Intravenous Immune Globulin (IVIG) Therapy
DESCRIPTION
Immune globulins or immunoglobulins (Ig) are specialized glycoproteins which function as antibodies. Produced by plasma cells, there are five human isotypes of immunoglobulins, IgA, IgD, IgE, IgG and IgM. Of these, IgG, IgA and IgM are referred to as natural antibodies as they are produced without deliberate immunization or antigen exposure. IgD and IgE are generally produced in response to the introduction of foreign antigens to which they bind and deactivate. Together, all immunoglobulin isotypes are vital components of the body’s immune response.
IgG is the most common of the immunoglobulins, with multiple functions including placental antibody transfer, phagocytic cell surface binding and activating complement. Commercial preparations of intravenous immune globulins (IVIGs) are sterile, highly purified IgG products manufactured from large pools of human plasma, typically from 1000 or more healthy blood donors. They contain more than 95% unmodified IgG but only trace amounts of IgA and/or IgM. IVIGs are used in the treatment of multiple conditions.
Examples of preparations of intravenous immune globulins are: Carimune® NF, Gammagard® S/D, Gammagard® Liquid, Gamunex®, Flebogamma®, Privigen® and Octagam®.
REFER TO DECISION SUPPORT TREE
POLICY
Intravenous immune globulin (IVIG) for the treatment of the following is considered medically necessary:
Chronic inflammatory demyelinating polyneuropathies (CIDP)
Hyperimmunoglobulinemia E syndrome
Lambert-Eaton myasthenic syndrome
Primary humoral immunodeficiency, including, but not limited to, the following:
Congenital agammaglobulinemia (X-linked agammaglobulinemia)
Hypogammaglobulinemia
Common variable immunodeficiency
X-linked immunodeficiency with hyperimmunoglobulin M
Severe combined immunodeficiency (SCID)
Wiskott-Aldrich syndrome
Intravenous immune globulin (IVIG) for the treatment of the following is considered medically necessary if the medical appropriateness criteria are met: (See Medical Appropriateness below.)
Bacterial infections associated with neonates
Dermatomyositis
Guillain-Barré syndrome
Immune/idiopathic thrombocytic purpura (ITP)
Kawasaki disease
Multifocal motor neuropathy (MMN)
Multiple sclerosis
Solid organ transplant recipients
Parvovirus B19
Intravenous immune globulin (IVIG) for the prevention of serious bacterial infections in the following is considered medically necessary:
Individuals with pediatric human immunodeficiency virus (HIV)
Individuals with pediatric AIDS-related complex (ARC)
Intravenous immune globulin (IVIG) for the prevention of the following is considered medically necessary if the medical appropriateness criteria are met: (See Medical Appropriateness below.)
Bacterial infections associated with the following:
Chronic lymphocytic leukemia (CLL)
Neonates
Graft-versus-host disease
Intravenous immune globulin (IVIG) for the treatment of other conditions/diseases, including, but not limited to the following is considered investigational: (See Applicable Tennessee State Mandate Requirements below.)
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Intravenous immune globulin (IVIG) for the treatment of ANY ONE of the following is considered medically appropriate if the criteria are met:
Bacterial infections associated with neonates if treatment is adjunctive (i.e., to increase efficacy of primary treatment regimen)
Dermatomyositis if ALL of the following criteria are met:
Agent is used as second-line therapy (i.e., after failure of initial treatment of choice)
Corticosteroid therapy is ANY ONE of the following:
Contraindicated
Ineffective due to proven resistance
Guillain-Barré syndrome (GBS) if ALL the following criteria are met:
Individual is 18 years of age or older
Disease is acute
GBS diagnosis is made within the first two weeks of the illness
Individual requires assistance to walk due to severity of GBS impairment
Immune/idiopathic thrombocytic purpura (ITP) if 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)
Kawasaki disease if administered with aspirin
Multifocal motor neuropathy (MMN) as second-line therapy (i.e., after failure of initial treatment of choice)
Multiple sclerosis if ALL of the following criteria are met:
Disease is relapsing-remitting
Treatment is second-line treatment therapy (i.e., after failure of initial treatment of choice)
Solid organ transplant recipients if ANY ONE of the following criteria are met:
Pre-transplant, individual is at high risk for antibody-mediated rejection, (e.g., highly sensitized individuals or those receiving an ABO/blood type incompatible organ)
Post-transplant, for treatment of an antibody-mediated rejection
Parvovirus B19 if ALL the following criteria are met:
Disease is chronic
Individual has severe anemia secondary to bone marrow suppression
Intravenous immune globulin (IVIG) for the prevention of ANY ONE of the following is considered medically appropriate if the criteria are met:
Bacterial infections associated with ANY ONE of the following:
Chronic lymphocytic leukemia (CLL) if ALL of the following criteria are met:
Infections are recurrent
Treatment is adjunctive (i.e., to increase efficacy of primary treatment regimen)
Neonates if the if treatment is adjunctive (i.e., to increase efficacy of primary treatment regimen)
Graft-versus-host disease (GVHF) if ALL of the following criteria are met:
Treatment is adjunctive (i.e., to increase efficacy of primary treatment regimen)
Individual is 20 years of age or older
GVHF is acute
IVIG is administered in the first 100 days after bone marrow transplantation
GVHF is associated with ANY ONE of the following:
Interstitial pneumonia (e.g., infectious or idiopathic)
Infections (e.g., varicella-zoster virus infection, recurrent bacterial infection)
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. This law is applicable to all fully insured members. The law is not applicable to self-funded accounts, but coverage for off-label uses may be provided based on the contractual agreement.
The BlueCross BlueShield Association Medical Policy Manual 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
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
The American Hospital Formulary Service Drug Information (AHFS-DI) recognizes the use of IVIG in the treatment of varicella prophylaxis in the event that varicella zoster immune globulin (VZIG) is unavailable.
A multicenter, randomized, placebo-controlled, double-blind clinical trial recognizes the use of IVIG in the treatment of biopsy-proven autoimmune mucocutaneous blistering diseases (e.g., pemphigus vulgaris, pemphigus foliaceus).
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).
No controlled studies were found in the published literature that validate the use of intravenous immune globulins in the treatment or prevention of other conditions/diseases.
SOURCES
Amagai, M., Ikeda, S., Shimizu, H., Iizuka, H., Hanada, K., Aiba, S., et al. (2009). A randomized double-blind trial of intravenous immunoglobulin for pemphigus. Journal of the American Academy of Dermatology, 60 (4), 595-603. (Level 1 Evidence)
Baxter Pharmaceuticals (2008, October). Gammagard® S/D immune globulin intravenous (human). Retrieved July 24, 2009 from http://www.baxter.com/products/biopharmaceuticals/downloads/gammagard_us_pi.pdf?WT.svl=BiosciencePIs&site=www.immunedisease.com.
BlueCross BlueShield Association. Medical Policy Reference Manual. (12:2008). Immune Globulin Therapy (8.01.05). Retrieved June 24, 2009 from BlueWeb.
Complete Guide to Medicare Coverage Issues [Computer software]. (2009, April). Intravenous immune globulin for the treatment of autoimmune mucocutaneous blistering diseases (NCD 250.3, p. 2-200). The Ingenix Complete Guide to Medicare Coverage Issues.
Grifols, Inc. (2005, January). Flebogamma® 5%: Immune globulin intravenous (Human). Retrieved July 6, 2009 from http://www.grifolsusa.com/pdfs/flebo_14Jun05.pdf.
Immune Deficiency Foundation. (2008, August). Characteristics of Available Immune Globulin Products Licensed for Use in the United States. Retrieved July 6, 2009 from http://www.primaryimmune.org/patients_families/prod_safe/ivig_chart.pdf.
Lexi-Comp Online. (2009). AHFS DI. Immune globulin. Retrieved April 29, 2009 from Lexi-Comp Online with AHFS.
MICROMEDEX Healthcare Series. Drugdex Drug Evaluations. (2009). Immune globulin. Retrieved June 23, 2009 from MICROMEDEX Healthcare Series.
National Comprehensive Cancer Network. (2009). NCCN Drugs & Biologics Compendium™. Immune globulin intravenous (human). Retrieved April 29, 2009 from http://www.nccn.org/professionals/drug_compendium/mainpage.aspx.
U. S. Department of Health & Human Services. Centers for Medicare & Medicaid Services. LMRPs/LCDs for CIGNA Government Services. (2009, March). LCD for Intravenous Immune Globulin (L27259). Retrieved June 24, 2009 from http://www.cms.hhs.gov/mcd/viewlcd.asp?lcd_id=27259&lcd_version=9&show=all.
U. S. Food and Drug Administration. (2006, February). Center for Biologics Evaluation and Research. Octagam®: Immune globulin intravenous, Human 5%. Retrieved July 6, 2009 from http://www.fda.gov/downloads/BiologicsBloodVaccines/BloodBloodProducts/ApprovedProducts/LicensedProductsBLAs/FractionatedPlasmaProducts/ucm064946.pdf.
U. S. Food and Drug Administration. (2009, May). Center for Biologics Evaluation and Research. Carimune® NF, Nanofiltered: Immune Globulin Intravenous (Human). Retrieved June 24, 2009 from http://www.fda.gov/downloads/BiologicsBloodVaccines/UCM152763.pdf.
U. S. Food and Drug Administration. (2009, May). Center for Biologics Evaluation and Research. Gamunex® (Immune globulin intravenous [Human], 10% caprylate/chromatography purified). Retrieved April 29, 2009 from http://www.fda.gov/downloads/BiologicsBloodVaccines/BloodBloodProducts/ApprovedProducts/LicensedProductsBLAs/FractionatedPlasmaProducts/ucm069968.pdf.
U. S. Food and Drug Administration. (2009, May). Center for Biologics Evaluation and Research. Immune globulin intravenous (Human), 10% Liquid: Privigen®. Retrieved July 6, 2009 from http://www.fda.gov/downloads/BiologicsBloodVaccines/BloodBloodProducts/ApprovedProducts/LicensedProductsBLAs/FractionatedPlasmaProducts/ucm069975.pdf.
U. S. Food and Drug Administration. (2009, May). Center for Biologics Evaluation and Research. Vaccines, blood & biologics Immune globulin intravenous (IGIV) indications. Retrieved July 6, 2009 from http://www.fda.gov/BiologicsBloodVaccines/BloodBloodProducts/ApprovedProducts/LicensedProductsBLAs/FractionatedPlasmaProducts/ucm133691.htm.
ORIGINAL EFFECTIVE DATE: 12/4/1997
MOST RECENT REVIEW DATE: 12/12/2009
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, Gammagard® S/D, Gammagard® Liquid, Gamunex®, Flebogamma®, Privigen® and Octagam®)
Is the requested medication being used to treat ANY ONE of the following conditions?
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
If yes, this does not meet medical necessity and/or medical appropriateness criteria
If no, go to question #2
Does the individual have a diagnosis of ANY ONE of the following?
Chronic inflammatory demyelinating polyneuropathies (CIDP)
Hyperimmunoglobulinemia E syndrome
Lambert-Eaton myasthenic syndrome
Pediatric AIDS-related complex (ARC) (i.e., for serious bacterial infection prevention)
Pediatric human immunodeficiency virus (HIV) (i.e., for serious bacterial infection prevention)
Primary humoral immunodeficiency, including, but not limited to, ANY ONE of the following:
Congenital agammaglobulinemia (X-linked agammaglobulinemia)
Hypogammaglobulinemia
Common variable immunodeficiency
X-linked immunodeficiency with hyperimmunoglobulin M
Severe combined immunodeficiency (SCID)
Wiskott-Aldrich syndrome
If yes, this satisfies medical necessity and medical appropriateness criteria
If no, go to question #3
Is the individual a neonate with bacterial infections or at risk for infections?
If yes, go to question #4
If no, go to question #5
Is the treatment is adjunctive to treat or prevent bacterial infections?
If yes, this satisfies medical necessity and medical appropriateness criteria
If no, this does not meet medical necessity and/or medical appropriateness criteria
Does the individual have a diagnosis of dermatomyositis?
If yes, go to question #6
If no, go to question #8
Is treatment with IVIG second-line therapy (i.e., after failure of initial treatment of choice)?
If yes, go to question #7
If no, this does not meet medical necessity and/or medical appropriateness criteria
Is corticosteroid therapy contraindicated or ineffective due to proven resistance?
If yes, this satisfies medical necessity and medical appropriateness criteria
If no, this does not meet medical necessity and/or medical appropriateness criteria
Does the individual have a diagnosis of Guillain-Barré syndrome (GBS) with ALL of the following?
Individual is 18 years of age or older
Disease is acute
GBS diagnosis is made within the first two weeks of the illness
Individual requires assistance to walk due to severity of GBS impairment
If yes, this satisfies medical necessity and medical appropriateness criteria
If no, go to question #9
Does the individual have a diagnosis of immune/idiopathic thrombocytic purpura (ITP) and 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)?
If yes, this satisfies medical necessity and medical appropriateness criteria
If no, go to question #10
Does the individual have a diagnosis of Kawasaki disease and will take aspirin with therapy if tolerated?
If yes, this satisfies medical necessity and medical appropriateness criteria
If no, go to question #11
Does the individual have a diagnosis of multifocal motor neuropathy and treatment is second line?
If yes, this satisfies medical necessity and medical appropriateness criteria
If no, go to question #12
Does the individual have a diagnosis of multiple sclerosis with ALL of the following?
Disease is relapsing-remitting
Treatment is second-line treatment therapy
If yes, this satisfies medical necessity and medical appropriateness criteria
If no, go to question #13
Is the individual a solid organ transplant recipient with ANY ONE of the following?
Pre-transplant, individual is at high risk for antibody-mediated rejection, (e.g., highly sensitized individuals or those receiving an ABO/blood type incompatible organ)
Post-transplant, for treatment of an antibody-mediated rejection
If yes, this satisfies medical necessity and medical appropriateness criteria
If no, go to question #14
Does the individual have a diagnosis of chronic parvovirus B19 with severe anemia secondary to bone marrow suppression?
If yes, this satisfies medical necessity and medical appropriateness criteria
If no, go to question #15
Is the individual at risk for bacterial infections associated with chronic lymphocytic leukemia with ALL of the following?
Recurrent infections
Treatment is adjunctive
If yes, this satisfies medical necessity and medical appropriateness criteria
If no, go to question #16
Is the individual at risk for graft-versus-host disease (GVHF) associated with interstitial pneumonia (infectious or idiopathic) or infections such as varicella-zoster infection or recurrent bacterial infections with ALL of the following:
Treatment is adjunctive
Individual is 20 years of age or older
GVHF is acute
IVIG is administered in the first 100 days after bone marrow transplantation
If yes, this satisfies medical necessity and medical appropriateness criteria
If no, this does not meet medical necessity and/or medical appropriateness criteria
This document has been classified as public information.