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This medical policy (medical coverage guideline) is Copyright 2017, Blue Cross and Blue Shield of Florida (BCBSF). All Rights Reserved. You may not copy or use this document or disclose its contents without the express written permission of BCBSF. The medical codes referenced in this document may be proprietary and owned by others. BCBSF makes no claim of ownership of such codes. Our use of such codes in this document is for explanation and guidance and should not be construed as a license for their use by you. Before utilizing the codes, please be sure that to the extent required, you have secured any appropriate licenses for such use. Current Procedural Terminology (CPT) is copyright 2017 American Medical Association. All Rights Reserved. No fee schedules, basic units, relative values, or related listings are included in CPT. The AMA assumes no liability for the data contained herein. Applicable FARS/DFARS restrictions apply to government use. CPT® is a trademark of the American Medical Association. The use of specific product names is illustrative only. It is not intended to be a recommendation of one product over another, and is not intended to represent a complete listing of all products available.

09-J1000-96

Original Effective Date: 06/15/13

Reviewed: 09/13/17

Revised: 10/15/17

Subject: Dimethyl Fumarate (Tecfidera®) Capsule

THIS MEDICAL COVERAGE GUIDELINE IS NOT AN AUTHORIZATION, CERTIFICATION, EXPLANATION OF BENEFITS, OR A GUARANTEE OF PAYMENT, NOR DOES IT SUBSTITUTE FOR OR CONSTITUTE MEDICAL ADVICE. ALL MEDICAL DECISIONS ARE SOLELY THE RESPONSIBILITY OF THE PATIENT AND PHYSICIAN. BENEFITS ARE DETERMINED BY THE GROUP CONTRACT, MEMBER BENEFIT BOOKLET, AND/OR INDIVIDUAL SUBSCRIBER CERTIFICATE IN EFFECT AT THE TIME SERVICES WERE RENDERED. THIS MEDICAL COVERAGE GUIDELINE APPLIES TO ALL LINES OF BUSINESS UNLESS OTHERWISE NOTED IN THE PROGRAM EXCEPTIONS SECTION.

           
Position Statement Dosage/ Administration Billing/Coding Reimbursement Program Exceptions Definitions
           
Related Guidelines Other References Updates  
           

DESCRIPTION:

Multiple sclerosis (MS) is a chronic disease affecting the central nervous system (CNS). It is characterized by triad of inflammation, demyelination, and scarring of the central nervous system and manifests as pathological (immune-mediated CNS demyelination and axonal injury) and clinical (exacerbations, disability progression) dissemination in time and space. Although the clinical course of the disease is capricious, MS has been categorized into four types: relapsing-remitting (RRMS), secondary progressive (SPMS), primary progressive (PPMS), and progressive-relapsing (PRMS). The most common type is RRMS, which is characterized by acute attacks followed by periods of remission.

Although a cure for MS remains elusive, several treatment options slow the progression of the disease and reduce the frequency of relapses. Currently there are ten Food and Drug Administration (FDA)-approved disease-modifying therapies (DMT) for MS. Interferon-beta (IFN-beta) (i.e., Avonex®, Rebif®, Betaseron®, Extavia®) and glatiramer acetate (Copaxone®) are self-administered injectable therapies and are commonly referred to as first-line agents in clinical practice guidelines. Several oral options have been approved by the FDA, including fingolimod (Gilenya™), teriflunomide (Aubagio®), and dimethyl fumarate (Tecfidera®). Dimethyl fumarate was approved in March 2013 for the treatment of relapsing forms of MS. Dimethyl fumarate’s mechanism of action has not been fully elucidated; however, it is hypothesized that it inhibits immune cells and molecules and may have anti-oxidant properties that protect against damage to the brain and spinal cord.

Two phase III studies demonstrated the efficacy of dimethyl fumarate in persons with RRMS. In each study, when compared to placebo, dimethyl fumarate treatment was associated with a significant reduction in relapse rate. However, only one of the two trials demonstrated dimethyl fumarate’s ability to significantly reduce disability progression when compared to placebo. To date, no head-to-head studies have evaluated its efficacy when compared to other therapies. While several clinical practice guidelines exist for MS, they have not been updated since 2002; as such, the role of newer oral agents is not addressed.

POSITION STATEMENT:

Comparative Effectiveness

The Food and Drug Administration has deemed the drug(s) or biological product(s) in this coverage policy to be appropriate for self-administration or administration by a caregiver (i.e., not a healthcare professional). Therefore, coverage (i.e., administration) in a provider-administered setting such as an outpatient hospital, ambulatory surgical suite, physician office, or emergency facility is not considered medically necessary.

NOTE: Aubagio, Avonex, Betaseron, Copaxone, Gilenya, Glatopa, Plegridy, Rebif and Tecfidera are preferred products for treatment of relapsing forms of multiple sclerosis.

Initiation of dimethyl fumarate (Tecfidera) meets the definition of medical necessity when ALL of the following criteria are met:

1. Member is diagnosed with a relapsing form of multiple sclerosis (i.e., relapsing remitting multiple sclerosis [RRMS], secondary progressive MS [SPMS], progressive-relapsing MS [PRMS]).

2. Dimethyl fumarate is not used in combination with ANY of the following:

a. Alemtuzumab (Lemtrada)

b. Daclizumab (Zinbryta)

c. Fingolimod (Gilenya)

d. Glatiramer acetate (Copaxone, Glatopa)

e. Interferon beta-1a (Avonex, Rebif)

f. Interferon beta-1b (Betaseron, Extavia)

g. Mitoxantrone (Novantrone)

h. Natalizumab (Tysabri)

i. Ocrelizumab (Ocrevus)

j. Peg-interferon beta-1a (Plegridy)

k. Teriflunomide (Aubagio)

1. The dose does not exceed 480 mg daily

Approval duration: 1 year

Continuation of dimethyl fumarate therapy meets the definition of medical necessity when ALL of the following criteria are met:

1. Member has demonstrated a beneficial response to therapy for treatment of a relapsing form of multiple sclerosis (i.e., relapsing remitting multiple sclerosis [RRMS], secondary progressive MS [SPMS], progressive-relapsing MS [PRMS]).

2. Authorization/reauthorization for dimethyl fumarate has been previously approved by Florida Blue or another health plan in the past 2 years, OR the member currently meets all indication-specific initiation criteria

3. Dimethyl fumarate is not used in combination with ANY of the following:

a. Alemtuzumab (Lemtrada)

b. Daclizumab (Zinbryta)

c. Fingolimod (Gilenya)

d. Glatiramer acetate (Copaxone, Glatopa)

e. Interferon beta-1a (Avonex, Rebif)

f. Interferon beta-1b (Betaseron, Extavia)

g. Mitoxantrone (Novantrone)

h. Natalizumab (Tysabri)

i. Ocrelizumab (Ocrevus)

j. Peg-interferon beta-1a (Plegridy)

k. Teriflunomide (Aubagio)

1. The dose does not exceed 480 mg daily.

Approval duration: 1 year

DOSAGE/ADMINISTRATION:

THIS INFORMATION IS PROVIDED FOR INFORMATIONAL PURPOSES ONLY AND SHOULD NOT BE USED AS A SOURCE FOR MAKING PRESCRIBING OR OTHER MEDICAL DETERMINATIONS. PROVIDERS SHOULD REFER TO THE MANUFACTURER’S FULL PRESCRIBING INFORMATION FOR DOSAGE GUIDELINES AND OTHER INFORMATION RELATED TO THIS MEDICATION BEFORE MAKING ANY CLINICAL DECISIONS REGARDING ITS USAGE.

FDA-approved: dimethyl fumarate is indicated for the treatment of persons with relapsing forms of multiple sclerosis. The recommended initial dose is 120 mg twice daily for 7 days, followed by 240 mg twice daily thereafter. Dimethyl fumarate can be administered without regard to meals and the capsules should be swallowed whole and intact. Members should be instructed not to crush, chew, or sprinkle the capsule contents on food.

Dose Adjustments: information regarding dose adjustments was not published at the time of the review. In clinical trials, the dimethyl fumarate dose was adjusted or discontinued for elevations in liver transaminases (e.g., ALT/AST) or creatinine and for decreasing white blood cell count. The manufacturer has not provided specific instructions for dose adjustments in these situations.

Drug Availability: dimethyl fumarate is supplied as 120- and 240 mg delayed-release capsules.

PRECAUTIONS:

Anaphylaxis and angioedema: discontinue and do not restart therapy if this occurs.

Progressive multifocal leukoencephalopathy (PML): withhold at the first sign or symptom suggestive of PML.

Liver injury: Obtain serum aminotransferase, alkaline phosphatase, and total bilirubin levels before initiating and during treatment, as clinically indicated. Discontinue if clinically significant liver injury is suspected.

Lymphopenia: dimethyl fumarate may decrease lymphocyte counts; prior to therapy initiation, a recent complete blood count (i.e., within 6 months) should be available. Monitor CBC annually and as clinically indicated.

Flushing: in clinical trials, 40% of dimethyl fumarate treated subjects experienced flushing. Symptoms typically began soon after therapy initiation and usually improved over time. Administration of dimethyl fumarate with food may reduce the incidence of flushing.

Pregnancy and Lactation: dimethyl fumarate is classified as pregnancy category C. Although no adequate and well-controlled studies in pregnant women have been conducted, animal studies indicate that adverse effects on offspring survival, growth, sexual maturation and neurobehavioral function can occur when dimethyl fumarate is administered during pregnancy and lactation at clinically relevant doses.

BILLING/CODING INFORMATION:

The following codes may be used to describe:

HCPCS Coding:

J8499

Prescription drug, oral, non-chemotherapeutic, NOS

ICD-10 Diagnosis Codes That Support Medical Necessity:

G35

Multiple sclerosis

REIMBURSEMENT INFORMATION:

Refer to section entitled POSITION STATEMENT.

PROGRAM EXCEPTIONS:

Federal Employee Program (FEP): Follow FEP guidelines.

State Account Organization (SAO): Follow SAO guidelines.

Medicare Advantage Products: No National Coverage Determination (NCD) and/or Local Coverage Determination (LCD) were found at the time of the last guideline revised date.

Medicare Advantage: BCBSF has delegated to Prime Therapeutics authority to make coverage determinations for the Medicare Part D services referenced in this guideline.

DEFINITIONS:

Relapsing-remitting multiple sclerosis (RRMS): Characterized by acute attacks followed by periods of remission; primary form of MS that occurs in approximately 85% of individuals.

Primary-progressive multiple sclerosis (PPMS): Steadily progressive course from onset with no acute attacks; occurs in 10-15% of individuals with MS.

Secondary-progressive multiple sclerosis (SPMS): An initial period of RRMS, followed by a steadily progressive course, with or without acute relapses; 75-85% of individuals diagnosed with RRMS will transition to SPMS.

Progressive-relapsing multiple sclerosis (PRMS): Steadily progressive course from onset with acute attacks, with or without recovery; occurs in less than 5% of MS individuals.

RELATED GUIDELINES:

Botulinum Toxins, 09-J0000-29
Fingolimod (Gilenya™), 09-J1000-30

Immune Globulin Therapy, 09-J0000-06

Multiple Sclerosis Self Injectable Therapy, 09-J1000-39

Natalizumab (Tysabri®) IV, 09-J0000-73

Ocrelizumab (Ocrevus®), 09-J2000-78

Teriflunomide (Aubagio®) Tablets, 09-J1000-82

OTHER:

None applicable.

REFERENCES:

  1. AHFS Drug Information. Bethesda (MD): American Society of Health-System Pharmacists, Inc; 2016 [cited 2016-09-24].
  2. Bayer. Betaseron (interferon beta-1b) injection. 2014 [cited 2015-08-25]. In: DailyMed [Internet]. Bethesda (MD): National Library of Medicine. Available from: http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=66311f74-0472-4fa3-848a-06002ca0def5/.
  3. Biogen. Avonex (interferon beta-1a) injection. 2008 [cited 2015-08-25]. In: DailyMed [Internet]. Bethesda (MD): National Library of Medicine. Available from: http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=84d42ba4-6eef-41a7-a1d1-2cc887ef118d/.
  4. Biogen. Plegridy (peginterferon beta-1a) injection. 2014 [cited 2015-08-25]. In: DailyMed [Internet]. Bethesda (MD): National Library of Medicine. Available from: http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=08f0ea03-4e6d-195d-aef4-886e32befa95/.
  5. Biogen. Tecfidera (dimethyl fumarate) capsule. 2017 [cited 2017-08-30]. In: DailyMed [Internet]. Bethesda (MD): National Library of Medicine. Available from: http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=665d7e74-036c-5f68-5b67-ab84b9b49151/.
  6. Biogen. Tysabri (natalizumab) injection. 2015 [cited 2015-08-25]. In: DailyMed [Internet]. Bethesda (MD): National Library of Medicine. Available from: http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=c5fdde91-1989-4dd2-9129-4f3323ea2962/.
  7. Clinical Pharmacology [Internet]. Tampa (FL): Gold Standard, Inc.; 2017 [cited 2017-08-30]. Available from: http://www.clinicalpharmacology.com/.
  8. ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine; 2000 Feb 29 - [cited 2015-08-25]. Available from: http://clinicaltrials.gov/.
  9. DRUGDEX® System [Internet]. Greenwood Village (CO): Thomson Micromedex; Updated periodically [cited 2017-08-30]. Available from: http://www.thomsonhc.com/.
  10. EMD Serono. Rebif (interferon beta-1a) injection. 2015 [cited 2015-08-25]. In: DailyMed [Internet]. Bethesda (MD): National Library of Medicine. Available from: http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=c6fcb5d2-8fcd-44fa-a838-b84ee5f44f0f/.
  11. Fox RJ, Miller DH, Phillips JT, et al. Placebo-controlled phase 3 study of oral BG-12 or glatiramer in multiple sclerosis. N Engl J Med 2012;367(12):1087-97.
  12. Freedman MS. Treatment options for patients with multiple sclerosis who have suboptimal response to interferon-β therapy. Eur J Neurol 2014;21:377-87.
  13. Genzyme. Aubagio (teriflunomide) tablet, film coated. 2014 [cited 2015-08-25]. In: DailyMed [Internet]. Bethesda (MD): National Library of Medicine. Available from: http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=4650d12c-b9c8-4525-b07f-a2d773eca155/.
  14. Gold R, Kappos L, Arnold DL, et al. Placebo-controlled phase 3 study of oral BG-12 for relapsing multiple sclerosis. N Engl J Med 2012;367(12):1098-1107.
  15. Limmroth V. Treatment of relapsing-remitting multiple sclerosis: current and future algorithms. Eur J Neurol 2014;72:35-8.
  16. Mikol DD, Barkhof F, Chang P, et al. 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.
  17. Multiple Sclerosis Coalition. The use of disease-modifying therapies in multiple sclerosis: principles and current evidence. Available at http://www.nationalmssociety.org/getmedia/5ca284d3-fc7c-4ba5-b005-ab537d495c3c/DMT_Consensus_MS_Coalition_color. Accessed 09/26/2016.
  18. National Clinical Advisory Board of the National Multiple Sclerosis Society. Disease management consensus statement. Available at http://www.nationalmssociety.org/about-multiple-sclerosis/what-we-know-about-ms/treatments/index.aspx Accessed 08/13/2012.
  19. National Clinical Advisory Board of the National Multiple Sclerosis Society. Disease management consensus statement. Available at http://www.nationalmssociety.org/about-multiple-sclerosis/what-we-know-about-ms/treatments/index.aspx Accessed 08/13/2012.
  20. Novartis. Extavia (interferon beta-1b) injection. 2014 [cited 2015-08-25]. In: DailyMed [Internet]. Bethesda (MD): National Library of Medicine. Available from: http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=4cfdb571-ec4c-478f-bedc-e0669eeea504/.
  21. Novartis. Gilenya (fingolimod hydrochloride) capsule. 2015 [cited 2015-08-25]. In: DailyMed [Internet]. Bethesda (MD): National Library of Medicine. Available from: http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=cc9e1c8c-0e2b-44e2-878b-27057f786be9/.
  22. Oliver BJ, Kohli E, Kasper LH. Interferon therapy in relapsing-remitting multiple sclerosis: A systematic review and meta-analysis of the comparative trials. J Neurol Sci 2011;302:96-105.
  23. Orphan Drug Designations and Approval [Internet]. Silver Spring (MD): US Food and Drug Administration; 2016 [cited 2016-09-22]. Available from: http://www.accessdata.fda.gov/scripts/opdlisting/oopd/index.cfm/.
  24. Sandoz. Glatopa (glatiramer acetate) injection. 2015 [cited 2015-08-25]. In: DailyMed [Internet]. Bethesda (MD): National Library of Medicine. Available from: http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=5f01e40a-b6f6-40fb-b37c-3d06f1428e86/.
  25. Teva. Copaxone (glatiramer acetate) injection. 2014 [cited 2015-08-25]. In: DailyMed [Internet]. Bethesda (MD): National Library of Medicine. Available from: http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=aa88f583-4f5f-433b-80b4-1f4c9fb28357/.
  26. Wiendl H, Toyka KV, Rieckmann R, et.al. Basic and escalating immunomodulatory treatments in multiple sclerosis: current therapeutic recommendations. J Neurol 2008;255:1449-63.
  27. Wingerchuk DM, Carter JL. Multiple sclerosis: current and emerging disease-modifying therapies and treatment strategies. Mayo Clin Proc 2014;89:225-40.

COMMITTEE APPROVAL:

This Medical Coverage Guideline (MCG) was approved by the BCBSF Pharmacy Policy Committee on 09/13/17.

GUIDELINE UPDATE INFORMATION:

06/15/13

New Medical Coverage Guideline.

10/15/13

Revision to guideline; consisting of Change next review date so it will be reviewed the same time other drugs in its class are reviewed.

01/01/14

Revision to guideline; consisting of updating position statement.

10/15/14

Review and revision to guideline; consisting of reformatting position statement and updating references.

10/15/15

Review and revision to guideline; consisting of updating position statement and references.

11/01/15

Revision: ICD-9 Codes deleted.

01/01/17

Review and revision to guideline; consisting of updating position statement, precautions and references.

10/15/17

Review and revision to guideline; consisting of updating position statement and references.

Date Printed: October 23, 2017: 07:27 AM