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Human immune globulin therapy provides a broad spectrum of opsonizing and neutralizing immunoglobulin G (IgG) antibodies against a wide variety of bacterial and viral antigens. Three formulations of human IgG are available for delivery: by IVIg, SCIg, or by intramuscular (IMIg) depot injections. IMIg has been largely abandoned in the United States because volume constraints and pain preclude delivery of sufficient product weekly into each buttock to yield therapeutic serum levels of IgG, leaving recipients susceptible to infections. Thus, this policy focuses on IVIg and SCIg for conditions that typically would be treated in an outpatient setting.
IVIg immune globulin is an antibody-containing solution obtained from the pooled plasma of healthy blood donors that contains antibodies to greater than 10 million antigens. IVIg has been used to correct immune deficiencies in patients with either inherited or acquired immunodeficiencies and has also been investigated as an immunomodulator in diseases thought to have an autoimmune basis. Several IVIg products are available for clinical use in the United States. The labeled indications approved by the U.S. Food and Drug Administration (FDA) for IVIg are listed in the Policy section. A variety of off-label indications have been investigated; some of the most common are inflammatory myopathies, neuropathies (eg, Guillain-Barré syndrome), myasthenia gravis, multiple sclerosis, and solid organ transplantation.
This policy only addresses nonspecific pooled preparations of IVIg; it does not address other immunoglobulin preparations that are specifically used for passive immunization to prevent or attenuate infection with specific viral diseases such as respiratory syncytial virus, cytomegalovirus, or hepatitis B.
Subcutaneous immune globulin (SCIG) therapy is used for treating patients with primary immunodeficiencies. A genetic basis for more than 80 different types of primary immunodeficiencies has been discovered, the most common being primary antibody deficiency that is associated with low levels or total lack of normal circulating immunoglobulins. With SCIG, it is possible for patients to self-administer the therapy.
Several IVIg products have been approved by FDA. These include Carimune® (ZLB Bioplasma), Flebogamma® (Grifols), Gammagard® (Baxter), Gamunex-C® (Grifols), Octagam® (Octapharma), Polygam® S/D (Baxter) Privigen® (CSL Behring), and BIVIGAM™ (Biotest Pharmaceuticals).
At least one IVIg product is FDA-approved to treat the following conditions:
Several SCIg products have received FDA marketing approval for primary immunodeficiencies. These include Vivaglobin® (ZLB Behring, Kankakee, IL, discontinued by the company in 2013), Hizentra® (ZLB Behring, Kankakee, IL), Gamunex-C® (Grifols), Gammaked® (Kedrion Biopharma, Cambridge, MA), and Hyqvia®.
Prior authorization is required.
Intravenous immune globulin (IVIg) therapy may be considered medically necessary for the following indications:
Primary Humoral Immune Deficiency Syndromes,* Including Combined Immunodeficiencies.
Acute Humoral Rejection
Autoimmune Mucocutaneous Blistering Diseases, in patients with severe, progressive disease, despite treatment with conventional agents (corticosteroids, azathioprine, cyclophosphamide, etc.)
Autoimmune and Inflammatory Disorders
* FDA-labeled indications
IVIg is considered not medically necessary as a treatment of relapsing/remitting multiple sclerosis.
Intravenous immune globulin therapy is considered investigational, including, but not limited to, the following conditions:
Subcutaneous Immune Globulin (SCIg) Therapy
SCIg may be considered medically necessary for the treatment of primary immunodeficiencies (FDA-labeled indications) including congenital agammaglobulinemia, hypogammaglobulinemia, common variable immunodeficiency (CVID), severe combined immunodeficiency, Wiskott-Aldrich syndrome, and X-linked agammaglobulinemia (XLA).
Other applications of SCIg therapy are considered investigational, including, but not limited to chronic inflammatory demyelinating polyneuropathy (CIDP).
POLICY GUIDELINESPrimary Immunodeficiency Syndromes. The diagnosis of immunodeficiency and post immunization titers must be taken in context with the clinical presentation of the patient, and may vary dependent on the type of vaccine given and the prior immunization history of the patient. The following parameters are examples of criteria for diagnosis of the primary immunodeficiency syndromes.
According to a 2010 national guideline from Canada on immune globulin for primary immune deficiency, although higher trough levels of IVIg may be associated with clinical response; the goal of IVIg dose increases should be to improve clinical effectiveness and not merely to increase trough levels.
Acute, severe ITP may be defined by the following parameters:
Patients with chronic inflammatory demyelinating neuropathy (CIDP) should meet the diagnostic criteria established by the American Academy of Neurology. There is currently no criterion standard set of clinical or electrophysiologic criteria for the diagnosis of CIDP and its variants.
IVIg treatment in CIDP should be limited to patients who do not respond to initial therapy with prednisone and are experiencing serious clinical worsening. In patients treated for chronic diseases, such as CIDP, multifocal motor neuropathy, and dermatomyositis, the effect of IVIg is transitory and therefore periodic infusions of IVIg are needed to maintain treatment effect. The frequency of transfusions is titrated to the treatment response; typically, biweekly or monthly infusions are needed.
Medically Necessary is defined as those services, treatments, procedures, equipment, drugs, devices, items or supplies furnished by a covered Provider that are required to identify or treat a Member's illness, injury or Nervous/Mental Conditions, and which Company determines are covered under this Benefit Plan based on the criteria as follows in A through D:
A. consistent with the symptoms or diagnosis and treatment of the Member's condition, illness, or injury; and
B. appropriate with regard to standards of good medical practice; and
C. not solely for the convenience of the Member, his or her Provider; and
D. the most appropriate supply or level of care which can safely be provided to Member. When applied to the care of an Inpatient, it further means that services for the Member's medical symptoms or conditions require that the services cannot be safely provided to the Member as an Outpatient.
For the definition of Medically Necessary, “standards of good medical practice” means standards that are based on credible scientific evidence published in peer-reviewed medical literature generally recognized by the relevant medical community, and physician specialty society recommendations, and the views of medical practitioners practicing in relevant clinical areas and any other relevant factors. BCBSMS makes no payment for services, treatments, procedures, equipment, drugs, devices, items or supplies which are not documented to be Medically Necessary. The fact that a Physician or other Provider has prescribed, ordered, recommended, or approved a service or supply does not in itself, make it Medically Necessary.
Investigative is defined as the use of any treatment procedure, facility, equipment, drug, device, or supply not yet recognized as a generally accepted standard of good medical practice for the treatment of the condition being treated and; therefore, is not considered medically necessary. For the definition of Investigative, “generally accepted standards of medical practice” means standards that are based on credible scientific evidence published in peer-reviewed medical literature generally recognized by the relevant medical community, and physician specialty society recommendations, and the views of medical practitioners practicing in relevant clinical areas and any other relevant factors. In order for equipment, devices, drugs or supplies [i.e, technologies], to be considered not investigative, the technology must have final approval from the appropriate governmental bodies, and scientific evidence must permit conclusions concerning the effect of the technology on health outcomes, and the technology must improve the net health outcome, and the technology must be as beneficial as any established alternative and the improvement must be attainable outside the testing/investigational setting.
The coverage guidelines outlined in the Medical Policy Manual should not be used in lieu of the Member's specific benefit plan language.
POLICY HISTORY8/1997: Approved by Medical Policy Advisory Committee (MPAC)
8/1999: Revisions approved by MPAC
11/1999: Revisions approved by Pharmacy & Therapeutics (P & T) Committee
5/2001: Reviewed by MPAC; IgIV considered medically necessary for CIDP
1/30/2002: Venoglobulin I® deleted from ITP; Venoglobulin S®, Gammagond SD, Polygam SD added to Kawasaki syndrome
2/15/2002: Investigational definition added
5/1/2002: Type of Service and Place of Service deleted
5/29/2002: Code Reference section updated
11/6/2002: Prior authorization required
3/25/2003: Policy section revised, "CLL with frequent infections" deleted, CPT code range 90281-90399 deleted
7/2003: Reviewed by MPAC, Policy section aligned with BCBSA, treatment dosage information deleted, ICD-9 diagnosis code ranges 356.0-356.9, 493.00-493.91, 203.00-203.81, 714.0-714.9 listed separately, ICD-9 diagnosis code 695.4 deleted covered codes, ICD-9 diagnosis code 203.00-203.81, 288.0, 493.00-493.91 moved to non-covered codes, ICD-9 diagnosis code 493.92 added non-covered codes
10/13/2004: Code Reference section updated, CPT code 90780, 90781 deleted covered codes, ICD-9 diagnosis code 279.00, 279.04, 279.05, 279.12, 279.2, 357.82, 358.01, 776.1, V42.0, V42.1, V42.6, V42.7, V42.83 added covered codes, ICD-9 diagnosis code 357.0, 446.1 description revised, ICD-9 diagnosis 358.0 5th digit added, HCPCS J0850 added covered codes, HCPCS J1561 effective deletion date added, HCPCS J1562 deleted, non-covered ICD-9 diagnosis code 203.00-203.81, 288.0, 493.00-493.91, 493.92, 710.0, 714.0-714.9 deleted
11/11/05: Policy description revised: Intravenous immune globulin (IgIV) changed to (IVIg). Policy section language revised: Preferred provider changed to Accredo; telephone # changed from 1-866-591-9075 to 1-866-240-3373; fax # changed from 1-866-591-9094 to 1-800-711-3526. Policy section description revised for intravenous immune globulin therapy diagnoses related to medical necessity. Added paragraph for intravenous immune globulin therapy. Deleted under intravenous immune gloublin therapy: agammaglobulinemia - primary humoral, hypogammaglobulinemia - primary humoral immundeficiency, bacterial infections associated with B-Cell chronic lymphocytic leukemia (CLL), HIV-ITP with severe bleeding using pooled nonspecific IVIG preparations, prevention of infection in HIV-infected children(Gamimune N® only), solid organ transplant recipients at risk for cytomegalovirus infections and pneumonia (Cytogam® only). Vital capacity less than 1L, dysphagia associated with aspiration and inability to ambulate 100 feet without assistance deleted from definition of myasthenia gravis. Deleted hereditary and idiopathic peripheral neuropathy, bone marrow transplant patients; and relapsing/remitting multiple sclerosis. Policy section description revised for polymyositis under the intravenous immune globulin therapy section related to investigational diagnoses; added chronic progressive multiple sclerosis. Code Reference section updated: 5th digit added to ICD9 diagnosis code 287.31, description revised; HCPCS codes J1564, Q9941-Q9944 added, J1561 deleted.
11/2005: Approved by Pharmacy & Therapeutics (P & T) Committee
3/14/2006: Coding updated. HCPCS 2006 revisions added to policy
3/20/2006: Policy reviewed, no changes
7/27/2006: Policy revised. Revisions approved by Medical Policy Advisory Committee (MPAC)
6/14/2007: Code Reference section updated per quarterly HCPCS and Category III revisions
12/19/2007: Coding updated per 2008 CPT/HCPCS revisions
1/18/2008: Policy revised to add "Policy" section on SCIg and maternal-fetal tolerance
1/21/2008: Code reference section revised; CPT 90284 and HCPCS J1562 added to covered codes. Added non-covered codes table; CPT 86021, 86355, 86357, 86360, 86361, and 86849 added to non-covered codes for techniques to investigate immunologic abnormalities affecting maternal-fetal tolerance. Policy named changed from "Intravenous Immune Globulin (IVIg)" to "Immune Globulin Replacement Therapy".
9/22/2008: Annual ICD-9 updates effective 10-1-2008 applied
1/1/2009:Accredo preferred provider information removed. BCBSMS information added.
1/6/2009: Policy reviewed, the following specifically listed under investigational:
4/23/2009: ICD-9 code 340 deleted from covered table
10/11/2010: Updated the Code Reference section to remove 86360 and 86361 from the non-covered codes table.
02/28/1011: Added new HCPCS codes J1559 and J1599 to the Code Reference section.
01/17/2012: Policy statement reformatted for clarity purposes. Add the following as medically necessary indications: Acute Humoral Rejection, Autoimmune Mucocutaneous Blistering Diseases, warm antibody autoimmune hemolytic anemia, refractory to corticosteroids and immunosuppressive agents, anti-phospholipid syndrome, and toxic shock syndrome. Added the following indications to the investigational policy statement: complex regional pain syndrome, Alzheimer’s disease, IGG sub-class deficiency, and sepsis. Deleted the statement regarding laboratory tests to investigate immunologic abnormalities affecting maternal-fetal tolerance. Policy guidelines updated regarding laboratory testing. Deleted the Non-Covered codes table. Deleted outdated references from the Sources section.
04/09/2013: Policy reviewed. Added neonatal sepsis and Crohn's disease as investigational indications. Removed deleted codes J1567 and Q4087 - Q4092 from the Code Reference section.
11/15/2013: Policy statement updated to add severe anemia due to parvovirus B19 as medically necessary. Added opsoclonus-myoclonus, birdshot retinopathy, epidermolysis bullosa acquisita, necrotizing fasciitis, and polyradiculoneuropathy (other than CIDP) as investigational indications.
10/30/2014: Policy reviewed. Updated the criteria for patients with primary immunodeficiency syndromes to include laboratory evidence of immunoglobulin deficiency. Removed Kawasaki disease from the list of Infectious diseases. Added prevention of infection in preterm (<37 weeks’ gestational age) and/or low-birth weight (<2500g) neonates as medically necessary. Added hemophagocytic lymphohistiocytosis as another name for hemophagocytic syndrome. Added the following investigational statement: Other applications of SCIg therapy are considered investigational, including, but not limited to chronic inflammatory demyelinating polyneuropathy (CIDP).
08/27/2015: Code Reference section updated to add ICD-10 codes.
11/18/2015: Policy guidelines updated to add medically necessary and investigative definitions. Code Reference section updated to add HCPCS code J1556.
12/17/2015: Policy title changed from "Immune Globulin Replacement Therapy" to "Immune Globulin Therapy." Policy description re-written. Added the following policy statement: IVIg therapy may be considered medically necessary for the following indications. Medically necessary criteria updated to make the following changes: "Primary Immune Deficiency Syndromes" changed to "Primary Humoral Immune Deficiency Syndromes;" "Bruton's" changed to "Bruton agammaglobulinemia;" added "hemolytic disease of the fetus and newborn (aka erythroblastosis fetalis)" to the hematologic criteria; and "allogeneic post-bone marrow transplant setting" changed to "post-allogeneic bone marrow transplant setting." Investigational statement for IVIg updated to change "treatment of sepsis including neonatal sepsis" to "treatment of sepsis including suspected or proven infection in neonates." Postpolio syndrome added as investigational. Policy guidelines updated regarding diagnosis of patients with CIDP. Code Reference section updated to add ICD-10 diagnosis codes P55.8 and P55.9.
05/27/2016: Policy number added.
07/22/2016: Policy description updated regarding FDA-approved products. Policy statements unchanged.
SOURCE(S)Blue Cross Blue Shield Association Policy # 8.01.05
CODE REFERENCEThis may not be a comprehensive list of procedure codes applicable to this policy.
The code(s) listed below are ONLY medically necessary if the procedure is performed according to the "Policy" section of this document.