Medical Policy

 

Subject: Ocrelizumab (Ocrevus™)
Document #: DRUG.00095 Publish Date:    12/27/2017
Status: Revised Last Review Date:    08/03/2017

Description/Scope

This document addresses the uses of ocrelizumab (Ocrevus™ Genentech, Inc, San Francisco, CA). Ocrelizumab is an immune-suppressing humanized monoclonal antibody designed to target CD20 B-cell surface antigens. Ocrelizumab binds to CD20 which triggers cell lysis and has been used to treat individuals diagnosed with forms of multiple sclerosis (MS). Ocrelizumab's efficacy is thought to lie in its potential ability to preserve B-cell reconstitution and long-term immune memory.

Note: Please see the following related documents for additional information:

Position Statement

Medically Necessary:

  1. Ocrelizumab is considered medically necessary for the treatment of primary progressive multiple sclerosis (PPMS) in individuals who meet all of the following criteria:
    1. Diagnosed with PPMS in accordance with the McDonald Criteria; and
    2. 18 years of age or older; and
    3. Able to ambulate more than 5 meters (not considered wheelchair bound).
  2. Ocrelizumab is considered medically necessary for the treatment of relapsing multiple sclerosis (RMS) in individuals who meet all of the following criteria:
    1. Diagnosed with RMS in accordance with the McDonald Criteria; and
    2. 18 years of age or older; and
    3. Able to ambulate without aid or rest for at least 100 meters.

Not Medically Necessary:

Ocrelizumab is considered not medically necessary as a treatment for RMS or PPMS when either of the following contraindications is present:

  1. Diagnosis of active hepatitis B or hepatitis C virus infection;
  2. A history of life-threatening infusion reaction to ocrelizumab.

Investigational and Not Medically Necessary:

Ocrelizumab is considered investigational and not medically necessary as a treatment for RMS or PPMS when the criteria above are not met and for all other indications, including but not limited to the following:

  1. Treatment of secondary progressive multiple sclerosis;
  2. Individuals with a relapsing form of MS who have not experienced at least two relapses* within the previous 2 years, or one relapse within the previous year;
  3. Systemic lupus erythematosus;
  4. Rheumatoid arthritis.

*Defined in the McDonald Criteria below.

Rationale

On March 28, 2017, ocrelizumab received Food and Drug Administration (FDA) approval as a therapy for individuals with primary progressive and relapsing forms of multiple sclerosis (FDA Product Information [PI] Label, 2017). The FDA approval of ocrelizumab for relapsing MS (RMS) was based on two identically designed Phase III double-blind, double-dummy randomized controlled trials, OPERA I and II. Approval for primary progressive MS (PPMS) was based on a randomized, double-blind, placebo-control Phase III clinical trial, ORATORIO.

In the OPERA I and II trials, 1656 study participants (18-55 years of age) were randomized 1:1 to receive ocrelizumab or interferon Beta-1a (IFN β -1a) via intravenous (IV) infusion every 6 months. Placebo injections matching subcutaneous IFN β-1a were given 3 times per week in the ocrelizumab arm and IV infusions matching ocrelizumab were administered every 6 months in the IFN β-1a arm. Notable inclusion criteria included diagnosis of MS according to the revised McDonald criteria (Polman, 2011), at least two documented clinical attacks within the last 2 years prior to screening or one clinical attack in the year prior to screening (but not within the most recent 30 days), neurologic stability for at least the past 30 days at baseline and expanded disability status scale (EDSS) score of 0-5.5. Exclusion criteria included diagnosed with PPMS, EDSS score of < 2.1 with a disease duration over 10 years, immunosuppression, and active infection. The primary endpoint in the studies was the annualized relapse rate at week 96 (2 years). Secondary endpoints included confirmed disability progression (CDP) at weeks 12 and 24 and the number of new or enhancing T1 and T2 lesions as seen on MRI at weeks 24, 48 and 96. Over 85% of those enrolled in the ocrelizumab arm completed the studies. Only 82.7% of interferon β-1a subjects in OPERA I and 76.6% of subjects in OPERA II completed their course of treatment. The superior efficacy of ocrelizumab in reducing the annualized relapse rate and disability progression was demonstrated and sustained compared to standard of care IFN β -1a at week 96. In both OPERA I and II, the annualized relapse rate was 16% compared to 29% in the subjects treated with IFN β -1a (absolute risk reduction 13%, number needed to treat 8, 46% relative risk reduction; p<0.001). The secondary endpoint of a reduction in CDP was also met at week 24 (Hazard Ratio [HR]=0.60, p=0.003). Additionally, the secondary endpoints of a reduction in T1 Gd+ lesions and new/enlarging T2 lesions were also significantly reduced in ocrelizumab arms (p<0.0001). There was no significant difference detected in the quality of life between the two arms. The most common adverse event (AE) associated with ocrelizumab was infusion-related reactions (0.01% were life-threatening and 1.3% withdrew during the first infusion). During the studies, 3 deaths occurred, 2 in the IFN β-1a arm (due to suicide and mechanical ileus) and 1 in the ocrelizumab arm (due to suicide). A total of 6 malignant neoplasms were reported (2 in the IFN β-1a arm [0.2%] and 4 [1.3%] in the ocrelizumab arm). Overall, in OPERA I and OPERA II, ocrelizumab had a similar safety profile compared with IFN β-1a over 96 weeks (Hauser, 2017). Caution is urged in the use of ocrelizumab due to higher than expected risks of herpes reactivation and cancers. Additional phase IV trials and community surveillance is warranted to further characterize risks associated with ocrelizumab administration as a treatment for MS.

ORATORIO evaluated the efficacy and safety of ocrelizumab (n=488; 600 mg administered via IV infusion every 6 months) compared to placebo (n=244) in 732 individuals (18-55 years of age) diagnosed with PPMS who were randomized 2:1. The primary outcome of interest was time to onset of sustained disability progression, defined as an increase in EDSS score that is sustained for at least 12 weeks. Secondary outcomes included interim analysis of the primary outcome at 24 weeks, change in 25-foot walk test from baseline to 120 weeks, and change in volume of T2 brain lesions on MRI. Inclusion criteria included a diagnosis of PPMS as defined by the McDonald criteria (Polman, 2011) and EDSS score of 3 to 6.5. Those with a history of relapsing forms of MS or secondary progressive MS (SPMS) were excluded as were those with other neurologic disorders, active infection, previous treatment with B-cell targeted therapies (for example, rituximab, ocrelizumab or ofatumumab) or lymphocyte trafficking blockers (for example, alemtuzumab, methotrexate, or cyclophosphamide) and comorbidities that may require chronic immunosuppressive therapy. The study's primary endpoint was met. A total of 32.9% of subjects in the ocrelizumab arm experienced disability progression lasting 12 weeks or longer compared to 39.3% of subjects in the placebo arm (absolute risk reduction, 6.4%; number needed to treat, 16; HR=0.76, 95% Confidence Interval [CI], 0.59-0.98; p=0.03). A total of 29.6% of ocrelizumab subjects experienced disability lasting 24 weeks or longer compared to 35.7% of the subjects receiving placebo injections (absolute risk reduction 6.1%, NNT=17, HR=0.75, 95% CI, 0.58-0.98; p=0.04). At week 120, 402 individuals (82%) in the ocrelizumab group and 174 individuals (71%) in the placebo group were available for analysis. There was a statistically significant reduction in the progression rate of 25-foot walk time from baseline to week 120 (55.1% change from baseline in placebo and 38.9% change from baseline in the ocrelizumab arm, absolute risk reduction 16.2%, relative risk reduction=29.3% [95% CI, -1.6 to 51.5), p=0.04). The secondary endpoints of reduction in T2 brain lesion volume (mean percent change -3.4 vs +7.4; p<0.0001) as well as the rate of whole brain volume loss (-0.90 vs. -1.09; p=0.02) also favored ocrelizumab over placebo at week 120. The mean treatment duration was approximately 3 years, during which time the proportion of study participants experiencing AEs and serious AEs associated with ocrelizumab, was similar to placebo. The most serious events were mild-to-moderate infusion-related reactions. A notable potential safety concern was that 2.3% of the ocrelizumab arm (n=11; 4 breast cancer, 3 basal cell carcinoma, and 1 each of endometrial adenocarcinoma, anaplastic large cell lymphoma, malignant fibrous histiocytoma, and pancreatic carcinoma) were diagnosed with a malignant neoplasm while only 0.8% (n=2) of the placebo arm were diagnosed with a malignant neoplasm. The differential development of neoplasms is also continuing to be investigated in individuals with PPMS (Montalban, 2016).

Ocrelizumab has not been studied in individuals diagnosed with secondary progressive multiple sclerosis (SPMS).

Background/Overview

Multiple Sclerosis

According to the National Institute of Neurological Disorders and Stroke (NINDS, 2016), there are currently 250,000 to 350,000 people in the US diagnosed with MS. This estimate includes approximately 200 new cases diagnosed every week. Studies of the prevalence of individuals with MS indicate that the rate of the disease has increased steadily during the twentieth century.

MS is an autoimmune disease of the central nervous system (CNS). During the MS disease process, inflammation of nervous tissue causes the loss of myelin, a fatty material that acts as a protective insulation for the nerve fibers in the brain and spinal cord. This demyelination leaves multiple areas of hard scarred tissue (plaques) along the covering of the nerve cells. Another characteristic of MS is the destruction of axons, which are the long filaments that carry electric impulses away from a nerve cell. The demyelination and axon destruction disrupts the ability of the nerves to conduct electrical impulses to and from the brain, and produces the various symptoms. Common symptoms of the disease include fatigue, weakness, numbness, coordination and balance problems, bowel and bladder dysfunction, emotional and cognitive changes, spasticity, vision problems, dizziness, sexual dysfunction, and pain. Classifications of MS are RRMS, PPMS, progressive relapsing (PRMS), and SPMS. Most individuals with MS have a relapsing course and their first attack may present as a clinically isolated syndrome (CIS). A CIS is a single demyelinating episode with consistent MRI findings (indicating inflammation/demyelination in one or more sites in the CNS). Individuals with this syndrome are at high risk for developing clinically definite MS.

Approximately 85% of individuals diagnosed with MS start with a relapsing course, which is known as RRMS.  The majority of individuals whose disease first presents as RRMS, will eventually develop progressive symptoms without remissions, known as SPMS. The average length of time from initial diagnosis to development of a progressive disease course is 20 years. Approximately 15% of MS presents with a progressive disease course from the first onset of illness, this is known as PPMS.

Diagnostic criteria for MS have evolved in recent years. Although the diagnosis can be made on clinical grounds alone, MRI of the CNS can support, supplement, or even replace some clinical criteria (Polman, 2011). The McDonald Criteria, a tool for the diagnosis of MS, was updated in 2010 by the International Panel on Diagnosis of MS (The Panel). The Panel stressed that the McDonald criteria should only be applied in those individuals who present with a typical CIS suggestive of MS or symptoms consistent with a CNS inflammatory demyelinating disease. This is because the development and validation of the criteria was limited to individuals with such a presentation. The 2010 McDonald criteria include clinical presentations as well as additional data needed for MS diagnosis, such as MRI findings for demonstration of dissemination of CNS lesions in space and time. The 2010 revision of the MacDonald criteria provides guidance to distinguish Acute Disseminated Encephalomyelitis (ADEM) from MS in children. It also recommends testing for AQP4 antibodies to distinguish Neuromyelitis Optica (NMO) from MS in Asian and Latin Americans.

The treatment of MS varies depending upon individual disease characteristics. RRMS is the most common type and is characterized by clearly defined exacerbations followed by periods of remission. There is no clinically-obvious disease progression during the periods between relapses. RRMS is generally associated with a better prognosis than progressive disease courses. Certain immunomodulatory agents, including interferon beta preparations, glatiramer acetate, natalizumab, fingolimod, dimethyl fumarate, alemtuzumab, daclizumab and teriflunomide, have shown beneficial effects for individuals with RRMS, including a decreased relapse rate and a slower accumulation of brain lesions on MRI.
The progressive forms of MS (SPMS and PPMS) are more difficult to treat than RRMS. Other agents approved for the treatment of RMS have not demonstrated sustained efficacy in the treatment of PPMS. Ocrelizumab is the first FDA-approved pharmacologic therapy for PPMS.

The 2010 McDonald Criteria for Diagnosis of MS
 (Polman, 2011)

Clinical Presentation

Additional Data Needed for MS Diagnosis

2 or more attacksa ; objective clinical evidence of 2 or more lesions or objective clinical evidence of 1 lesion with reasonable historical evidence of a prior attackb .

None

 

2 or more attacksa ; objective clinical evidence of one lesion

 

Dissemination in space, demonstrated by:

  • 1 or more T2 lesion in at least 2 of 4 MS-typical regions of the CNS (periventricular, juxtacortical, infratentorial, or spinal cord)d ; or
  • Await further clinical attacka implicating a different CNS site

1 attacka ; objective clinical evidence of two or more lesions

 

Dissemination in time, demonstrated by:

  • Simultaneous presence of asymptomatic gadolinium-enhancing and nonenhancing lesions at any time; or
  • A new T2 and/or gadolinium-enhancing lesion(s) on follow-up MRI, irrespective of its timing with reference to a baseline scan; or
  • Await a second clinical attacka  

1 attacka ; objective clinical evidence of one lesion (clinically isolated syndrome)

 

Dissemination in space and time, demonstrated by:
For dissemination in space (DIS):

  • 1 or more T2 lesion in at least 2 of 4 MS-typical regions of the CNS (periventricular, juxtacortical, infratentorial, or spinal cord)d ; or
  • Await a second clinical attacka implicating a different CNS site; and

For dissemination in time (DIT), demonstrated by:

  • Simultaneous presence of asymptomatic gadolinium-enhancing and nonenhancing lesions at any time; or
  • A new T2 and/or gadolinium-enhancing lesion(s) on follow-up MRI, irrespective of its timing with reference to a baseline scan; or
  • Await a second clinical attacka

Insidious neurological progression suggestive of MS (typical presentation of PPMS)

 

1 year of disease progression (retrospectively or prospectively determined) plus 2 of 3 of the following criteriad :

  1. Evidence for DIS in the brain based on one or more T2 lesions in the MS-characteristic (periventricular, juxtacortical, or infratentorial) regions
  2. Evidence for DIS in the spinal cord based on 2 or more T2 lesions in the cord
  3. Positive CSF (isoelectric focusing evidence of oligoclonal bands and/or elevated IgG index)

If the Criteria are fulfilled and there is no better explanation for the clinical presentation, the diagnosis is ''MS''; if suspicious, but the Criteria are not completely met, the diagnosis is ''possible MS''; if another diagnosis arises during the evaluation that better explains the clinical presentation, then the diagnosis is ''not MS.''
a An attack (relapse; exacerbation) is defined as self-reported or objectively observed events typical of an acute inflammatory demyelinating event in the CNS, current or historical, with duration of at least 24 hours, in the absence of fever or infection. It should be documented by contemporaneous neurological examination, but some historical events with symptoms and evolution characteristic for MS, but for which no objective neurological findings are documented, can provide reasonable evidence of a prior demyelinating event. Reports of paroxysmal symptoms (historical or current) should, however, consist of multiple episodes occurring over not less than 24 hours. Before a definite diagnosis of MS can be made, at least 1 attack must be corroborated by findings on neurological examination, visual evoked potential response in individuals reporting prior visual disturbance, or MRI consistent with demyelination in the area of the CNS implicated in the historical report of neurological symptoms.
b Clinical diagnosis based on objective clinical findings for 2 attacks is most secure. Reasonable historical evidence for 1 past attack, in the absence of documented objective neurological findings, can include historical events with symptoms and evolution characteristics for a prior inflammatory demyelinating event; at least 1 attack, however, must be supported by objective findings.
c No additional tests are required. However, it is desirable that any diagnosis of MS be made with access to imaging based on these Criteria. If imaging or other tests (for instance, CSF) are undertaken and are negative, extreme caution needs to be taken before making a diagnosis of MS, and alternative diagnoses must be considered. There must be no better explanation for the clinical presentation, and objective evidence must be present to support a diagnosis of MS.
d Gadolinium-enhancing lesions are not required; symptomatic lesions are excluded from consideration in subjects with brainstem or spinal cord syndromes.

MS = multiple sclerosis; CNS = central nervous system; MRI = magnetic resonance imaging; DIS = dissemination in space; DIT = dissemination in time; PPMS = primary progressive multiple sclerosis; CSF = cerebrospinal fluid; IgG = immunoglobulin G.

2010 McDonald MRI Criteria for Demonstration of DIS:
DIS can be demonstrated by one or more T2 lesiona in at least two of four areas of the CNS:

  1. Periventricular
  2. Juxtacortical
  3. Infratentorial
  4. Spinal cordb

Based on Swanton et al 2006, 2007.
a Gadolinium enhancement of lesions is not required for DIS.
b If a subject has a brainstem or spinal cord syndrome, the symptomatic lesions are excluded from the Criteria and do not contribute to lesion count.
MRI = magnetic resonance imaging; DIS = dissemination in space; CNS = central nervous system

2010 McDonald MRI Criteria for Demonstration of DIT:
DIT can be demonstrated by:

  1. A new T2 and/or gadolinium-enhancing lesion(s) on follow-up MRI, with reference to a baseline scan, irrespective of the timing of the baseline MRI
  2. Simultaneous presence of asymptomatic gadolinium-enhancing and nonenhancing lesions at any time

Based on Montalban et al 2010.
MRI = magnetic resonance imaging; DIT = dissemination in time.

2010 McDonald Criteria for Diagnosis of Multiple Sclerosis in Disease with Progression from Onset:

  1. One year of disease progression (retrospectively or prospectively determined)
  2. Plus two of the three following criteriaa :
    1. Evidence for DIS in the brain based on one or more T2b lesions in at least one area characteristic for MS (periventricular, juxtacortical, or infratentorial)
    2. Evidence for DIS in the spinal cord based on two or more T2b lesions in the cord
    3. Positive CSF (isoelectric focusing evidence of oligoclonal bands and/or elevated IgG index)

a If a subject has a brainstem or spinal cord syndrome, all symptomatic lesions are excluded from the Criteria.
b Gadolinium enhancement of lesions is not required.
MS = multiple sclerosis; PPMS = primary progressive multiple sclerosis; DIS = dissemination in space; CSF = cerebrospinal fluid; IgG = immunoglobulin G.

 

PPMS may be diagnosed in subjects with:  (Polman 2011)
  1. One year of disease progression (retrospectively or prospectively determined)
  2. Plus 2 of the 3 following criteriaa :
    1. Evidence for DIS in the brain based on ≥ 1 T2b lesion in at least one area characteristic for MS (periventricular, juxtacortical or infratentorial)
    2. Evidence for DIS in the spinal cord based on ≥ 2 T2 lesions in the cord.
    3. Positive CSF (isoelectric focusing evidence of oligoclonal bands and/or elevaed IgG Index. 

a If a subject has a brainstem or spinal syndrome, all symptomatic lesions are excluded from the Criteria.
b Gadolinium enhancement of lesions is not required.
MS = multiple sclerosis; PPME = primary progressive multiple sclerosis; DIS = dissemination in space; CSF = cerebral spinal fluid; IgG = immunoglobulin G

Adverse Events and Warnings

Warnings and precautions from the FDA PI Label (2017) include the following:

Additional Warnings from the FDA PI Label (2017) include:

Definitions

Clinical lesion: An area of inflamed or demyelinated central nervous system tissue; synonymous with plaque.

Expanded Disability Status Scale (EDSS): A method of quantifying disability in MS and monitoring changes in the level of disability over time. The scale ranges from 0 to 10 in 0.5 unit increments; increasing units represent higher levels of disability. Scoring is based on examination by a neurologist. 

Monoclonal Antibody: A protein developed in the laboratory that can locate and bind to specific substances in the body and on the surface of cancer cells.

Primary progressive MS (PPMS): A clinical course of MS characterized by progression of disability from onset without superimposed relapses. The term progressive-relapsing multiple sclerosis or PRMS, previously used to characterize individuals who had progressive disease from onset and clear acute relapses, is no longer preferred. An acute relapse in an individuals with progressive disease from onset is now considered to be PPMS with active disease, whereas those with progressive disease from onset without acute relapses are considered to have PPMS, not active but with progression.

Relapse: The appearance of new symptoms or the aggravation of old ones, lasting at least 24 hours in the absence of fever or infection (synonymous with exacerbation, attack, flare-up, or worsening); usually associated with inflammation and demyelination in the brain or spinal cord.

Relapsing MS (RMS): A clinical course of MS characterized by clearly defined, acute relapses with full or partial recovery; no disease progression or worsening of disability develops between relapses.

Secondary progressive MS (SPMS): A clinical course of MS demonstrating sustained progression of physical disability occurring separately from relapses in individuals who previously had RRMS.

Coding

The following codes for treatments and procedures applicable to this document are included below for informational purposes. Inclusion or exclusion of a procedure, diagnosis or device code(s) does not constitute or imply member coverage or provider reimbursement policy. Please refer to the member's contract benefits in effect at the time of service to determine coverage or non-coverage of these services as it applies to an individual member.

When services may be Medically Necessary when criteria are met:

HCPCS

 

J2350

Injection, ocrelizumab, 1 mg [Ocrevus]

 

 

 

ICD-10 Diagnosis

 

 

G35

Multiple sclerosis

 

When services are Not Medically Necessary:
For the procedure and diagnosis codes listed above for the situations listed in the Position Statement section as not medically necessary.

When services are Investigational and Not Medically Necessary:
For the procedure and diagnosis codes listed above when criteria are not met or for all other diagnoses not listed; or when the code describes a procedure indicated in the Position Statement section as investigational and not medically necessary.

References

Peer Reviewed Publications:

  1. Abushouk AI, Ahmed H, Ismail A, et al. Safety and efficacy of ocrelizumab in rheumatoid arthritis patients with an inadequate response to methotrexate or tumor necrosis factor inhibitors: a systematic review and meta-analysis. Rheumatol Int. 2017; 37(7):1053-1064.
  2. Filippini G, Del Giovane C, Clerico M, et al. Treatment with disease-modifying drugs for people with a first clinical attack suggestive of multiple sclerosis. Cochrane Database Syst Rev. 2017;(4):CD012200.
  3. Harigai, Tanaka Y, Maisawa S.; JA21963 Study Group. Safety and efficacy of various dosages of ocrelizumab in Japanese patients with rheumatoid arthritis with an inadequate response to methotrexate therapy: a placebo-controlled double-blind parallel-group study. J Rheumatol. 2012; 39(3):486-495.
  4. Hauser SL, Bar-Or A, Comi G, et al. Ocrelizumab versus interferon beta-1a in relapsing multiple sclerosis. N Engl J Med. 2017; 376(3):221-234.
  5. Kappos L, Li D, Calabresi PA, et al. Ocrelizumab in relapsing-remitting multiple sclerosis: a phase 2, randomised, placebo-controlled, multicentre trial. Lancet. 2011; 378(9805):1779-1787.
  6. Montalban X, Hauser SL, Kappos L, et al. Ocrelizumab versus placebo in primary progressive multiple sclerosis. N Engl J Med. 2017; 376(3):209-220.
  7. Mysler EF, Spindler AJ, Guzman R, et al. Efficacy and safety of ocrelizumab in active proliferative lupus nephritis: results from a randomized, double-blind, phase III study. Arthritis Rheum. 2013; 65(9):2368-2379.
  8. Polman CH, Reingold SC, Banwell B, et al. Diagnostic criteria for multiple sclerosis: 2010 revisions to the McDonald criteria. Ann Neurol. 2011; 69(2):292-302.
  9. Rigby W, Tony HP, Oelke K, et al. Safety and efficacy of ocrelizumab in patients with rheumatoid arthritis and an inadequate response to methotrexate: results of a forty-eight-week randomized, double-blind, placebo-controlled, parallel-group phase III trial. Arthritis Rheum. 2012; 64(2):350-359.
  10. Stohl W, Gomez-Reino J, Olech E. Safety and efficacy of ocrelizumab in combination with methotrexate in MTX-naive subjects with rheumatoid arthritis: the phase III FILM trial. Ann Rheum Dis. 2012; 71(8):1289-1296.
  11. Tak PP, Mease PJ, Genovese MC, et al. Safety and efficacy of ocrelizumab in patients with rheumatoid arthritis and an inadequate response to at least one tumor necrosis factor inhibitor: results of a forty-eight–week randomized, double-blind, placebo-controlled, parallel-group phase III trial. Arthritis Rheum. 2012; 64(2):360-370.

Government Agency, Medical Society, and Other Authoritative Publications:

  1. Hoffmann-La Roche. A study of ocrelizumab in comparison with Interferon Beta-1a (Rebif) in participants with relapsing multiple sclerosis: OPERA I. NLM Identifier: NCT01412333. Updated October 25, 2016.  Available at: https://clinicaltrials.gov/ct2/show/NCT01412333 . Accessed on June 29, 2017.
  2. Hoffmann-La Roche. A study of ocrelizumab in comparison with Interferon Beta-1a (Rebif) in participants with relapsing multiple sclerosis: OPERA II. NLM Identifier: NCT01247324. Updated October 10, 2016. Available at: https://clinicaltrials.gov/ct2/show/NCT01247324 . Accessed on June 29, 2017.
  3. Hoffmann-La Roche. A study of ocrelizumab in patients with primary progressive multiple sclerosis. NLM Identifier: NCT01194570. Updated January 6, 2017. Available at: https://clinicaltrials.gov/ct2/show/NCT01194570 . Accessed on June 29, 2017.
  4. Ocrevus™. Product Information Label. Genentech, Inc, San Francisco, CA. Updated March 28, 2017. Available at https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/761053lbl.pdf . Accessed on June 29, 2017.
Websites for Additional Information
  1. American Academy of Neurology. Multiple Sclerosis: Practice Guidelines. March 2014 Available at: https://www.aan.com/Guidelines/Home/ByTopic?topicId=18 . Accessed June 29, 2017.
  2. National Institute of Neurological Disorders and Stroke (NINDS). Multiple Sclerosis: Hope through research. Available at: https://www.ninds.nih.gov/Disorders/Patient-Caregiver-Education/Hope-Through-Research/Multiple-Sclerosis-Hope-Through-Research . Accessed on June 29, 2017.
  3. National Institute of Neurological Disorders and Stroke (NINDS). Multiple Sclerosis Information Page. Available at: https://www.ninds.nih.gov/Disorders/All-Disorders/Multiple-Sclerosis-Information-Page . Accessed on June 29, 2017.
  4. National Multiple Sclerosis Society. What is MS? Available at: http://www.nationalmssociety.org/about-multiple-sclerosis/index.aspx. Accessed June 29, 2017.
  5. Tarver, M. Kurtzke Expanded Disability Status Scale (EDSS). Department of Veterans Affairs: Multiple Sclerosis Centers for Excellence. Last Updated on June 21, 2017. Available at: http://www.va.gov/MS/Professionals/Diagnosis/Kurtzke_Expanded_Disability_Status_Scale.asp. Accessed on June 29, 2017.
Document History
Status Date Action
  12/27/2017 The document header wording updated from “Current Effective Date” to “Publish Date.” Updated Coding section with 01/01/2018 HCPCS changes; added J2350, removed C9494 deleted 12/31/2017 and NOC codes.
Revised 08/03/2017 Medical Policy & Technology Assessment Committee (MPTAC) review. Added additional criteria to the MN indications and INV/NMN statements for SLE, RA and recurrence of MS attacks. Updated Rationale, Background/Overview, Definitions and Reference sections. Updated Coding section with 10/01/2017 HCPCS changes.
New 04/11/2017 MPTAC review. Initial document development.
Preliminary Discussion 11/03/2016 MPTAC review. Pre-FDA approval review.