Subject: Multiple Sclerosis

Status	Drug	PR	PR-QL	PR-AL	ST	M EX‡
P	Avonex®  (interferon beta-1a)
P	Copaxone®  (glatiramer)
P	Rebif®  (interferon beta-1a)
NP	Gilenya™  (fingolimod)	X	X
FE	Ampyra®  (dalfampridine)	X				X
FE	Betaseron®  (interferon beta-1b)				X	X
FE	Extavia®  (interferon beta-1b)				X	X
FE	Tysabri®  (natalizumab)	X				X

Policy:

1. Precertification Criteria

Under some plans, including plans that use an open or closed formulary, Ampyra, Gilenya and Tysabri are subject to precertification.  If precertification requirements apply Aetna considers Ampyra, Gilenya and Tysabri to be medically necessary for those members who meet the following precertification criteria:

For Ampyra – A

A.  A documented diagnosis of multiple sclerosis
      AND
     Continued impairment in walking

For Gilenya – B and E

B.  A documented diagnosis of relapsing forms of multiple sclerosis AND discontinuation of other therapies used for treating multiple sclerosis (e.g. Avonex,  Copaxone, Rebif, Betaseron, Extavia, Tysabri) AND

• A documented recent (within 6 months) complete blood count (CBC) AND
• A documented recent (within 6 months) liver transaminase and bilirubin AND
• A documented recent (within 6 months) EKG if member is using a antiarrhythmic (such as beta-blockers, calcium channel blockers, Class Ia and Class III antiarrhythmics) or with history of 2nd degree or higher AV block, sick sinus syndrome, prolonged QT interval, ischemic cardiac disease, congestive heart failure, heart rate below 55 bpm, or irregular heart beat AND
• A documented baseline ophthalmologic examination AND
• A documented history of chicken pox or administration of the varicella zoster vaccine (VZV).  If history of chicken pox or administration of VZV is unknown then titers should be drawn and if low VZV should be considered. AND
• If female, a documented negative pregnancy test

For Tysabri  - C OR D

C. A documented diagnosis of multiple sclerosis

AND

One of the following:

• Contraindication to one preferred alternative – Avonex, Copaxone or Rebif OR
• Intolerance to one preferred alternative – Avonex, Copaxone or Rebif OR 
• Allergy to one preferred alternative – Avonex, Copaxone or Rebif OR 
• Failure of an adequate trial of six months of one preferred alternative – Avonex, Copaxone or Rebif

OR

D. A documented diagnosis of Crohn’s disease
AND

One of the following:

• Contraindication to one preferred alternative – Cimzia, Humira or Remicade OR 
• Intolerance to one preferred alternative – Cimzia, Humira or Remicade OR 
• Allergy to one preferred alternative – Cimzia, Humira or Remicade OR 
• Failure of an adequate trial of one month of one preferred alternative – Cimzia, Humira or Remicade

 

E.  Quantity Limits:  According to the manufacturer, Gilenya can be dosed to a maximum daily dose at the interval as indicated in the table below.  A quantity of Gilenya will be considered medically necessary as indicated in the table below:

Drug	Maximum Daily Dose/ Dosing Interval	Dosage Strength	Quantity Limits
Gilenya	0.5mg/once daily	0.5mg	Up to 30 capsules in 30 days





For coverage of additional quantities, member's treating physician must request prior authorization through the Aetna Pharmacy Management Precertification Unit. Additional quantities of the above medications will be considered medically necessary for those members who meet the following criterion:

• Member's physician provides documentation (controlled clinical trial) from the peer-reviewed medical literature for use of a higher dose
  



2. Step Therapy Criteria

Under some plans, including plans that use an open or closed formulary, Betaseron and Extavia is subject to step-therapy.  Aetna considers Betaseron and Extavia to be medically necessary for those members who meet the following step-therapy criterion:

A documented trial of six months of one of the following agents – Avonex, Copaxone or Rebif – alternatives on the Preferred Drug List.

If it is medically necessary for a member to be treated initially with a medication subject to step-therapy, the member, a person appointed to manage the member’s care, or the member's treating physician may contact the Aetna Pharmacy Management Precertification Unit to request coverage as a medical exception at 1-800-414-2386. (See criteria under section III below).

 


3. Medical Exception Criteria

Ampyra and Tysabri are currently listed on the Aetna Formulary Exclusions List.* Therefore, Ampyra and Tysabri are excluded from coverage for members enrolled in prescription drug benefits plans that use a closed formulary, unless a medical exception is granted.  Aetna considers Ampyra and Tysabri to be medically necessary for those members who meet any of the following criteria:

Betaseron and Extavia are currently listed on the Aetna Formulary Exclusions and Step-Therapy lists.* Therefore, Betaseron and Extavia are excluded from coverage for members enrolled in prescription drug benefit plans that use a closed formulary or that require step-therapy criteria, unless a medical exception is granted.  Aetna considers Betaseron and Extavia to be medically necessary for those members who meet the criteria specified below:

For Betaseron and Extavia

A documented:

• Contraindication to one of the following preferred agents – Avonex, Copaxone or Rebif OR
• Intolerance to one of the following preferred agents – Avonex, Copaxone or Rebif OR 
• Allergy to one of the following preferred agents – Avonex, Copaxone or Rebif OR 
• Failure of an adequate trial of six months one of the following preferred agents – Avonex, Copaxone or Rebif

For Ampyra – A

A. A documented diagnosis of multiple sclerosis AND continued impairment in walking.

For Tysabri – B OR C

B. A documented diagnosis of multiple sclerosis
AND

One of the following:

• Contraindication to one preferred alternative – Avonex, Copaxone or Rebif OR 
• Intolerance to one preferred alternative – Avonex, Copaxone or Rebif OR 
• Allergy to one preferred alternative – Avonex, Copaxone or Rebif OR 
• Failure of an adequate trial of six months of one preferred alternative – Avonex, Copaxone or Rebif
  OR 

C. A documented diagnosis of Crohn’s disease
AND

One of the following:

• Contraindication to one preferred alternative – Cimzia, Humira or Remicade OR 
• Intolerance to one preferred alternative – Cimzia, Humira or Remicade OR 
• Allergy to one preferred alternative – Cimzia, Humira or Remicade OR 
• Failure of an adequate trial of one month of one preferred alternative – Cimzia, Humira or Remicade

Place of Service:

Outpatient

The above policy is based on the following references:

 

1. DrugPoints® System ( www.statref.com) Thomson Micromedex, Greenwood Village, CO. Updated periodically.
2. AHFS Drug Information® with AHFSfirstReleases®. ( www.statref.com), American Society Of Health-System Pharmacists®, Bethesda, MD. Updated periodically.
3. DRUGDEX® System [Internet database]. Greenwood Village, Colo: Thomson Micromedex. Updated periodically.
4. Drug Facts and Comparisons on-line. (www.drugfacts.com), Wolters Kluwer Health, St. Louis, MO. Updated periodically.
5. PDR® Electronic Library™ [Internet database]. Greenwood Village, Colo: Thomson Micromedex. Updated periodically.
6. Courtney AM, Treadaway K, Remington G, Frohman E. Multiple Sclerosis. Med Clin N Am. 2009;93:451-76.
7. Compston A, Coles A. Multiple sclerosis.  Lancet. 2008;372:1502-17.
8. Goodman AD, Rossman H, Bar-Or A, et al. GLANCE. Results of a phase 2, randomized, double-blind, placebo-controlled study. Neurology. 2009;72:806-12.
9. Wolinsky JS, Narayana PA, O’Connor P, et al. Glatiramer acetate in primary progressive multiple sclerosis: Results of a multinational, multicenter, double-blind, placebo-controlled trial. Ann Neurol. 2007;61:14-24.
10. Mikol DD, Barkhof F, Chang P, et al on behalf of the REGARD study group. Comparison of subcutaneous interferon beta-1a with glatiramer acetate in patients with relapsing multiple sclerosis (the Rebif vs Glatiramer Acetate in Relapsing MS Disease [REGARD] study): a multicenter, randomized, parallel, open label trial. Lancet Neurol. 2008;7:903-14.
11. Goodin DS, Cohen BA, O’Connor P, et al. Assessment: The use of natalizumab (Tysabri) for the treatment of multiple sclerosis (an evidence-based review). Report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology. Neurology. 2008;71:766-73.
12. Fllippini G, Munari L, Incorvala B, et al. Interferons in relapsing remitting multiple sclerosis: a systematic review. Lancet. 2003; 361:545-52.
13. Durelli L, Verdun E, Barbero P, et al and the Independent Comparison of Interferon (INCOMIN) Trial Study Group. Every-other-day interferon beta-1b versus once-weekly interferon beta-1a for multiple sclerosis: results of a 2 year prospective randomized multicenter study (INCOMIN). Lancet 2002;359:1453-60.
14. Goodin DS, Frohman EM, Garmany Jr GP, et al. Disease modifying therapies in multiple sclerosis. Report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology and the MS Council for Clinical Practice Guidelines. Neurology. 2002;58:169-78.
15. Rojas JI, Romano M, Ciapponi A, Patrucco L, Cristiano E. Interferon beta for primary progressive multiple sclerosis. Cochrane Database Syst Rev. 2009;(1):CD006643.
16. Clerico M, Faggiano F, Palace J, et al. Recombinant interferon beta or glatiramer acetate for delaying conversion of the first demyelinating event to multiple sclerosis. Cochrane Databasde Syst Rev. 2008;(2):CD005278.
17. Birnbaum G, Cree B, Altafullah I, et al. Combining beta interferon and atorvastatin may increase disease activity in multiple sclerosis. Neurology. 2008;71:1390-5.
18. Kappos L, Bates D, Hartung HP, et al. Natalizumab treatment for multiple sclerosis: recommendations for patient selection and monitoring. Lancet Neurol 2007;6:431-41.
19. Rudick RA, Stuart WH, Calabresi PA et al. A randomized placebo-controlled trial of natalizumab plus interferon beta-1a for relapsing multiple sclerosis. N Engl J Med 2006;354:911-23.
20. Beta interferon and glatiramer acetate for the treatment of multiple sclerosis. NICE Technology Appraisal Guidance #32, January 2002.
21. Coyle PK. Evidence-based medicine and clinical trials. Neurology. 2007;68(Suppl 4):S3-S7.
22. Ryan M, Deno S, and Zwibel HL. Review of the clinical debate regarding interventions for multiple sclerosis. J Manag Care Pharm. 2009;15(1) (Suppl S-b):S1-S17.
23. Panitch H, Goodin DS, Francis G, et al. Randomized, comparative study of interferon beta-1a treatment regimens in MS: The EVIDENCE Trial. Neurology. 2002;59:1496-506.
24. Koch-Henrikesen N, Sorensen PS, Christensen T, et al. A randomized study of two interferon-beta treatments in relapsing-remitting multiple sclerosis. Neurology. 2006;66:1056-1060.
25. Wiendl H, Hohlfeld R. Multiple sclerosis therapeutics. Unexpected outcomes clouding undisputed successes. Neurology. 2009;72:1008-15.
26. Hartung HP, Gonsette R, Konig N, et al. Mitoxantrone in progressive multiple sclerosis: a placebo-controlled, double-blind, randomized, multicentre trial. Lancet 2002;360:2018-25.
27. Polman CH, O’Connor PW, Havrdova E, et al. A randomized, placebo-controlled trial of natalizumab for relapsing multiple sclerosis. N Engl J Med. 2006;354:899-910.
28. Multiple Sclerosis Therapy Consensus Group (MSTCG). Basic and escalating immunomodulatory treatments in multiple sclerosis: Current therapeutic recommendations. J Neurol. 2008;255:1449-63.

 

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.

October 29, 2010