Effective Date:

a)    This policy will apply to all services performed on or after the above revision date which will become the new effective date.

b)    For all services referred to in this policy that were performed before the revision date, contact customer service for the rules that would apply.

The treatment of multiple sclerosis has become more complex and more successful over the past two decades. Some treatments require pre-authorization, such as Ampyra and Lemtrada.

  I.Intravenous Steroid Treatment

Intravenous steroid therapy is medically necessary for either of the following indications:

             A.  Treatment of acute exacerbations of multiple sclerosis when the acute relapse is characterized by functionally disabling symptoms with documented evidence of neurological impairment (persons who have previously responded in a relapse phase are more likely to do so in the future).

              B.  Use of intermittent pulse dose corticosteroids as a maintenance treatment for multiple sclerosis to delay disease progression.

In most cases, members can be treated in the outpatient setting. Hospital admission for intravenous steroid therapy may be medically necessary for the treatment of an acute exacerbation of multiple sclerosis that results in any of the following severe neurological deficits:

              1)  Acute fulminant multiple sclerosis characterized by headache, vomiting, convulsions and eventually coma, with severe compromise of functioning of the central nervous system; or

              2)  Acute quadriplegia; or

              3)  Acute pseudobulbar palsy; or

              4)  Acute transverse myelitis (or Brown-Sequard syndrome) with loss of function below the level of a suspected lesion in the spinal cord; or

              5)  Acute cerebral symptoms with severe loss of intellectual capacity; or

              6)  Acute epileptic seizure(s); or

              7)  Acute visual loss.

An inpatient stay may also be considered medically necessary for persons who have had previous complications from high dose intravenous steroids that justify an inpatient admission.

II.      Other Treatments

              A.  Clinically Isolated Syndrome (CIS) Suggestive of Multiple Sclerosis. Copaxone (glatiramer acetate injection) is considered medically necessary for treatment of persons who have experienced a first clinical episode and have magnetic resonance imaging (MRI) features consistent with multiple sclerosis.

             B.  Relapsing, Remitting Multiple Sclerosis. The following treatments are considered medically necessary for treatment of relapsing, remitting multiple sclerosis (but not for treatment of chronic progressive multiple sclerosis):

Preferred Products:

·   Avonex, Betaseron, Copaxone, glatiramer, dimethyl fumarate, Kesimpta, fingolimod

Non-Preferred Products:

·   Gilenya, and Aubagio

·   Lemtrada, Mavenclad, and Rituxan (rituximab) – Covered only after trial and failure of at least 2 preferred products

·   Ocrevus (ocrelizumab) – Covered only after trial and failure of at least 2 preferred products

             C.  Chronic Progressive Multiple Sclerosis. Novantrone (Mitoxantrone)* is considered medically necessary for clinically deteriorating persons with either relapsing remitting or chronic progressive forms of multiple sclerosis.

             D.  Primary Progressive Multiple Sclerosis. Rituxan (rituximab) is considered medically necessary for primary progressive multiple sclerosis. Ocrevus (ocrelizumab) is considered medically necessary for members age 18-55 meeting the following criteria:

                          1)  Trial/failure with (Rituxan) rituximab; OR

                          2)  The most recent Expanded Disability Status Scale (EDSS) score is 3.0 – 6.5 at initial request, AND

                          3)  Disease duration from onset of MS symptoms <15 years with an EDSS score of >5.0 at most recent screening OR disease duration from onset of MS symptoms <10 years with an EDSS score of <5.0 at most recent screening, AND

                          4)  A score on the pyramidal functions component of the Functional Systems Scale of at least 2 (range, 0 – 6, with higher scores indicating greater disability) AND

                          5)  A documented history or the presence at screening of an elevated IgG index or at least one IgG oligoclonal band detected in the cerebrospinal fluid.

              E.  Plasma exchange/plasmapheresis is considered medically necessary for individuals with acute, severe neurological deficits caused by multiple sclerosis that have a poor response to treatment with high-dose glucocorticoids.

              F.  Secondary Progressive Multiple Sclerosis (SPMS) – Mavenclad is considered medically necessary for secondary progressive multiple sclerosis.

* Because of the potential for functional cardiac changes, the product labeling for Novantrone states that persons receiving Novantrone should have their left ventricular ejection fraction (LVEF) evaluated by echocardiogram or MUGA prior to every dose.

Codes Used In This BI:

1.     Experimental and Investigational Interventions:

The following interventions are considered experimental and investigational for multiple sclerosis:

• Alpha-interferon
• Anti-T-cell monoclonal antibodies other than Natalizumab (Tysabri, Antegren)
• Anti-lymphocyte globulin
• Cooling garment
• Cyclophosphamide (Cytoxan)
• Cyclosporine (Sandimmune)
• Dietary interventions (e.g., gluten-free diets, low fat diets, linoleate supplementation to diet, and dietary regimens with polyunsaturated fatty acids)
• Electronystagmography (in the absence of vertigo or balance disorder)
• Erythropoiesis stimulating agents
• Gamma-interferon
• Hyperbaric oxygen
• IL-2-toxin
• Methotrexate
• Naltrexone
• Oral myelin (Myloral)
• Otoacoustic emissions (in the absence of signs of hearing loss)
• Photopheresis
• Procarin (transdermal histamine)
• Pulsed magnetic field therapy
• PUVA (psoralen ultraviolet light)
• Stem cell transplantation
• Statins
• T-cell receptor therapy
• T-cell vaccination
• Total lymphoid irradiation
• Transforming growth factor (TGF)-beta
• Tumor necrosis factor antagonists
• Tympanometry (in the absence of hearing loss). 
1. Neutralizing Antibodies against Interferon Beta Assays of neutralizing antibodies (NABs) against interferon beta (Betaseron) are considered to be experimental and investigational.

3.     APOE Genotyping-APOE genotyping of individuals with multiple sclerosis is considered experimental/investigative.  Brainstem Auditory Evoked Response-Brainstem Auditory Evoked Response is considered experimental and investigational in diagnosing multiple sclerosis

4.     Transcranial Brain Sonography-Transcranial brain sonography is considered experimental and investigational in predicting disease progression in MS.

1.    National Institute for Health and Clinical Excellence (NICE) Tysabri monograph at: http://www.emea.europa.eu/humandocs/PDFs/EPAR/tysabri/emea-combined-h603en.pdf

2.    Galetta S L, Markowitz C, Lee AG. Immunomodulatory agents for the treatment of relapsing multiple sclerosis: A systematic review. Archiv Internl Med. 2002; 162(19):2161-2169.

3.    La Mantia L, Milanese C, D"Amico R. Meta-analysis of clinical trials with copolymer 1 in multiple sclerosis. Europ Neurol. 2000; 43(4):189-193.

4.    Miller DM, Weinstock-Guttman B, Bethoux F, et al. A meta-analysis of methylprednisolone in recovery from multiple sclerosis exacerbations. Multip Scleros. 2000; 6(4):267-273.

5.    Shehata N, Kouroukis C, Kelton JG. A review of randomized controlled trials using therapeutic apheresis. Transfus Med Rev. 2002; 16(3):200-229.

6.    Brusaferri F, Candelise L. Steroids for multiple sclerosis and optic neuritis: A meta-analysis of randomized controlled clinical trials. J Neurol. 2000; 247(6):435-442.

7.    Blue Cross Blue Shield Association (BCBSA), Technology Evaluation Center (TEC). Extracorporeal Photopheresis for the treatment of autoimmune disease. TEC Assessment Program. Chicago IL: BCBSA; 2001:27

8.    Taus C, Giuliani G, Pucci E, et al. Amantadine for fatigue in multiple sclerosis. Cochrane Database Syst Rev. 2003; (2):CD002818.

9.    Solari A, Uitdehaag B, Giuliani G, et al. Amino pyridines for symptomatic treatment in multiple sclerosis. Cochrane Database Syst Rev. 2002; (4):CD001330.

10.   Shakespeare DT, Boggild M, Young C. Anti-spasticity agents for multiple sclerosis. Cochrane Database Syst Rev. 2003; (4):CD001332.

11.   Nicholas RS, Friede T, Hollis S, Young CA. Anticholinergics for urinary symptoms in multiple sclerosis (Protocol for Cochrane Review). Cochrane Database Syst Rev. 2003; (2):CD004193.

12.   Casetta I, Iuliano G. Azathioprine treatment for multiple sclerosis (Protocol for Cochrane Review). Cochrane Database Syst Rev. 2003; (1):CD003982.

13.   Killestein J, Polman CH, Uitdehaag BMJ. Cannabinoids for multiple sclerosis (Protocol for Cochrane Review). Cochrane Database Syst Rev. 2002; (4):CD003981.

14.   Filippini G, Brusaferri F, Sibley WA, et al. Corticosteroids or ACTH for acute exacerbations in multiple sclerosis. Cochrane Database Syst Rev. 2000; (4):CD001331.

15.   La Mantia L, Milanese C, Mascoli N, et al. Cyclophosphamide for multiple sclerosis. Cochrane Database Syst Rev. 2002; (3):CD002819.

16.   Farinotti M, Simi S, Lupo D, et al. Dietary interventions for multiple sclerosis (Protocol for Cochrane Review). Cochrane Database Syst Rev. 2003; (2):CD004192.

17.   Bennett M, Heard R. Hyperbaric oxygen therapy for multiple sclerosis. Cochrane Database Syst Rev. 2004; (1):CD003057.

18.   Rice GPA, Ebers G, Fredrikson S, et al. Interferon beta for secondary progressive multiple sclerosis (Protocol for Cochrane Review). Cochrane Database Syst Rev. 2005; (1):CD005181.

19.   Rice GPA, Incorvaia B, Munari L, et al. Interferon in relapsing-remitting multiple sclerosis. Cochrane Database Syst Rev. 2001; (4):CD002002.

20.   Gray OM, McDonnell GV, Forbes RB. Intravenous immunoglobulins for multiple sclerosis. Cochrane Database Syst Rev. 2003; (3):CD002936.

21.   Gray O, McDonnell GV, Forbes RB. Methotrexate for multiple sclerosis. Cochrane Database Syst Rev. 2004; (2):CD003208.

22.   Filippi M, Martinelli-Boneschi F, Comi G, Rovaris M. Mitoxantrone for secondary progressive and progressive relapsing multiple sclerosis (Protocol for Cochrane Review). Cochrane Database Syst Rev. 2000; (2):CD002127.

23.   Ciucci G, Floriani I. Plasma exchange for multiple sclerosis (Protocol for Cochrane Review). Cochrane Database Syst Rev. 2001 ;( 3):CD003609.

24.   Munari L, Lovati R, Boiko A. Therapy with glatiramer acetate for multiple sclerosis. Cochrane Database Syst Rev. 2003; (4):CD004678.

25.   Mills RJ, Friede T, Young CA. Treatment for ataxia in multiple sclerosis (Protocol for Cochrane Review). Cochrane Database Syst Rev. 2004; (4):CD005029.

26.   Rog DJ, Young C, Hollis S, Friede T. Treatment of neuropathic pain for multiple sclerosis (Protocol for Cochrane Review). Cochrane Database Syst Rev. 2001; (4):CD003736.

27.   U.S. Department of Health and Human Services, Food, and Drug Administration (FDA). Tysabri (Natalizumab) information. Rockville, MD: FDA; November 26, 2004.

28.   O`Connor PW, Goodman A, Willmer-Hulme AJ, et al. Randomized multicenter trial of Natalizumab in acute MS relapses: Clinical and MRI effects. Neurology. 2004; 62(11):2038-2043.

29.   Miller DH, Khan OA, Sheremata WA, et al. A controlled trial of Natalizumab for relapsing multiple sclerosis. N Engl J Med. 2003; 348(1):15-23.

30.   Gilenya Product Information.  Novartis.  September 2010

31.   Chun J, Hartung HP.  Mechanism of action of oral fingolimod (TRY720 in multiple sclerosis.  Clin Neuropharmacol.  2010; 33(2):91-101.

32.   Aubagio prescribing information. Genzyme Corporation. September 2012

33.   Tecfidera prescribing information. Biogen Idec Inc. March 2013.

34.   Plegridy prescribing information. Biogen Idec Inc. August 2014.

35.   Lemtrada prescribing information.  Genzyme Corporation.  Cambridge, MA. November 2014.

36.   Montalban X, Hauser SL, Kapos L, et al; ORATORIO Clinical Investigators. Ocrelizumab versus placebo in primary progressive multiple sclerosis. N Engl J Med. 2017;376(3):209-220.

37.   Mavenclad Package Insert. Rockland, MD; EMD Serono,Inc.; March 2019.

Addendum:

1.    Effective 01/01/2017: Coverage: Updated preferred and non-preferred products for relapsing/remitting MS. Added Zinbryta to policy.

CPT/HCPCS Code Updates: Removed HCPCS codes J1565 & J1567 from the BI. These codes are no longer valid.

2.    Effective 5/1/2017: Updated non-preferred product Gilenya criteria

3.    Effective 9/1/2017: Updated policy to reflect rituximab and Ocrevus coverage criteria.

4.    Effective 10/1/2017: Added new HCPCS code (C9494) to policy.

5.    Effective 1/1/2018: 2018 Code Updates: HCPCS code C9494 was deleted & replaced with new HCPCS code J2350.

Coverage: Removed Rebif and Plegridy as covered products.

6.    Effective 1/1/2019: Coverage: Updated criteria for coverage of Ocrevus in RRMS and PPMS. Removed PA requirement for Aubagio and Gilenya.

2019 Code Updates: Deleted HCPCS code J9310 & replaced with new HCPCS code J9312.

7.    Effective 04/01/2019: Updated coverage criteria for Ocrevus in RRMS to require t/f of at least two preferred products.

8.    Effective 01/01/2020: Updated coverage criteria to include Mavenclad for SPMS.

9.    Effective 04/01/2020: Updated coverage for Ocrevus for PPMS.

10. Effective 01/01/2021: Updated coverage to include Kesimpta as non-preferred product.

11. Effective 06/01/2023: Updated preferred products.