BlueCross BlueShield of Tennessee Medical Policy Manual

Intravenous Immune Globulin (IVIG) Therapy

DESCRIPTION

Immune globulins or immunoglobulins (Ig) are specialized glycoproteins which function in the body as antibodies in the immune system.  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.  It has multiple functions including placental antibody transfer, phagocytic cell surface binding and the activation of 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, Flebogamma® 5% DIF, Gammagard® Liquid, Gammagard® S/D, Gammaplex® 5% Liquid, Gamunex®-C, Octagam® 5% and Privigen®.

REFER TO DECISION SUPPORT TREE

POLICY

    • Alopecia universalis

    • Myocarditis

    • Anemia

    • Myositis

    • Antiphospholipid antibody syndrome (APS)

    • Necrotizing fasciitis

    • Aplasia, pure red cell

    • Neonatal jaundice

    • Asthma

    • Neuropathy

    • Autoimmune neutropenia

    • Ocular cicatricial pemphigoid

    • Behçet's syndrome

    • Opsoclonus-myoclonus

    • Birdshot retinopathy

    • Otitis media

    • Bullous pemphigoid

    • Paraneoplastic pemphigus

    • Burns

    • Paraneoplastic visual loss

    • Chronic fatigue syndrome

    • Pemphigus gestationis

    • Clostridium induced colitis

    • Polymyositis

    • Crohn's disease

    • Polyradiculoneuropathy other than CIDP

    • Cutaneous polyarteritis nodosa

    • Post transplant lymphoproliferative disorder

    • Cystic fibrosis

    • Posttransfusion purpura

    • Diabetic amyotrophy

    • Pyoderma gangrenous

    • Encephalomyelitis - acute, disseminated

    • Recurrent fetal loss

    • Epidermolysis bullosa acquisita

    • Refractory to platelet transfusion

    • Epilepsy

    • Respiratory syncytial virus

    • Epstein-Barr induced cerebellar ataxia
    • Rheumatoid arthritis

    • Hemolytic uremic syndrome

    • Stevens-Johnson syndrome

    • Hemophagocytic syndrome

    • Stiff person syndrome

    • Hemophilia

    • Still's disease

    • Hopkins' syndrome

    • Systemic lupus erythematosus (SLE)

    • In vitro fertilization

    • Systemic vasculitis

    • Isaac's syndrome

    • Thrombocytopenia, antenatal and neonatal

    • Juvenile rheumatoid arthritis

    • Thrombocytopenia, nonimmune

    • Leukocytoclastic vasculitis

    • Thrombocytopenia, quinine-induced

    • Linear immunoglobulin - A disease

    • Thrombocytopenia, septic

    • Lysinuric protein intolerance

    • Thrombotic thrombocytopenic purpura

    • Malaria

    • Uveitis

    • Multiple myeloma

    • Von Willebrand's syndrome

 
    • Wegener's granulomatosis

See also:

MEDICAL APPROPRIATENESS

APPLICABLE TENNESSEE STATE MANDATE REQUIREMENTS

BlueCross BlueShield of Tennessee’s Medical Policy complies with Tennessee Code Annotated Section 56-7-2352 regarding coverage of off-label indications of Food and Drug Administration (FDA) approved drugs when the off-label use is recognized in one of the statutorily recognized standard reference compendia or in the published peer-reviewed medical literature.

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).

Intravenous immune globulin therapy has been used for multiple off-label uses, however no controlled studies were found in the published literature that validate its use in the treatment/prevention of any other conditions/diseases.

SOURCES

BlueCross BlueShield Association. Medical Policy Reference Manual. (10:2011). Immune Globulin Therapy (8.01.05). Retrieved December 14, 2012 from BlueWeb.

Center for Disease Control. (2012, October). ACIP Provisional Recommendations. Prevention of measles, rubella, congenital rubella syndrome (CRS), and mumps. Retrieved January 30, 2013 from http://www.cdc.gov/vaccines/recs/provisional/default.htm.

Lexi-Comp Online. (2012, November). AHFS DI. Immune globulin. Retrieved November 13, 2012 from Lexi-Comp Online with AHFS.

MICROMEDEX Healthcare Series. Drugdex Evaluations. (2012, October). Immune Globulin. Retrieved December 13, 2012 from MICROMEDEX Healthcare Series.

Octapharma.(2009, September). Octagam® [immune globulin intravenous (human)]. Retrieved February 1, 2013 from http://www.octapharma.com/index.php?eID=tx_nawsecuredl&u=0&file=uploads/media/Octagam_5__SPC_for_USA_02.pdf&t=1359830444&hash=c04d0a2c8be95492b9c2222256735a5fb43d9f1d.

U. S. Food and Drug Administration.  (2010, January). Gammagard® S/D immune globulin intravenous (human). Retrieved November 13, 2012 from http://www.fda.gov/downloads/BiologicsBloodVaccines/BloodBloodProducts/ApprovedProducts/LicensedProductsBLAs/FractionatedPlasmaProducts/UCM197905.pdf.

U. S. Food and Drug Administration. (2007, July). Center for Biologics Evaluation and Research. Privigen, Immune Globulin Intravenous (Human), 10% Liquid  Retrieved November 13, 2012 from http://www.fda.gov/downloads/BiologicsBloodVaccines/BloodBloodProducts/ApprovedProducts/LicensedProductsBLAs/FractionatedPlasmaProducts/UCM303092.pdf.

U. S. Food and Drug Administration. (2008, October). Center for Biologics Evaluation and Research. Carimune® NF, Nanofiltered: Immune Globulin Intravenous (Human). Retrieved November 13, 2012 from http://www.fda.gov/downloads/BiologicsBloodVaccines/UCM152763.pdf.

U. S. Food and Drug Administration. (2009, February). Center for Biologics Evaluation and Research. Gamunex®-C, [Immune Globulin Injection (Human). Retrieved November 13, 2012 from  http://www.fda.gov/downloads/BiologicsBloodVaccines/BloodBloodProducts/ApprovedProducts/LicensedProductsBLAs/FractionatedPlasmaProducts/UCM069968.pdf.

U. S. Food and Drug Administration. (2009, September). Center for Biologics Evaluation and Research. Gammaplex Immune Globulin Intravenous (Human), 5% Liquid. Retrieved November 13, 2012 from http://www.fda.gov/downloads/BiologicsBloodVaccines/BloodBloodProducts/ApprovedProducts/LicensedProductsBLAs/FractionatedPlasmaProducts/UCM182963.pdf.

U. S. Food and Drug Administration. (2012, January). Center for Biologics Evaluation and Research. Flebogamma 5% dif. Retrieved November 13, 2012 from http://www.fda.gov/downloads/BiologicsBloodVaccines/BloodBloodProducts/ApprovedProducts/LicensedProductsBLAs/FractionatedPlasmaProducts/UCM172599.pdf.

U. S. Food and Drug Administration. (2012, January). Center for Biologics Evaluation and Research. Flebogamma 10% dif. Retrieved November 13, 2012 from http://www.fda.gov/downloads/BiologicsBloodVaccines/BloodBloodProducts/ApprovedProducts/LicensedProductsBLAs/FractionatedPlasmaProducts/UCM296138.pdf.

U. S. Food and Drug Administration. (2012, June). Center for Biologics Evaluation and Research. Gammagard® Liquid immune globulin intravenous (human). Retrieved November 13, 2012 from http://www.fda.gov/downloads/BiologicsBloodVaccines/BloodBloodProducts/ApprovedProducts/LicensedProductsBLAs/FractionatedPlasmaProducts/UCM070010.pdf.

U. S. Food and Drug Administration. (2012, June). Center for Biologics Evaluation and Research. Gammagard® Liquid immune globulin intravenous (human)approval letter. Retrieved January 29, 2013 from http://www.fda.gov/BiologicsBloodVaccines/BloodBloodProducts/ApprovedProducts/LicensedProductsBLAs/FractionatedPlasmaProducts/ucm311670.htm.

ORIGINAL EFFECTIVE DATE:  12/4/1997

MOST RECENT REVIEW DATE:  7/13/2013

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, Flebogamma® 5% DIF, Gammagard® Liquid, Gammagard® S/D, Gammaplex® 5% Liquid, Gamunex®-C, Octagam® 5% and Privigen®)

  1. Is the requested medication being used to treat ANY ONE of the following?

    • Alopecia universalis

    • Myocarditis

    • Anemia

    • Myositis

    • Antiphospholipid antibody syndrome (APS)

    • Necrotizing fasciitis

    • Aplasia, pure red cell

    • Neonatal jaundice

    • Asthma

    • Neuropathy

    • Autoimmune neutropenia

    • Ocular cicatricial pemphigoid

    • Behçet's syndrome

    • Opsoclonus-myoclonus

    • Birdshot retinopathy

    • Otitis media

    • Bullous pemphigoid

    • Paraneoplastic pemphigus

    • Burns

    • Paraneoplastic visual loss

    • Chronic fatigue syndrome

    • Pemphigus gestationis

    • Clostridium induced colitis

    • Polymyositis

    • Crohn's disease

    • Polyradiculoneuropathy other than CIDP

    • Cutaneous polyarteritis nodosa

    • Post transplant lymphoproliferative disorder

    • Cystic fibrosis

    • Posttransfusion purpura

    • Diabetic amyotrophy

    • Pyoderma gangrenous

    • Encephalomyelitis - acute, disseminated

    • Recurrent fetal loss

    • Epidermolysis bullosa acquisita

    • Refractory to platelet transfusion

    • Epilepsy

    • Respiratory syncytial virus

    • Epstein-Barr induced cerebellar ataxia
    • Rheumatoid arthritis

    • Hemolytic uremic syndrome

    • Stevens-Johnson syndrome

    • Hemophagocytic syndrome

    • Stiff person syndrome

    • Hemophilia

    • Still's disease

    • Hopkins' syndrome

    • Systemic lupus erythematosus (SLE)

    • In vitro fertilization

    • Systemic vasculitis

    • Isaac's syndrome

    • Thrombocytopenia, antenatal and neonatal

    • Juvenile rheumatoid arthritis

    • Thrombocytopenia, nonimmune

    • Leukocytoclastic vasculitis

    • Thrombocytopenia, quinine-induced

    • Linear immunoglobulin - A disease

    • Thrombocytopenia, septic

    • Lysinuric protein intolerance

    • Thrombotic thrombocytopenic purpura

    • Malaria

    • Uveitis

    • Multiple myeloma

    • Von Willebrand's syndrome

 
    • Wegener's granulomatosis

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

If no, go to question #2

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

If yes, this satisfies medical necessity and medical appropriateness criteria

If no, go to question #3

  1. Does the individual have a diagnosis of autoimmune mucocutaneous blistering disease (e.g., pemphigus vulgaris, pemphigus foliaceus) proven by biopsy?

If yes, this satisfies medical necessity and medical appropriateness criteria

If no, go to question #4

  1. Is the individual a neonate requesting adjunctive treatment (to increase efficacy of a primary treatment regimen)?

If yes, this satisfies medical necessity and medical appropriateness criteria

If no, go to question #5

  1. Does the individual have a diagnosis of dermatomyositis with failure of initial treatment and corticosteroid therapy is contraindicated or ineffective due to proven resistance?

If yes, this satisfies medical necessity and medical appropriateness criteria

If no, go to question #6

  1. Does the individual have a diagnosis of Guillain-Barré syndrome (GBS) with ALL of the following?

If yes, this satisfies medical necessity and medical appropriateness criteria

If no, go to question #7

  1. Does the individual have a diagnosis of Immune/idiopathic thrombocytic purpura (ITP) and a rapid rise in platelets is required for ANY ONE of the following?

If yes, this satisfies medical necessity and medical appropriateness criteria

If no, go to question #8

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

If yes, this satisfies medical necessity and medical appropriateness criteria

If no, go to question #9

  1. Does the individual have a diagnosis of multifocal motor neuropathy (MMN) and treatment is as second-line therapy (i.e., after failure of initial treatment of choice)?

If yes, this satisfies medical necessity and medical appropriateness criteria

If no, go to question #10

  1. Does the individual have a diagnosis of relapsing-remitting multiple sclerosis and treatment is second-line therapy?

If yes, this satisfies medical necessity and medical appropriateness criteria

If no, go to question #11

  1. Does the individual have a diagnosis of myasthenia gravis with ANY ONE of the following?

If yes, this satisfies medical necessity and medical appropriateness criteria

If no, go to question #12

  1. 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

  1. Does the individual have a diagnosis of toxic shock syndrome and is severely ill with ANY ONE of the following?

If yes, go to question #14

If no, go to question #15

  1. Will treatment be adjunctive?

If yes, this satisfies medical necessity and medical appropriateness criteria

If no, this does not satisfy medical necessity and medical appropriateness criteria

  1. Is the individual a transplant recipient with ANY ONE of the following?

If yes, this satisfies medical necessity and medical appropriateness criteria

If no, go to question #16

  1. Is the request for prevention of bacterial infections associated with ANY ONE of the following?

If yes, this satisfies medical necessity and medical appropriateness criteria

If no, go to question #17

  1. Is the request to prevent graft-versus-host disease (GVHD) associated with ANY ONE of the following and treatment is adjunctive?

If yes, this satisfies medical necessity and medical appropriateness criteria

If no, go to question #18

  1. Is the request to prevent measles postexposure for ANY ONE of the following?

If yes, this satisfies medical necessity and medical appropriateness criteria

If no, go to question #19

  1. Is the request to prevent varicella postexposure when varicella-zoster immune globulin is unavailable?

If yes, this satisfies medical necessity and medical appropriateness criteria

If no, this does not satisfy medical necessity and medical appropriateness criteria

This document has been classified as public information.