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Prior Authorization Protocol
BIVIGAMTM, CARIMUNE NFR, FLEBOGAMMA DIFR, GAMMAGARD LIQUIDR, GAMMAGARD S/DR, GAMMAKEDR, GAMMAPLEXTM, GAMUNEX-CR,OCTAGAMR, PRIVIGENR , HIZENTRATM, HYQVIA

NATL

[Immunoglobulin for Multiple Sclerosis]

These criteria apply to requests for use of immunoglobulins for the indication of Multiple Sclerosis only. For the use of immunoglobulins for any other indication, please refer to the appropriate indication specific criteria.
Coverage of drugs is first determined by the member’s pharmacy or medical benefit. Please consult with or refer to the Evidence of Coverage document.
  1. FDA Approved Indications:
    • For immune globulin intravenous (IVIG) (including Gamunex-C, Gammaked and Gammagard when used intravenously)
      • Replacement therapy for primary immunodeficiency (PI) This includes, but is not limited to, congenital agammaglobulinemia, common variable immunodeficiency, X-linked agammaglobulinemia, Wiskott-Aldrich syndrome, and severe combined immunodeficiencies.
      • Treatment of patients with idiopathic thrombocytopenic purpura (ITP) to raise platelet counts to prevent bleeding or to allow a patient with ITP to undergo surgery.
      • Maintenance therapy to improve muscle strength and disability in adult patients with Multifocal Motor Neuropathy (MMN).
      • Prevention of bacterial infections in patients with hypogammaglobulinemia and/or recurrent bacterial infections associated with B-cell chronic lymphocytic leukemia (CLL).
      • Prevention of coronary artery aneurysms associated with Kawasaki syndrome.
      • Treatment of chronic inflammatory demyelinating polyneuropathy (CIDP) to improve neuromuscular disability and impairment and for maintenance therapy to prevent relapse.
    • For immune globulin subcutaneous (including Gamunex-C, Gammaked, Gammagard Liquid, Hizentra, and Hyqvia when used subcutaneously)
      • Treatment of/replacement therapy for patients with primary immunodeficiency (PI). This includes, but is not limited to, congenital agammaglobulinemia, common variable immunodeficiency (CVID), X-linked agammaglobulinemia, Wiskott-Aldrich syndrome, and severe combined immunodeficiencies.
  2. Health Net Approved Indications and Usage Guidelines:

    Diagnosis of relapsing remitting multiple sclerosis (MS) as defined by all of the following Posner criteria:

    • Onset of symptoms between 10 and 50 years of age
    AND
    • There is a consistent course of relapsing/remitting type of MS with objective evidence of at least 2 attacks (also known as an exacerbation, flare, or relapse) within the last year clinically defined as the sudden appearance or worsening of an MS symptom or symptoms
    AND
    • Each attack lasts at least 24 hours
    AND
    • Evidence of inflammation and/or damage in different areas of the central nervous system
    AND
    • Attacks separated by at least 1 month
    AND
    • Documented neurologic signs of lesions on MRIs in more than one area of the brain or spinal cord white matter
    AND
    • Patient has severely impaired function secondary to relapsing-remitting MS as measured by a standard clinical scale
    AND
    • Failure or clinically significant adverse effect or patient is refractory to at least a three month trial (at therapeutic doses) of other standard therapies [i.e., Avonex, Aubagio, Betaseron, Rebif, Copaxone, Tecfidera, or Gilenya]

    AND

    • There must be no other explanation for these attacks or the symptoms the person is experiencing.
  3. Coverage is Not Authorized For:
    • Non-FDA approved indications, which are not listed in the Health Net Approved Indications and Usage Guidelines section, unless there is sufficient documentation of efficacy and safety in the published literature.
    • A list of specific indications for which coverage is not authorized may be found in the PA guideline: Immunoglobulin Conditions Not Medically Necessary - NATL
    • Health Net does not consider IVIG therapy to be appropriate for the routine use of IVIG to treat multiple sclerosis.
  4. General Information:
    • The clinical course of MS usually falls within one of the following categories, with the potential for progression from one pattern to a more serious one:
      • Relapsing-remitting MS: This form of MS is characterized by clearly defined acute attacks with full recovery or with some remaining neurological signs/symptoms and residual deficit upon recovery. The periods between disease relapses are characterized by a lack of disease progression.
      • Secondary progressive MS: The disease begins with an initial relapsing-remitting course, followed by progression at a variable rate that may also include occasional relapses and minor remissions.
      • Progressive-relapsing MS: Persons with progressive-relapsing MS experience progressive disease from onset, with clear, acute relapses that may or may not resolve with full recovery. Unlike relapsing-remitting MS, the periods between relapses are characterized by continuing disease progression.
      • Primary progressive MS: The disease shows gradual progression of disability from its onset, without plateaus or remissions or with occasional plateaus and temporary minor improvements.
  5. Therapeutic Alternatives:
    Drug Dosing Regimen Dose Limit/ Maximum Dose

    AvonexR (interferon Beta-1a)*

    30 mcg IM Q Wk
    Avonex may be titrated to reduce the incidence of flu-like symptoms,
    starting with 7.5 mcg for the first week and increasing the dose by 7.5 mcg each week
    for the next 3 weeks until the recommended dose of 30 mcg Q Wk is obtained.

    30 mcg Q Wk

    RebifR (interferon Beta-1a)*

    22 mcg or 44 mcg SC TIW titrated over a 4 week period.

    44 mcg TIW

    BetaseronR (interferon Beta -1b)*
    ExtaviaTM (interferon Beta-1b)*

    250 mcg SC QOD.
    Generally, start at 0.0625 mg (0.25 mL) SC QOD,
    and increase over a six week period to 0.25 mg (1 mL) SC QOD.

    250 mcg QOD

    CopaxoneR (glatiramer acetate) *

    20 mg QD or 40 mg TIW
    For SC injection only, doses are not interchangeable
    20 mg QD or 40 mg TIW

    AubagioR (teriflunomide) *

    7 mg or 14 mg PO QD

    14 mg QD

    GilenyaTM (fingolimod)*

    0.5 mg PO QD

    0.5 mg QD

    TecfideraTM (dimethyl fumarate)

    120 mg PO BID for 7 days followed by 240 mg PO BID
    Administration with food may reduce the incidence of flushing
    240 mg BID

    Plegridy (peginterferon beta-1a)

    125 mcg SC every 14 days
    Dose should be titrated, starting with 63 mcg SC on day 1, 94 mcg SC on day 15, 125 mcg (full dose) SC on day 29

    125 mcg Q 2 Wk

    * Requires Prior Authorization
  6. Recommended Dosing Regimen and Authorization Limit:
    Drug Dosing Regimen Authorization Limit

    IVIG (Various Brand names)

    Relapsing Remitting Multiple Sclerosis
    2 g/kg followed by 0.4 g/kg bimonthly
    OR
    1 g/kg QD for 2 days at 4-week intervals for 6 months
    OR
    0.2 g/kg Q month for 2 years
    OR
    400 mg/kg x 5 days, followed by 0.4 g/kg Q 2 months for 2 years
    6 months or to member's renewal period, whichever is longer.

    Further approval will be considered upon receipt of chart documentation of clinical improvement (fewer relapses and/or improvement in level of disability).
  7. Product Availability:
    Intravenous Immunoglobulin
    Bivigam: 10% (1 g/10 mL) in 50 mL, 100 mL vials
    Carimune NF powder for injection: 3 g, 6 g, 12 g vials
    Flebogamma DIF: 5% (50 mg/mL) in 10 mL, 50 mL, 100 mL, 200 mL, 400 mL vials; 10% (5 g/50 mL) in 50 mL, 100 mL, 200 mL vials
    Gammagard: 10% (1 g/10 mL) in 10 mL, 25 mL, 50 mL, 100 mL, 200 mL, 300 mL vials
    Gammagard S/D powder for injection: 2.5 g, 5 g, 10 g bottles
    Gammaked: 10% (1 g/10 mL) in 10 mL, 25 mL, 50 mL, 100 mL, 200 mL vials
    Gammaplex: 5% (50 mg/mL) in 50 mL, 100 mL, 200 mL, 400 mL vials
    Gamunex-C: 10% (1 g/10 mL) in 10 mL, 25 mL, 50 mL, 100 mL, 200 mL, 400 ml vials
    Octagam: 5% (50 mg/mL) in 20 mL, 50 mL, 100 mL, 200 mL, 500 mL
    Octagam: 10% (100 mg/mL) in 20 mL, 50 mL, 100 mL, 200 mL bottles
    Privigen: 10% (100 mg/mL) in 50 mL, 100 mL, 200 mL, 400 mL vials
    Subcutaneous Immunoglobulin
    Gammagard: 10% (1 g/10 mL) in 10 mL, 25 mL, 50 mL, 100 mL, 200 mL, 300 mL vials
    Gammaked: 10% (1 g/10 mL) in 10 mL, 25 mL, 50 mL, 100 mL, 200 mL vials
    Gamunex-C: 10% (1 g/10 mL) in 10 mL, 25 mL, 50 mL, 100 mL, 200 mL, 400 ml vials
    Hizentra protein solution for subcutaneous injection: 20% (0.2 g/mL) in 5 mL, 10 mL, 20 mL, 50 mL vials
    HyQvia: 10% IgG (1 g/10 mL) in 25 mL, 50 mL, 100 mL, 200 mL, 300 mL vials
    and 160 U/mL recombinant human hyaluronidase in 1.25 mL, 2.5 mL, 5 mL, 10 mL, 15 mL vials
  8. References:
    1. MicromedexR Healthcare Series [Internet database]. Greenwood Village, Colo: Thomson Healthcare. Updated periodically. Accessed June 1, 2015.
    2. Immune Globulin. American Hospital Formulary Service Drug Information. Available at: http://www.medicinescomplete.com/mc/ahfs/current/. Accessed June 1, 2015.
    3. Gammagard-SD [Prescribing Information], Westlake Village, CA; Baxter: September 2013.
    4. Gammaplex [Prescribing Information], United Kingdom ; Bio Products Laboratory Ltd. September 2013.
    5. Gamunex-C [Prescribing Information]. Research Triangle Park, NC. Grifolis Therapeutics Inc: July 2014.
    6. Hizentra [Prescribing Information], Bern, Switzerland; CSL Behring AG, January 2015.
    7. Carimune [Prescribing Information], Bern, Switzerland ; CSL Behring AG, September 2013.
    8. Privigen [Prescribing Information], Bern, Switzerland ; CSL Behring AG, November 2013.
    9. Gammagard Liquid [Prescribing Information], Westlake Village, CA; Baxter: April 2014.
    10. Buttmann M, Rieckmann P. Treating multiple sclerosis with monoclonal antibodies. Expert Rev Neurother. 2008 Mar;8(3):433-55
    11. Zohren F, Toutzaris D, Kldrner V, et al. The monoclonal anti-VLA-4 antibody natalizumab mobilizes CD34+ hematopoietic progenitor cells in humans. Blood. 2008 Apr 1;111(7):3893-5.
    12. Clerico M, Rivoiro C, Contessa G, et al. The therapy of multiple sclerosis with immune-modulating or immunosuppressive drug A critical evaluation based upon evidence based parameters and published systematic reviews. Clin Neurol Neurosurg. 2007 Dec 27;
    13. Fiore D. Multiple sclerosis and Natalizumab. Am J Ther. 2007 Nov-Dec;14(6):555-60.
    14. Engelhardt B, Kappos L. Natalizumab: targeting alpha4-integrins in multiple sclerosis. Neurodegener Dis. 2008;5(1):16-22.
    15. Mareckova H, Havrdova E, Krasulova E, et al. Natalizumab in the treatment of patients with multiple sclerosis: first experience. Ann N Y Acad Sci. 2007 Sep;1110:465-73.
    16. Horga A, Horga de la Parte JF. Natalizumab in the treatment of multiple sclerosis. Rev Neurol. 2007 Sep 1-15;45(5):293-303.
    17. Greenberg BM, Balcer L, Calabresi PA, et al. Interferon Beta Use and Disability Prevention in Relapsing-Remitting Multiple Sclerosis. Arch Neurol. 2012 Nov 5:1-4.
    18. Miller AE, Rhoades RW. Treatment of relapsing-remitting multiple sclerosis: current approaches and unmet needs. Curr Opin Neurol. 2012 Feb;25 Suppl:S4-10
    19. Flebogamma [Prescribing Information], Barcelona, Spain; Institutio Grifols, S.A: September 2013.
    20. Gammaked [Prescribing Information], Research Triangle Park, NC; Grifolis Therapeutics Inc; : September 2013.
    21. Octagam 5% [Prescribing Information]. Hoboken, NJ; Octapharmac USA: October 2013.
    22. Bivigam [Prescribing Information], Boca Raton, FL; Biotest Pharmaceuticals Corp: May 2015
    23. Octagam 10% [Prescribing Information]. Hoboken, NJ; Octapharma USA: December 2014.
    24. HyQvia [Prescribing Information]. Westlake Village, CA; Baxter: September 2014.
The material provided to you are guidelines used by this plan to authorize, modify or determine coverage for persons with similar illnesses or conditions. Specific care and treatment may vary depending on individual need and the benefits covered under your contract.
Draft Prepared: 05-DEC-12 MJM
Approved By Health Net National P&T: 20-FEB-13, 20-NOV-13, 19-NOV-14, 18-NOV-15
Revised: 15-JUN-13 SR, 02-JUL-14 MH, 23-FEB-15 DM, 04-JUN-15 SM