BlueCross BlueShield of Tennessee Medical Policy Manual

Intravenous Immune Globulin (IVIG) Therapy

DESCRIPTION

Intravenous immune globulin, (i.e., IGIV or IVIG) is used to provide passive immunity or to alter the immune response by increasing the individual's antibody titer and antigen-antibody reaction potential. Five major classes of immunoglobulin proteins exist in human serum and other body fluids. The five types are: IgA, IgD, IgE, IgG and IgM.

Gamma globulins are specialized proteins (antibodies) made by the body's immune system. Each antibody is shaped to interact with a specific target molecule found on the surface of bacteria, viruses or other infectious agents. Whenever antibodies react with their targets, the immune system may be activated to protect the body against that target. In diseases like hypogammaglobulinemia and chronic lymphocytic leukemia, the body does not make enough gamma globulin to protect against infection. In diseases like dermatomyositis the body produces abnormal gamma globulins that are shaped to interact with "targets" inside the body itself. Immune globulin is an antibody-containing solution obtained from the pooled plasma of healthy blood donors.

Examples of preparations of intravenous immune globulins are: Carimune NF, Gamimune, Gammagard S/D, Gamunex, Flebogamma, Gammar-P, Iveegam, Panglobulin, Polygam S/D, Sandoglobulin, Privigen and Venoglobulin.

REFER TO DECISION SUPPORT TREE

POLICY

Human intravenous immune globulin therapy for the treatment of primary immunodeficiencies (e.g. congenital agammaglobulinemia [X-linked agammaglobulinemia], hypogammaglobulinemia, common variable immunodeficiency, X-linked immunodeficiency with hyperimmunoglobulin M, severe combined immunodeficiency [SCID], Wiskott-Aldrich syndrome) is considered medically necessary.

Human intravenous immune globulin therapy as a treatment adjunct when administered with aspirin for Kawasaki disease is considered medically necessary.

Human intravenous immune globulin therapy as a treatment adjunct for the prevention of recurrent bacterial infections associated with B-cell chronic lymphocytic leukemia (CLL) is considered medically necessary.

Human intravenous immune globulin therapy as a treatment adjunct to prevent the risk of acute graft-versus-host disease is considered medically necessary if the medical appropriateness criteria are met. (See Medical Appropriateness below.)

Human intravenous immune globulin therapy for the treatment of idiopathic thrombocytopenic purpura (ITP) when a rise in platelet count is required (e.g., prior to surgery, to control excessive bleeding, to defer or avoid a splenectomy, or to prevent bleeding post-splenectomy) is considered medically necessary.

Human intravenous immune globulin therapy for the prevention of serious bacterial infections associated with pediatric human immunodeficiency virus (HIV) or Aids-related complex (ARC) is considered medically necessary..

Human intravenous immune globulin therapy for the treatment of acute Guillain-Barré syndrome is considered medically necessary if the medical appropriateness criteria are met. (See Medical Appropriateness below.)

Human intravenous immune globulin therapy for the treatment of dermatomyositis as second-line treatment agent is considered medically necessary if the medical appropriateness criteria are met. (See Medical Appropriateness below.)

Human intravenous immune globulin therapy for the treatment of relapsing-remitting multiple sclerosis as a second-line treatment agent is considered medically necessary.

Human intravenous immune globulin therapy for prophylaxis and treatment adjunct of infections in neonates is considered medically necessary.

Human intravenous immune globulin therapy for the treatment of chronic parvovirus B19 infection and severe anemia secondary to bone marrow suppression is considered medically necessary.

Human intravenous immune globulin therapy for the treatment of chronic inflammatory demyelinating polyneuropathies is considered medically necessary.

Human intravenous immune globulin therapy for the treatment of multifocal motor neuropathy (MMN) as a second-line agent is considered medically necessary.

Human intravenous immune globulin therapy for the treatment of Lambert-Eaton myasthenic syndrome is considered medically necessary.

Human intravenous immune globulin therapy for the treatment of hyperimmunoglobulinemia E syndrome is considered medically necessary.

Human intravenous immune globulin therapy for the treatment of a solid organ transplant is considered medically necessary if the medical appropriateness criteria are met. (See Medical Appropriateness below.)

Human intravenous immune globulin therapy for the treatment of other conditions/diseases including, but not limited to, the following is considered investigational: (See Applicable Tennessee State Mandate Requirements below.)

Alopecia universalis	Myasthenia gravis
Anemia	Myocarditis
Antenatal and neonatal thrombocytopenia	Myositis
Antiphospholipid antibody syndrome (APS)	Neonatal jaundice
Aplasia, pure red cell	Neuropathy
Asthma	Nodular pemphigoid
Autoimmune neutropenia	Ocular cicatricial pemphigoid
Behçet's syndrome	Otitis media
Bullous pemphigoid	Paraneoplastic pemphigus
Burns	Paraneoplastic visual loss
Cardiac transplant	Pemphigus foliaceus
Chronic fatigue syndrome	Pemphigus gestationis
Clostridium induced colitis	Pemphigus vulgaris
Crohn's disease	Polymyositis
Cutaneous polyarteritis nodosa	Post transplant lymphoproliferative disorder
Cystic fibrosis	Posttransfusion purpura
Diabetic amyotrophy	Pyoderma gangrenous
Encephalomyelitis - acute, disseminated	Recurrent fetal loss
Epidermolysis bullosa acquisita	Renal transplant
Epilepsy	Respiratory syncytial virus
Epstein-Barr induced cerebellar ataxia	Rheumatoid arthritis
Hematopoietic stem cell recipients	Stevens-Johnson syndrome
Hemolytic uremic syndrome	Stiff man syndrome
Hemophagocytic syndrome	Still's disease
Hemophilia	Systemic lupus erythematosus (SLE)
Hopkins' syndrome	Systemic vasculitis
In Vitro fertilization	Nonimmune thrombocytopenia
Infection prophylaxis	Quinine-induced thrombocytopenia
Isaac's syndrome	Refractory to platelet transfusion
Juvenile rheumatoid arthritis	Septic thrombocytopenia
Leukocytoclastic vasculitis	Thrombotic thrombocytopenic purpura
Linear immunoglobulin - A disease	Toxic shock syndrome
Lysinuric protein intolerance	Uveitis
Malaria	Von Willebrand's syndrome
Multiple Myeloma	Wegener's granulomatosis

MEDICAL APPROPRIATENESS

Human intravenous immune globulin therapy as a treatment adjunct to prevent the risk of acute graft-versus-host disease (i.e., GVHF) is considered medically appropriate for individuals who meet all of the following criteria:

They are of 20 years of age or older
The agent is administered in the first 100 days after bone marrow transplantation
GVHF is associated with interstitial pneumonia (e.g., infectious or idiopathic) or infections (e.g., varicella-zoster virus infection, recurrent bacterial infection)

Human intravenous immune globulin therapy for the treatment of acute Guillain-Barré syndrome is considered medically appropriate for individuals who meet all of the following criteria:

They are 18 years of age or older
So severely impaired by Guillain-Barré they require assistance to walk
The disorder was diagnosed within the first two weeks of the illness

Human intravenous immune globulin therapy for the treatment of dermatomyositis as second-line treatment agent is considered medically appropriate for individuals who meet any of the following criteria:

They are corticosteroid-resistant
Corticosteroids are contraindicated

Human intravenous immune globulin therapy for the treatment of a solid organ transplant is considered medically appropriate if any of the medical appropriateness criteria are met.

Prior to a solid-organ transplant for individuals at high risk for antibody-mediated rejection, including highly sensitized individuals, and those receiving an ABO (blood type) incompatible organ
Following a solid-organ transplant for the treatment of an antibody-mediated rejection

APPLICABLE TENNESSEE STATE MANDATE REQUIREMENTS

Tennessee State law requires coverage of off-label indications of Food and Drug Administration (FDA) approved drugs when the off-label use is relative to life-threatening illnesses, such as cancer, AIDS, and coronary heart disease and recognized in one of the standard reference compendia (As defined in the statute: The United States Pharmacopoeia Drug Information, The American Medical Association Drug Evaluations, & The American Hospital Formulary Service Drug Information) or in the medical literature. This law is applicable to all fully insured members. The law is not applicable to self-funded accounts.

In addition to the FDA approved indications, a single pharmacy compendium, Drugdex, and the BlueCross BlueShield Association Medical Policy Manual, also recognize the use of IVIG in the treatment of:
Myasthenic crisis (i.e., an acute episode of respiratory muscle weakness) in patients with contraindications to plasma exchange; and
Myasthenia gravis in patients with chronic debilitating disease in spite of treatment with cholinesterase inhibitors, or complications from or failure of steroids and/or azathioprine.

ADDITIONAL INFORMATION

For appropriate dosage information, contraindications, precautions, warnings, and monitoring information, please refer to one of the standard reference compendia (e.g., The American Hospital Formulary Service Drug Information).

Severe thrombocytopenia is defined as a platelet count less than 20,000 / µL.

No controlled studies were found in published literature that validate the use of intravenous immune globulin (IVIG) for the prevention or treatment of other conditions/diseases.

SOURCES

BlueCross BlueShield Association. Medical Policy Reference Manual. (2:2006). Intravenous immune globulin therapy (8.01.05). Retrieved December 18, 2007 from BlueWeb.

CIGNA Government Services. Medicare Part B Carrier - Tennessee Local Coverage Determination. (2008, January). LCD for intravenous immunoglobulin (IVIG) (L6593). Retrieved December 29, 2007 from http://www.cms.hhs.gov/mcd/viewlcd.asp?lcd_id=6593&lcd_version=34&show=all

Complete Guide to Medicare Coverage Issues [Computer software]. (2007, November). Coverage of intravenous immune globulin for treatment of primary immune deficiency disease in the home (50.6, p. 4-194). St. Anthony Publishing.

Complete Guide to Medicare Coverage Issues [Computer software]. (2007, November). Intravenous immune globulin for treatment of autoimmune mucocutaneous blistering diseases (NDC 250.3, p. 2-195). St. Anthony Publishing.

Intravenous immunoglobulin (IVIG). (2006, December). The Medical Letter On Drugs and Therapeutics, 48 (Issue 1249/1250), 101-103.

Lexi-Comp Online. (2008). AHFS DI. Immune globulin®. Retrieved January 11, 2008 from Lexi-Comp Online with AHFS.

MICROMEDEX Healthcare Series. Drugdex Drug Evaluation. (2008). Immune globulin intravenous (human) (system). January 11, 2008 from MICROMEDEX Healthcare Series.

U. S. Food and Drug Administration. Center for Biologics Evaluation and Research. (2007, July). Product Approval Information. Immune globulin intravenous (human) 10% liquid (Privigen). Retrieved January 16, 2008 from http://www.fda.gov/cber/products/privigen.htm.

U. S. Food and Drug Administration. Center for Biologics Evaluation and Research. (2003, August). Product Approval Information. Immune globulin intravenous [human], 10% caprylate/chromatography purified (Gamunex®). Retrieved January 16, 2008 from http://www.fda.gov/cber/label/igivbay082703LB.pdf.

U. S. Food and Drug Administration. Center for Biologics Evaluation and Research. (2007, August). Immune globulin intravenous (IGIV) indications. Retrieved January 16, 2008 from http://www.fda.gov/cber/products/igivlist.htm.

ORIGINAL EFFECTIVE DATE: 12/4/1997

MOST RECENT REVIEW DATE: 6/14/2008

ID_BT

Policies included in the Medical Policy Manual are not intended to certify coverage availability. They are medical determinations about a particular technology, service, drug, etc. While a policy or technology may be medically necessary, it could be excluded in a member's benefit plan. Please check with the appropriate claims department to determine if the service in question is a covered service under a particular benefit plan. Use of the Medical Policy Manual is not intended to replace independent medical judgment for treatment of individuals. The content on this Web site is not intended to be a substitute for professional medical advice in any way. Always seek the advice of your physician or other qualified health care provider if you have questions regarding a medical condition or treatment.

Pharmaceutical Decision Support Tree

Intravenous Immune Globulin (IVIG) Therapy (Carimune NF, Gamimune, Gammagard S/D, Gamunex, Flebogamma, Gammar-P, Iveegam, Panglobulin, Polygam S/D, Privigen, Sandoglobulin and Venoglobulin)

Is the requested medication being used to treat alopecia universalis, anemia, antenatal and neonatal thrombocytopenia, antiphospholipid antibody syndrome (APS), aplasia, pure red cell, asthma, Behçet's syndrome, bullous pemphigoid, burns, cardiac transplant, chronic fatigue syndrome, clostridium induced colitis, Crohn's disease, cutaneous polyarteritis nodosa, cystic fibrosis, diabetic amyotrophy, encephalomyelitis - acute, disseminated, epidermolysis bullosa acquisita, epilepsy, Epstein-Barr induced cerebellar ataxia, hemolytic uremic syndrome, hemophagocytic syndrome, hemophilia, hematopoietic stem cell recipients, Hopkins' syndrome, infection prophylaxis, in vitro fertilization, Isaac's syndrome, juvenile rheumatoid arthritis, linear immunoglobulin - A disease, post transplant lymphoproliferative disorder, leukocytoclastic vasculitis, lysinuric protein intolerance, malaria, multiple myeloma, myasthenia gravis, myocarditis, myositis, neonatal jaundice, neuropathy, autoimmune neutropenia, nodular pemphigoid, ocular cicatricial pemphigoid, otitis media, paraneoplastic visual loss, paraneoplastic pemphigus, pemphigus foliaceus, pemphigus gestationis, pemphigus vulgaris, polymyositis, posttransfusion purpura, pyoderma gangrenous, renal transplant, respiratory syncytial virus, rheumatoid arthritis, recurrent fetal loss, Stevens-Johnson syndrome, Stiff man syndrome, Still's disease, systemic lupus erythematosus (SLE), systemic vasculitis, thrombocytopenia refractory to platelet transfusion, thrombotic thrombocytopenic purpura, nonimmune thrombocytopenia, septic thrombocytopenia, quinine-induced thrombocytopenia, toxic shock syndrome, uveitis, Von Willebrand's syndrome or Wegener's granulomatosis?

If yes, this does not meet medical necessity and/or medical appropriateness criteria

If no, go to question #2

Is IVIG being used for the treatment of primary immunodeficiencies (e.g. congenital agammaglobulinemia [X-linked agammaglobulinemia], hypogammaglobulinemia, common variable immunodeficiency, X-linked immunodeficiency with hyperimmunoglobulin M, severe combined immunodeficiency [SCID], Wiskott-Aldrich syndrome)?