardless of place of service.
Evidence based guidelines support the administration of this drug in alternative sites of care such as the home or outpatient infusion centers. Administration of infusible drugs at alternate sites of care is based upon the professional judgment of the provider, and take into account the clinical appropriateness for each individual patient.
Services that do not meet the criteria of this policy will be considered experimental/investigational (E/I). A network provider can bill the member for the experimental/investigational service. The provider must give advance written notice informing the member that the service has been deemed E/I. The member must be provided with an estimate of the cost and the member must agree in writing to assume financial responsibility in advance of receiving the service. The signed agreement must be maintained in the provider’s records.
