Prior Auth Protocol

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.

Health Net Approved Indications and Usage Guidelines:

Diagnosis of myasthenia gravis (MG) or Lambert Eaton myasthenic syndrome (LEMS)

AND

Failure or clinically significant adverse effects to cholinesterase inhibitors (i.e., Mestinon) or corticosteroids (i.e., prednisone)

AND

Treatment is for reversing an acute life-threatening or disabling muscle weakness defined by ONE of the following:
- Vital capacity less than 1L/min

OR

Dysphagia associated with aspiration

OR

Inability to walk 100 feet without assistance

OR

Acutely worsening disease for which rapid improvement and strength is necessary to minimize the risk for bulbar or respiratory failure

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.

General Information:

Myasthenia gravis (MG) is a disorder of neuromuscular function that is characterized by fatigue and weakness of the muscular system without atrophy or sensory deficits.
Myasthenia Crisis refers to exacerbation sufficient to endanger life, and usually involves respiratory failure in MG, therefore would not include disabled patients who are able to walk with or without assistance.
Intravenous Immunoglobulin (IVIG) has not been shown to be superior to plasmapheresis in the treatment of life-threatening myasthenia gravis.
High-dose IVIG may temporarily modify the immune system and suppress autoantibody production to improve severe myasthenia gravis symptoms. The effect of IVIG is seen typically in less than a week, and the benefit can last for three to six weeks. IVIG is used to quickly reverse an exacerbation of myasthenia.
According to the European Federation of Neurological Studies (EFNS) guidelines on the use of intravenous immunoglobulin in treatment of neurological diseases, the efficacy of IVIG has been proven acute exacerbations of myasthenia gravis and short-term treatment of severe MG (level A recommendation).
A small clinical trial conducted by Wegner and Ahmed showed that long-term IVIG was effective. This trial included six patients who were anti-AChR-Ab-positive. These patients received IVIG at a dosage of 400 mg/kg/day for 5 days then a maintenance therapy of 400 mg/kg for 1 day every 3 to 4 months. After a 2 year follow up all patients maintained a good functional status and side effects from IVIG did not increase.

Therapeutic Alternatives:

Drug	Dosing Regimen	Dose Limit/ Maximum Dose
pyridostigmine (Mestinon^R); Mestinon^R Timespan (pyridostigmine extended release)	Immediate Release tablets and syrup Average dosage, 600 mg PO QD, spaced throughout the day to provide maximum relief when maximum strength is needed; mild cases may respond to 60 to 360 mg/day Extended Release 180 to 540 mg PO QD-BID	Size and frequency of dosing must be individualized for the patient. Immediate Release 1,500 mg/day Extended Release 1,080 mg/day; doses should be at least 6 hours apart.
systemic glucocorticoid (Various - prednisone, prednisolone, or methylprednisolone	An equivalent dose of prednisone 1 mg/kg per day.	2 mg/kg/day

* Requires Prior Authorization

Recommended Dosing Regimen and Authorization Limit:

Drug	Dosing Regimen	Authorization Limit
IVIG (Various Brand names)	The total dose is 2 g/kg, usually in five consecutive 0.4 g/kg daily infusions	6 months or to member's renewal period, whichever is longer. Consideration for an additional 6 months approval will be made upon receipt of chart note documentation of the patient's response to IVIG therapy.

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 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 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 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

References:

Micromedex^R Healthcare Series [Internet database]. Greenwood Village, Colo: Thomson Healthcare. Updated periodically. Accessed July 10, 2014.
Immune Globulin. American Hospital Formulary Service Drug Information. Available at: http://www.medicinescomplete.com/mc/ahfs/current/. Accessed July 9, 2013.
Gammagard-S/D [package insert], Westlake Village, CA; Baxter: December 2010.
Gammaplex [package insert]. Elstree, Herts, UK. ; Bio Products Laboratory Limited: June 2014.
Gamunex-C [package insert]. Research Triangle Park, NC. Grifolis Therapeutics Inc.: July 2014.
Hizentra [package insert], Bern, Switzerland; CSL Behring AG, January 2015.
Carimune [package insert], CSL Behring AG, September 2013.
Privigen [package insert], CSL Behring AG, November 2013.
Gammagard Liquid [package insert], Westlake Village, CA; Baxter: July 2011.
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. Available at: http://www.cpgn.net/web/uploadfile/2011/0125/20110125015723259.pdf
Cortese I, Chaudhry V, So YT, et al. Evidence-based guideline update: Plasmapheresis in neurologic disorders: report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology. Neurology. 2011 Jan 18;76(3):294-300. Available at: http://www.aan.com/globals/axon/assets/8131.pdf
Barth D, Nabavi Nouri M, Ng E, Nwe P, Bril V. Comparison of IVIg and PLEX in patients with myasthenia gravis. Neurology. 2011 Jun 7;76(23):2017-23.
Gilhus NE, Owe JF, Hoff JM, et al. Myasthenia gravis: a review of available treatment approaches. Autoimmune Dis. 2011;2011:847393.
Keogh M, Sedehizadeh S, Maddison P. Treatment for Lambert-Eaton myasthenic syndrome. Cochrane Database Syst Rev. 2011 Feb 16;(2):CD003279
Kim JY, Park KD, Richman DP. Treatment of myasthenia gravis based on its immunopathogenesis. J Clin Neurol. 2011 Dec;7(4):173-83.
Sanadze AG. Efficacy and practicability of using intravenous human immunoglobulin in the pathogenetic treatment of patients with generalized myasthenia. Zh Nevrol Psikhiatr Im S S Korsakova. 2011;111(6):29-32. Russian.
Bird SJ. Treatment of myasthenia gravis. UpToDate. June 2013.
Bivigam [Prescribing Information], Boca Raton, FL : Biotest Pharmaceuticals Corp.; April 2014.
Flebogamma [Prescribing Information],Barcelona, Spain; Institutio Grifols, S.A.; August 2014.
Gammaked [Prescribing Information], Research Triangle Park, NC; Grifolis Therapeutics Inc.; September 2013.
Octagam 5% [Prescribing Information], Hoboken, NJ: Octapharma USA; October 2013.
Octagam 10% [Prescribing Information], Hoboken, NJ: Octapharma USA; August 2014.
HyQvia [Prescribing Information]. Westlake Village, CA; Baxter: September 2014.