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

NATL

[Immunoglobulin for Stiff Person Syndrome]

These criteria apply to requests for use of immunoglobulins for the indication of Stiff Person Syndrome 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 Stiff Man Syndrome (also known as Moersch-Woltmann syndrome)
    AND
    • Presence of Anti-GAD antibody
    AND
    • Failure or clinically significant adverse effects to benzodiazepines (i.e., diazepam) or baclofen (oral or intrathecal)
  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.
  4. General Information:
    • Paraneoplastic Stiff-man syndrome (also known as Moersch-Woltmann syndrome) is a rare progressive neurological disorder characterized by progressive rigidity and stiffness of the axial musculature, associated with painful spasms, primarily in the lower limbs, neck and trunk.
    • Symptoms are related to autoantibodies directed against glutamic acid decarboxylase in the nervous system called anti-GAD antibodies. This antibody marker, which is an antibody to an enzyme found both in the pancreas and in nerve tissue, is found in high concentrations in classical Stiff-man syndrome.
    • In most cases, improvement in symptoms occurs with combinations of diazepam and baclofen, often in reasonably high dosage. Where all drug treatments fail to give sufficient relief from spasms and pain, treatment is directed against the underlying immunologic condition with drug choices consisting of steroids (either intravenous or orally), plasma exchange or pooled IVIG.
    • Current treatments do not offer or lead to a cure. However, they are able to control symptoms in the majority of patients.
    • Black Box Warning: Thrombosis, renal dysfunction, acute renal failure, osmotic nephrosis, and death may occur.
  5. Therapeutic Alternatives:
    Drug Dosing Regimen Dose Limit/ Maximum Dose

    diazepam (ValiumR)

    20 to 60 mg/day PO (given in divided doses)

    Daily doses needed to control the disease can be as high as 200 to 300 mg/day in some patients

    baclofen (LioresalR)

    20 mg PO BID or TID or via intrathecal route

    80 mg/day

    * Requires Prior Authorization
  6. Recommended Dosing Regimen and Authorization Limit:
    Drug Dosing Regimen Authorization Limit
    (IVIG) Bivigam, Gammaplex Flebogamma, Gammagard, Gammagard S/D, Gammaked, Gamunex-C, Octagam,
    Cariumune NF
    2 g/kg total dose administered over 2-5 days:
    0.4 g/kg IV QD for 5 days
    OR
    1 g/kg IV QD for 2 days

    6 months or to member's renewal period, whichever is sooner

  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 bottles
    Flebogamma: 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 vialsGamunex-C: 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
    Octagam: 5% (50 mg/mL) in 20 mL, 50 mL, 100 mL, 200 mL, 500 mL
    Octagam: 10% (50 mg/mL) in 20 mL, 50 mL, 100 mL, 200 mL
    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% (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 03, 2015.
    2. Immune Globulin. American Hospital Formulary Service Drug Information. Available at: http://www.medicinescomplete.com/mc/ahfs/current/. Accessed June 03, 2015.
    3. Gammagard-SD [Prescribing Information], Westlake Village, CA; Baxter: September 2013.
    4. Gammaplex [Prescribing Information]. BPL inc, Releigh, NC; 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], CSL Behring AG, August 2013.
    8. Privigen [Prescribing Information], CSL Behring AG, November 2013.
    9. Gammagard Liquid [Prescribing Information], Westlake Village, CA; Baxter: September 2013.
    10. HyQvia [Prescribing Information]. Westlake Village, CA; Baxter: September 2014.
    11. Elovaara I, Apostolski S, van Doorn P, et al. EFNS guidelines for the use of intravenous immunoglobulin in treatment of neurological diseases: EFNS task force on the use of intravenous immunoglobulin in treatment of neurological diseases. Eur J Neurol. 2008 Sep;15(9):893-908.
    12. Gnanapavan S, Vincent A, Giovannoni G. Surviving stiff-person syndrome: a case report. J Neurol. 2011 Oct;258(10):1898-900.
    13. Helfgott SM. Stiff-person syndrome. UpToDate. July 14, 2014.
    14. Bivigam [Prescribing Information], Boca Raton, FL : Biotest Pharmaceuticals Corp.; April 2014.
    15. Flebogamma [Prescribing Information],Barcelona, Spain; Institutio Grifols, S.A.; September 2013.
    16. Gammaked [Prescribing Information], Research Triangle Park, NC; Grifolis Therapeutics Inc.; September 2013.
    17. Octagam 5% [Prescribing Information], Hoboken, NJ: Octapharma USA; October 2013.
    18. Octagam 10% [Prescribing Information], Hoboken, NJ: Octapharma USA; July 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 JB
Approved By Health Net National P&T: 20-FEB-13, 20-NOV-13, 19-NOV-14, 18-NOV-15
Revised: 15-JUN-13 SR, 14-JUL-14 DD, 23-FEB-15 DM, 03-JUN-15 HG