BlueCross BlueShield of Tennessee Medical Policy Manual

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.  IVIG products 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® and Privigen®.

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)

• Lambert-Eaton myasthenic syndrome

• Primary immunodeficiencies /defective antibody synthesis (i.e., genetic defects), limited to the following:

• Common variable immunodeficiency

• Hyperimmunoglobulin E (Hyper-IgE) syndrome

• Severe combined immunodeficiency (SCID)

• Wiskott-Aldrich syndrome (thrombocytopenia and eczema)

• X-linked agammaglobulinemia

• X-linked hyperimmunoglobulin M (Hyper-IgM) 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

• Myasthenia gravis

• Parvovirus B19

• Transplant recipients (e.g., solid organ, stem cell/bone marrow)

• 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

• Pediatric human immunodeficiency virus (HIV)

• Pediatric AIDS-related complex (ARC)

• 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.)

See also:

• Palivizumab

• Rh0(D) Immune Globulin

MEDICAL APPROPRIATENESS

• 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 is diagnosed within the first two weeks of disease onset

• 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 / avoid 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)

• Myasthenia gravis if ANY ONE of the following:

• Disease is considered chronic debilitating in spite of treatment with ANY ONE of the following:

• Cholinesterase inhibitors

• Steroids

• Azathioprine

• Individual is in myasthenic crisis and plasma exchange is contraindicated

• Parvovirus B19 if ALL the following criteria are met:

• Disease is chronic

• Individual has severe anemia secondary to bone marrow suppression

• Transplant recipients if ANY ONE of the following are received:

• Hematopoietic cell transplant (regardless of cell source) with severe hypogammaglobulinemia (i.e., IgG levels less than 400 mg/dL)

• Solid organ transplant 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

• 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)

• Hematopoietic cell transplant (regardless of cell source) if hypogammaglobulinemia is severe (i.e., IgG levels less than 400 mg/dL)

• Graft-versus-host disease (GVHD) if ALL of the following criteria are met:

• Treatment is adjunctive (i.e., to increase efficacy of primary treatment regimen)

• GVHD is associated with ANY ONE of the following:

• Interstitial pneumonia (e.g., infectious or idiopathic)

• Infections (e.g., varicella-zoster virus, 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 American Hospital Formulary Service Drug Information (AHFS-DI) recognizes the use of IVIG in the following:

• Varicella postexposure prophylaxis in the event that varicella zoster immune globulin (VZIG) is unavailable.

• Treatment and postexposure prophylaxis of tetanus in the event that tetanus immune globulin (TIG) is not available

• Toxic shock syndrome

• 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).

IMPORTANT REMINDER

We develop Medical Policies to provide guidance to Members and Providers.  This Medical Policy relates only to the services or supplies described in it.  The existence of a Medical Policy is not an authorization, certification, explanation of benefits or a contract for the service (or supply) that is referenced in the Medical Policy.  For a determination of the benefits that a Member is entitled to receive under his or her health plan, the Member's health plan must be reviewed.  If there is a conflict between the Medical Policy and a health plan, the express terms of the health plan will govern.

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 (2009, December). Gammagard® S/D immune globulin intravenous (human). Retrieved March 24, 2011 from http://www.baxter.com/products/biopharmaceuticals/downloads/gammagard_us_pi.pdf?WT.svl=BiosciencePIs&site=www.gammagardliquid.com.

Baxter Pharmaceuticals (2010, December). Gammagard® Liquid immune globulin intravenous (human). Retrieved March 24, 2011 from http://www.baxter.com/products/biopharmaceuticals/downloads/gamliquid_PI.pdf?WT.svl=BiosciencePIs&site=www.gammagardliquid.com.

BlueCross BlueShield Association. Medical Policy Reference Manual. (12:2008). Immune Globulin Therapy (8.01.05). Retrieved June 24, 2009 from BlueWeb.

CSL Behring LLC. (2011, February). Privigen®, immune globulin intravenous. Retrieved March 24, 2011 from http://www.privigen.com/pdf/Privigen_PI.pdf.

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. (2011, March). AHFS DI. Immune globulin. Retrieved March 24, 2011 from Lexi-Comp Online with AHFS.

MICROMEDEX Healthcare Series. Drugdex Drug Evaluations. (2011, March). Immune globulin. Retrieved March 24, 2011 from MICROMEDEX Healthcare Series.

Talecris Biotherapeutics, Inc. (2010, October). Gamunex®-C [Immune globulin injection (Human) 10% caprylate/chromatography purified]. Retrieved March 24, 2011 from http://www.gamunex-c.com/media/Gamunex_Prescribing_Info.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. 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:  9/11/2011

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® and Privigen®)

1. 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

2. Does the individual have a diagnosis of ANY ONE of the following?

• Chronic inflammatory demyelinating polyneuropathies (CIDP)

• Lambert-Eaton myasthenic syndrome

• Primary immunodeficiencies /defective antibody synthesis (i.e., genetic defects), limited to the following:

• Common variable immunodeficiency

• Hyperimmunoglobulin E (Hyper-IgE) syndrome

• Severe combined immunodeficiency (SCID)

• Wiskott-Aldrich syndrome (thrombocytopenia and eczema)

• X-linked agammaglobulinemia

• X-linked hyperimmunoglobulin M (Hyper-IgM) syndrome

If yes, this satisfies medical necessity and medical appropriateness criteria

If no, go to question #3

3. Is the individual a neonate with bacterial infections requiring adjunctive treatment (i.e., requires increased efficacy of primary treatment regimen)?

If yes, this satisfies medical necessity and medical appropriateness criteria

If no, go to question #4

4. Does the individual have a diagnosis of dermatomyositis and has failed primary therapy and corticosteroids are either contraindicated or ineffective due to proven resistance?

If yes, this satisfies medical necessity and medical appropriateness criteria

If no, go to question #5

5. Is the individual 18 years of age or older with a diagnosis of acute Guillain-Barré syndrome (GBS) that was diagnosed within two weeks of onset and who requires assistance walking due to the severity of GBS impairment?

If yes, this satisfies medical necessity and medical appropriateness criteria

If no, go to question #6

6. Does the individual have a diagnosis of Immune/idiopathic thrombocytic purpura (ITP) and requires a rise in platelet count, such as prior to surgery, to control excessive bleeding, to defer / avoid splenectomy or to prevent bleeding post-splenectomy?

If yes, this satisfies medical necessity and medical appropriateness criteria

If no, go to question #7

7. Does the individual have a diagnosis of Kawasaki disease and the agent will be administered with aspirin?

If yes, this satisfies medical necessity and medical appropriateness criteria

If no, go to question #8

8. Does the individual have a diagnosis of multifocal motor neuropathy and the agent will be administered secondary to the failure of the initial treatment (i.e., second-line)?

If yes, this satisfies medical necessity and medical appropriateness criteria

If no, go to question #9

9. Does the individual have relapsing-remitting multiple sclerosis and treatment is second-line (i.e., after failure of initial treatment)?

If yes, this satisfies medical necessity and medical appropriateness criteria

If no, go to question #10

10. Does the individual have a diagnosis of chronic debilitating myasthenia gravis in spite of treatment with cholinesterase inhibitors, steroids or azathioprine?

If yes, this satisfies medical necessity and medical appropriateness criteria

If no, go to question #11

11. Is the individual with a diagnosis of myasthenia gravis in myasthenic crisis and a contraindication to plasma exchange?

If yes, this satisfies medical necessity and medical appropriateness criteria

If no, go to question #12

12. 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 #13

13. Is the individual a hematopoietic cell transplant recipient (regardless of cell source) with severe hypogammaglobulinemia defined as IgG levels less than 400 mg/dL?

If yes, this satisfies medical necessity and medical appropriateness criteria

If no, go to question #14

14. Is the individual a solid organ transplant recipient who, pre-transplant, is at high risk for antibody-mediated rejection (e.g., highly sensitized individuals or those receiving an ABO/blood type incompatible organ)?

If yes, this satisfies medical necessity and medical appropriateness criteria

If no, go to question #15

15. Is the individual a solid organ transplant recipient who, post-transplant, requires treatment of an antibody-mediated rejection?

If yes, this satisfies medical necessity and medical appropriateness criteria

If no, go to question #16

16. Is the agent to be used for the prevention of infections associated with ANY ONE of the following?

• Chronic lymphocytic leukemia (CLL) with recurrent bacterial infections and treatment is adjunctive

• Neonates with bacterial infections if treatment is adjunctive

• Hematopoietic cell transplant (regardless of cell source) if hypogammaglobulinemia is severe (i.e., IgG levels less than 400mg/dL)

• Graft-versus-host disease (GVHD) if associated with infectious / idiopathic interstitial pneumonia or infections such as varicella-zoster virus or recurrent bacterial infection.

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.