For the purpose of this policy, the criteria below apply to plans that have elected to use Aetna Pharmacy to manage the fulfillment and the precertification of specialty drugs.
Under some plans, including plans that use an open or closed formulary, Intravenous Immunoglobulins (IVIG) and Adagen are subject to Precertification. If Precertification requirements apply Aetna considers these medications to be medically necessary for those members who meet the following precertification criteria: (see also Appendix A)
A documented diagnosis of adenosine deaminase deficiency (ADA) in patients with severe combined immunodeficiency disease (SCID) AND
The patient is not a candidate or has failed a bone marrow transplantation
For all intravenous immunoglobulin (IVIG) products
Aetna considers the use of intravenous immunoglobulin (IVIG) therapy medically necessary in members with the conditions specified below:
Acquired red cell aplasia
Acute disseminated encephalomyelitis (see Appendix)
Autoimmune mucocutaneous blistering diseases: IVIG is considered medically necessary for members with pemphigus vulgaris, pemphigus foliaceus, bullous pemphigoid, mucous membrane pemphigoid (a.k.a., cicatrical pemphigoid), gestational pemphigoid, linear IgA disease,and epidermolysis bullosa acquisita if the member has either failed or has contraindications to conventional therapy, or the member has rapidly progressive disease in which a clinical response could not be affected quickly enough using conventional agents. When indicated for rapidly progressive disease, accepted guidelines indicate that IVIG should be given along with conventional treatment(s) and IVIG should be used only until conventional therapy could take effect. (See Appendix) Note: IVIG for the treatment of autoimmune mucocutaneous blistering disease is considered medically necessary only for short-term therapy and not as a maintenance therapy
Autoimmune neutropenia, refractory (see appendix)
B-cell chronic lymphocytic leukemia (CLL): for persons with hypogammaglobulinemia associated with CLL and recurrent infections or specific antibody deficiency (see Appendix)
Birdshot (vitiligenous) retinochoroidopathy (see Appendix)
Chronic inflammatory demyelinating polyneuropathy (see Appendix)
Churg-Strauss Syndrome (CSS) (allergic granulomatosis), for persons with severe active illness for whom other interventions have been unsuccessful, have become intolerable, or are contraindicated
Dermatomyositis in persons who are resistant to first and second line therapies (see Appendix)
Enteroviral meningoencephalitis (see appendix)
Guillain-Barré syndrome (GBS) and GBS variants: IVIG is generally accepted as the treatment of choice for persons with Guillain-Barre syndrome, provided that they are so severely affected that they at least require aid to walk, that the disorder is diagnosed during the first 2 weeks of the illness, and that there are no contraindications to IVIG (see appendix)
Hemolytic disease of newborn, to decrease need for exchange transfusion (see appendix)
HIV infected children: bacterial control or prevention (see appendix)
HIV-associated thrombocytopenia, pediatric or adult: considered medically necessary when criteria in Appendix are met (see Appendix)
Hyperimmunoglobulinemia E syndrome, for treatment of severe eczema (see appendix)
Immune or idiopathic thrombocytopenic purpura (ITP) when a rapid rise in the platelet count is required, such as prior to surgery, to control excessive bleeding, or to defer or avoid splenectomy (see Appendix for criteria for ITP in adults, ITP in children, chronic ITP, and ITP in pregnancy)
Kawasaki disease (see Appendix)
Lambert-Eaton myasthenic syndrome (see Appendix)
Moersch-Woltmann (Stiff-man) syndrome (unresponsive to other therapies) (see Appendix)
Multifocal motor neuropathy: for persons who have progressive, symptomatic multifocal motor neuropathy that has been diagnosed on the basis of electrophysiologic findings that rule out other possible conditions that may not respond to this treatment (see Appendix) 2
Multiple myeloma (see Appendix)
Myasthenia gravis (see Appendix)
Neonatal alloimmune thrombocytopenia (NAIT) (also known as fetal alloimmune thrombocytopenia or FAIT) (see Appendix)
Neonatal hemochromatosis, prophylaxis (see Appendix)
Neonatal sepsis, treatment (see Appendix)
Opsoclonus-myoclonus (see Appendix)
Paraneoplastic opsoclonus-myoclonus-ataxia associated with neuroblastoma (see Appendix)
Parvovirus B19 infection, chronic, with severe anemia (see Appendix)
Polymyositis in persons who are resistant to first and second line therapies (see Appendix)
Post-transfusion purpura (see Appendix)
Preparation for Thymoma surgery to prevent myasthenic exacerbation
Primary humoral immunodeficiency diseases (such as congenital agammaglobulinemia (X-linked agammaglobulinemia), hypogammaglobulinemia, common variable immunodeficiency, X-linked immunodeficiency with hyperimmunoglobulin M, Wiscott-Aldrich syndrome, and severe combined immunodeficiency) (see Appendix)
Rasmussen encephalitis (Rasmussen's syndrome) (see Appendix)
Refractory autoimmune hemolytic anemia (see Appendix)
Relapsing-remitting multiple sclerosis (MS) when standard approaches (i.e., interferons) have failed, become intolerable, or are contraindicated (see Appendix) (See also CPB 264 - Multiple Sclerosis)
Renal transplantation from live donor with ABO incompatibility or positive cross-match, where a suitable non-reactive live or cadaveric donor is unavailable (preparative regimen)
Secondary immunosuppression associated with major surgery (such as cardiac transplants) and certain diseases (hematologic malignancies, extensive burns, or collagen-vascular diseases) (see Appendix)
Selective IgG subclass deficiencies with severe infection for persons meeting selection criteria (see Appendix)
Solid organ transplantation, for allosensitized members undergoing solid organ transplant (see appendix)
Staphylococcal toxic shock syndrome (see Appendix)
Stem cell or bone marrow transplantation: IVIG is indicated for prophylaxis in allogeneic or syngeneic transplant recipients within the first 100 days post-transplant; after 100 days post-transplant IVIG is indicated for recipients who are markedly hypogammaglobinemic (IgG level less than 400 mg/dL), or who have CMV, EBV, or RSV infection (see Appendix and CPB 544 - Immune Globulins for Post-exposure Prophylaxis). IVIG is also indicated for steroid-resistant graft-versus-host disease in bone marrow transplant recipients 20 years of age or older, in the first 100 days post transplant, and who are hypogammaglobinemic (IgG level less than 400 mg/dL).
Systemic lupus erythematosus (SLE), for persons with severe active SLE for whom other interventions have been unsuccessful, have become intolerable, or are contraindicated (see Appendix)
Toxic epidermal necrolysis and Steven-Johnson syndrome (see Appendix)
Toxic shock syndrome or toxic necrotizing fasciitis due to group A streptococcus (see Appendix).
Aetna considers subcutaneously administered immunoglobulins as an alternative to intravenous immunoglobulin therapy medically necessary for members who meet the criteria for IVIG set forth above.
Aetna considers intramuscularly administered immunoglobulins (e.g., GamaSTAN S/D) medically necessary as an alternative to intravenous immunoglobulin therapy for conditions associated with hypogammaglobulinemia that meet the criteria for IVIG set forth above. Intramuscular formulations of immune globulin are also considered medically necessary for the following indications: prophylaxis of hepatitis A; prevention or modification of measles (rubeola) in persons exposed fewer than 6 days previously; passive immunization against varicella in immunosuppressed patients; and prophylaxis of rubella in pregnancy when therapeutic abortion is not an option.
Aetna considers the use of IVIG experimental and investigational for all other clinical conditions. See appendix for a current list of such indications.
For information on site of service for IVIG infusions, see Utilization Management Policy on Site of Care for Specialty Drug Infusions.
The above policy is based on the following references:
1. AHFS Drug Information® with AHFSfirstReleases®. ( www.statref.com), American Society Of Health-System Pharmacists®, Bethesda, MD. Updated periodically. 2. DRUGDEX® System [Internet database]. Greenwood Village, Colo: Thomson Micromedex. Updated periodically. 3. Drug Facts and Comparisons on-line. (www.drugfacts.com), Wolters Kluwer Health, St. Louis, MO. Updated periodically. 4. PDR® Electronic Library™ [Internet database]. Greenwood Village, Colo: Thomson Micromedex. Updated periodically. 5. Siegel J. The Product: All intravenous immunoglobulins are not equivalent. Pharmacotherapy 2005;25(11 pt2):78S-84S. 6. Shah S. Pharmacy considerations for the use of IGIV therapy. Am J Health-Syst Pharmacy 2005;62:S5-S11. 7. Orange J, Hossny E, Weiler C et al. Use of intravenous immunoglobulin in human disease: A review of evidence by members of the Primary Immunodeficiency Committee of the American Academy of Allergy, Asthma and Immunology. J Allergy Clin Immunol 2006;117:S525-S53. 8. Carimune ® NF [package insert]. Kankakee (IL): CSL Behring, October 2008. 9. Flebogamma ® 5% DIF [package insert]. Los Angeles (CA): Grisfols, November 2006. 10. Gammagard® Liquid [package insert]. Westlake Village (CA): Baxter, April 2005. 11. Gammagard® S/D IgA < 1µg/ml in a 5% solution [package insert]. Westlake Village (CA): Baxter, March 2007. 12. Gammagard® S/D IgA < 2.2 µg/ml in a 5% solution [package insert]. Westlake Village (CA): Baxter, October 2008. 13. Gamunex® [package insert]. Research Triangle Park (NC): Talecris, October 2008. 14. Octagam® [package insert]. Hoboken (NJ): Octapharma, February 2009. 15. Privigen® [package insert]. Kankakee (IL): CSL Behring, June 2009. 16. Vivaglobin® [package insert]. Kankakee (IL): CSL Behring, April 2007. 17. Roifman C, Schroeder H, Berger M, et al. Comparison of the efficacy of IGIV-C, 10% (caprylate/chromatography) and IGIV-SD, 10% as replacement therapy in primary immune deficiency: a randomized double-blind trial. Int Immunopharmacol 2003;3:1325-33. 18. Bussel J, Eldor A, Kelton J et al. IGIV-C, a novel intravenous immunoglobulin: evaluation of safety, efficacy, mechanisms of action, and impact on quality of life. Thromb Haemost 2004;91:771-8. 19. Berger M. Subcutaneous immunoglobulin replacement in primary immunodeficiency. Clin Immunol. 2004;112:1-7. 20. Cuvitru [prescribing information]. Westlake Village, CA: Baxalta US Inc.; Sept. 2016.
Copyright Aetna Inc. All rights reserved. Pharmacy Clinical Policy Bulletins are developed by Aetna to assist in administering plan benefits and constitute neither offers of coverage nor medical advice. This Clinical Policy Bulletin contains only a partial, general description of plan or program benefits and does not constitute a contract. Aetna does not provide health care services and, therefore, cannot guarantee any results or outcomes. Participating providers are independent contractors in private practice and are neither employees nor agents of Aetna or its affiliates. Treating providers are solely responsible for medical advice and treatment of members. This Clinical Policy Bulletin may be updated and therefore is subject to change.