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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-J2000-78

Original Effective Date: 06/15/17

Reviewed: 05/10/17

Revised: 00/00/00

Subject: Ocrelizumab (Ocrevus®) Infusion

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.

           
Dosage/ Administration Position Statement 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 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. 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. An initial attack may present as a clinically isolated syndrome (CIS); individuals presenting with this syndrome are high risk for subsequent conversion to clinically definite MS (CDMS).

Disease-modifying therapy is focused on slowing the progression of the disease and reducing the frequency of relapses. Treatment options include dimethyl fumarate (Tecfidera), fingolimod (Gilenya), teriflunomide (Aubagio), glatiramer acetate (Copaxone, Glatopa), interferon beta-1a (Avonex, Rebif), interferon beta-1b (Betaseron, Extavia), peg-interferon beta-1a (Plegridy), natalizumab (Tysabri), mitoxantrone (Novantrone), alemtuzumab (Lemtrada), and daclizumab (Zinbryta). The MS Coalition recommends initiation of treatment with an FDA-approved disease-modifying treatment as soon as possible following diagnosis of relapsing disease, for individuals with a first clinical event and MRI features consistent with MS, and for individuals with progressive MS who continue to have clinical relapse or inflammatory activity.

The Food and Drug Administration (FDA) approved ocrelizumab (Ocrevus®) in April 2017 for the treatment of relapsing or primary progressive forms of MS. Ocrelizumab is a humanized monoclonal antibody that is directed against CD20-expressing B-cells. The exact mechanism is unknown but it is expected to interfere with antibody-dependent and complement-mediated cytotoxicity.

Ocrelizumab was evaluated in patients with relapsing MS in two identical randomized, double-blind, active-controlled phase 3 trials. Ocrelizumab 600 mg intravenous infusion every 24 weeks was compared to interferon beta-1a (Rebif) 44 mcg three times weekly subcutaneous injection. The primary endpoint was the Annualized Relapse Rate (ARR) at 96 weeks. There was a significant reduction in the ARR in both trials with ocrelizumab as compared to interferon beta-1a (0.16 vs 0.29, p<0.001) . Additionally, ocrelizumab demonstrated a significant reduction in the percentage of patients with disability progression confirmed at 12 weeks (9.1% vs 13.6%, p<0.001) and 24 weeks (6.9% vs 10.5%, p=0.003). The mean number of T1 gadolinium-enhancing lesions and T2 hyperintense lesions on MRI were lower in the ocrelizumab treatment groups as compared to interferon-beta-1a. The most common adverse reactions with ocrelizumab were infusion reaction (34.3%), nasopharyngitis, upper respiratory tract infection, headache, and urinary tract infection. Neoplasms occurred more commonly with ocrelizumab as compared to interferon beta-1a (0.5% vs 0.2%).

Ocrelizumab was evaluated in 732 patients with primary progressive multiple sclerosis in a phase 3, randomized, double-blind, placebo-controlled trial for at least 120 weeks and until a prespecified number of confirmed disability progression events occurred. The percentage of patients with disability progression confirmed at 12 weeks was the primary end point. Ocrelizumab had fewer patients with 12-week confirmed disability progression as compared to placebo (32.9% vs 39.3%, p=0.03). Secondary endpoints of 24-week confirmed disability progression, ambulation speed, total volume of brain lesions on T2-weighted lesions, and change in brain volume were all significantly improved with ocrelizumab as compared to placebo. There was no difference in the 36 item Short-form Health Survey (SF-36) between groups. Infusion reactions and upper respiratory infection occurred more commonly with ocrelizumab. Neoplasms also occurred more frequently with ocrelizumab as compared to placebo (2.3% vs 0.8%).

POSITION STATEMENT:

I. Initiation of ocrelizumab (Ocrevus) meets the definition of medical necessity when ALL of the following are met:

1. Multiple Sclerosis (MS)

a. Member is diagnosed with ONE of the following:

i. Relapsing form of multiple sclerosis (MS) (i.e. relapsing-remitting MS [RRMS], secondary-progressive MS [SPMS] with relapsing disease, progressive-relapsing MS [PRMS])

ii. Primary Progressive MS

b. Member has been screened for hepatitis B virus and does not have an active hepatitis B virus infection

c. Ocrelizumab will NOT be used in combination with ANY of the following:

i. Alemtuzumab (Lemtrada)

ii. Daclizumab (Zinbryta)

iii. Dimethyl fumarate (Tecfidera)

iv. Fingolimod (Gilenya)

v. Glatiramer acetate (Copaxone, Glatopa)

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

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

viii. Mitoxantrone (Novantrone)

ix. Natalizumab (Tysabri)

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

xi. Teriflunomide (Aubagio)

d. The dose does not exceed 600 mg every 6 months*

*The first dose is given as a 300 mg infusion on day 1 and 15

Approval duration: 1 year

II. Continuation of ocrelizumab (Ocrevus) meets the definition of medical necessity for multiple sclerosis when ALL of the following are met:

1. Ocrelizumab will NOT be used in combination with ANY of the following:

a. Alemtuzumab (Lemtrada)

b. Daclizumab (Zinbryta)

c. Dimethyl fumarate (Tecfidera)

d. Fingolimod (Gilenya)

e. Glatiramer acetate (Copaxone, Glatopa)

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

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

h. Mitoxantrone (Novantrone)

i. Natalizumab (Tysabri)

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

k. Teriflunomide (Aubagio)

2. Member has demonstrated a beneficial response to therapy

3. Authorization/reauthorization for ocrelizumab 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

4. The dose does not exceed 600 mg every 6 months

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

Administration should be provided by a healthcare professional with access to appropriate medical support to manage severe reactions such as serious infusion reactions. Pre-medicate with methylprednisolone (or an equivalent corticosteroid) and an antihistamine (e.g., diphenhydramine) prior to each infusion. Hepatitis B virus screening is required before the first dose.

• Initial dose: 300 mg intravenous infusion, followed two weeks later by a second 300 mg intravenous infusion.

• Subsequent doses: single 600 mg intravenous infusion every 6 months.

• Observe the patient for at least one hour after the completion of the infusion

Dose Adjustments

Dose modifications in response to infusion reactions depends on the severity.

Life-threatening Infusion Reactions: Immediately stop and permanently discontinue if there are signs of a life-threatening or disabling infusion reaction.

Severe Infusion Reactions: Immediately interrupt the infusion and administer appropriate supportive treatment, as necessary. Restart the infusion only after all symptoms have resolved. See prescribing information for restarting dose.

Mild to Moderate Infusion Reactions: Reduce the infusion rate to half the rate at the onset of the infusion reaction and maintain the reduced rate for at least 30 minutes. See prescribing information for dose increase.

Drug Availability

• 300 mg/10 mL in a single dose vial

PRECAUTIONS:

Contraindications

• Active hepatitis B virus infection

• History of life-threatening infusion reaction to ocrelizumab

Precautions/Warnings

• Infusion reactions: Management recommendations for infusion reactions depend on the type and severity of the reaction. Permanently discontinue if a life-threatening or disabling infusion reaction occurs

• Infections: Delay administration in patients with an active infection until the infection is resolved. Vaccination with live-attenuated or live vaccines is not recommended during treatment with and after discontinuation, until B-cell repletion

• Malignancies: An increased risk of malignancy, including breast cancer may exist

BILLING/CODING INFORMATION:

The following codes may be used to describe:

HCPCS Coding

C9399

Unclassified drugs or biologicals

J3590

Unclassified biologics

ICD-10 Diagnoses 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 Part D: BCBSF has delegated to Prime Therapeutics authority to make coverage determinations for the Medicare Part D services referenced in this guideline.

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

DEFINITIONS:

Progressive multifocal leukoencephalopathy (PML): an opportunistic viral infection of the brain that usually leads to death or severe disability.

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

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

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

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

RELATED GUIDELINES:

Dimethyl Fumarate (Tecfidera), 09-J1000-96
Fingolimod (Gilenya™), 09-J1000-30

Magnetic Resonance Imaging (MRI) Brain and Head, 04-70540-11

Multiple Sclerosis Self Injectable Therapy, 09-J1000-39

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

Teriflunomide (Aubagio), 09-J1000-82

OTHER:

None

REFERENCES:

  1. Clinical Pharmacology [Internet]. Tampa (FL): Gold Standard, Inc.; 2017 [cited 2017-04-24]. Available from: http://www.clinicalpharmacology.com/.
  2. DRUGDEX® System [Internet]. Greenwood Village (CO): Thomson Micromedex; Updated periodically [cited 2017-04-24]. Available from: http://www.thomsonhc.com/.
  3. Hauser SL, Bar-Or A, Comi G et al. Ocrelizumab versus interferon beta-1a in relapsing multiple sclerosis. N Engl J Med 2017; 376: 221-34.
  4. Montalban X, Hauser SL, Kappos L et al. Ocrelizumab versus placebo in primary progressive multiple sclerosis. N Engl J Med 2017; 376:209-20.
  5. 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 04/26/2016.
  6. Ocrevus [prescribing information]. Genentech, Inc. South San Francisco, CA. March 2017.

COMMITTEE APPROVAL:

This Medical Coverage Guideline (MCG) was approved by the BCBSF Pharmacy Policy Committee on 05/10/17.

GUIDELINE UPDATE INFORMATION:

06/15/17

New Medical Coverage Guideline.

Date Printed: August 18, 2017: 10:28 AM