Ocrevus (ocrelizumab)

Ocrevus (ocrelizumab) Policy Number: 5.01.629 Last Review: 04/2018 Origination: 05/2017 Next Review: 04/2019 Policy Blue Cross and Blue Shield of Kansas City (Blue KC) will provide coverage for Ocrevus when it is determined to be medically necessary because the following criteria have been met. When Policy Topic is covered Ocrevus may be considered medically necessary when: I. Used for the treatment of primary progressive multiple sclerosis (PPMS) in individuals 18 years of age or older who have been diagnosed with PPMS in accordance with the McDonald Criteria. OR II. Used for the treatment of relapsing multiple sclerosis (RMS) in individuals 18 years of age or older who have been diagnosed with RMS in accordance with the McDonald Criteria AND Patient has had an inadequate response to one or more of the following first-line drugs indicated for the treatment of multiple sclerosis: Avonex, Rebif, Betaseron, Extavia, Copaxone, GlatopaTM (glatirmer acetate injection for SC use, or PlegridyTM (peginterferon beta-1a for SC injection). Usual Dosing: (Administered IV though a dedicated IV line using a 0.2 or 0.22 micron in-line filter) Starting dose: 300 mg IV Second dose two weeks after first dose: 300 mg IV Subsequent doses administered once every 6 months (beginning 6 months after first dose): 600 mg IV Drug must be sourced from an approved specialty infusion provider. When Policy Topic is not covered Ocrevus is considered investigational as a treatment for RMS or PPMS when the criteria above are not met and for all other indications, including but not limited to treatment for secondary progressive multiple sclerosis. Ocrelizumab is considered not medically necessary as a treatment for RMS or PPMS when either of the following contraindications is present: Diagnosis of active hepatitis B virus infection; OR A history of life-threatening infusion reaction to ocrelizumab. Considerations Ocrevus requires prior authorization through the Clinical Pharmacy Department.

This Blue Cross and Blue Shield of Kansas City policy Statement was developed using available resources such as, but not limited to: Food and Drug Administration (FDA) approvals, Facts and Comparisons, National specialty guidelines, Local medical policies of other health plans, Medicare (CMS), Local providers. Description of Procedure or Service 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, 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 RMS. 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 disease progression during the periods between disease 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. Many of the same agents used in RRMS provide temporary benefit for those with progressive disease, but their long-term use is often limited by serious and sometimes worsening side-effects. Many of these drugs have failed to show lasting benefit in clinical trials and there are few clinical trials that have observed outcomes beyond 2 or 3 years. Ocrelizumab is the first FDA-approved pharmacologic therapy for PPMS. The 2010 McDonald Criteria for Diagnosis of MS (Polman, 2011) Clinical Presentation 2 or more attacks a ; objective clinical evidence of 2 or more lesions or objective clinical evidence of 1 lesion with reasonable historical evidence of a prior attack b. 2 or more attacks a ; objective clinical evidence of one lesion None c Additional Data Needed for MS Diagnosis 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 attack a implicating a different CNS site 1 attack a ; objective clinical evidence of two or more lesions Dissemination in time, demonstrated by: Simultaneous presence of asymptomatic gadoliniumenhancing 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 attack a 1 attack a ; 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 attack a implicating a different CNS site; and For dissemination in time (DIT), demonstrated by: Simultaneous presence of asymptomatic gadoliniumenhancing 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 attack a Insidious neurological progression 1 year of disease progression (retrospectively or prospectively

suggestive of MS (typical presentation of PPMS) determined) plus 2 of 3 of the following criteria d : 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 lesion a in at least two of four areas of the CNS: 1. Periventricular 2. Juxtacortical 3. Infratentorial 4. Spinal cord b 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 = lesion 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 = lesion 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 criteria a : A. Evidence for DIS in the brain based on one or more T2 b lesions in at least one area characteristic for MS (periventricular, juxtacortical, or infratentorial) B. Evidence for DIS in the spinal cord based on two or more T2 b lesions in the cord C. 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 MS; DIS = lesion 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 criteria a : A. Evidence for DIS in the brain based on 1 T2 b lesion in at least one area characteristic for MS (periventricular, juxtacortical, or infratentorial) B. Evidence for DIS in the spinal cord based on 2 T2 lesions in the cord. C. Positive CSF (isoelectric focusing evidence of oligoclonal bands and/or elevated 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; PPMS = Primary Progressive MS; DIS = lesion 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: Hepatitis B virus is a contraindication to administration of ocrelizumab; screening is required prior to first the dose.

Ocrelizumab may cause infusion reactions, including pruritus, rash, urticaria, erythema, bronchospasm, throat irritation, oropharyngeal pain, dyspnea, pharyngeal or laryngeal edema, flushing, hypotension, pyrexia, fatigue, headache, dizziness, nausea, and tachycardia. A higher proportion of those treated with ocrelizumab experienced infections compared to those taking IFN β-1a or placebo. Although no cases of progressive multifocal leukoencephalopathy (PML) were identified in ocrelizumab clinical trials, John Cunningham (JC) virus infection resulting in PML has been observed in some individuals treated with other anti-cd20 antibodies and other MS therapies. JC virus has been associated with some risk factors (for example, immunocompromised individuals, polytherapy with immunosuppressants). The safety of immunization with live or live-attenuated vaccines following ocrelizumab therapy has not been studied, and vaccination with live-attenuated or live vaccines is not recommended during treatment and until B-cell repletion. An increased risk of malignancy, including breast cancer, may exist with ocrelizumab therapy. Additional Warnings from the FDA PI Label (2017) include: In case of active infection, delay infusion of ocrelizumab until the infection resolves. Pre-medicate individuals with an antihistamine (for example, diphenhydramine) approximately 30-60 minutes prior to each ocrelizumab infusion to further reduce the frequency and severity of infusion-related reactions. The addition of an antipyretic (for example, acetaminophen) may also be considered prior to commencement of ocrelizumab infusions. Observe recipients of ocrelizumab for at least 1 hour after the completion of an infusion. Based on animal data, ocrelizumab may cause fetal harm. 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 or Rebif) 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, 2016). 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). References

Peer Reviewed Publications: 1. 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. 2. 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. 3. 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. 4. 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. 5. Morschhauser F, Marlton P, Vitolo U, Results of a phase I/II study of ocrelizumab, a fully humanized anti-cd20 mab, in patients with relapsed/refractory follicular lymphoma. Ann Oncol. 2010; 21(9):1870-1876. 6. 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. 7. 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. 8. 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. 9. 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. 10. 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, 216. Available at: https://clinicaltrials.gov/ct2/show/nct01412333. Accessed on March 28, 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 March 28, 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 March 28, 2017.

4. Ocrevus. Product Information Label. Genentech, Inc, San Francisco, CA. Updated March 28, 2017. Available at: https://www.gene.com/download/pdf/ocrevus_prescribing.pdf. Accessed on May 31, 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 March 28, 2017. 2. National Institute of Neurological Disorders and Stroke (NINDS). Multiple Sclerosis: Hope Through Research. Last Updated November 19, 2015. Available at: http://www.ninds.nih.gov/disorders/multiple_sclerosis/detail_multiple_sclerosis.htm. Accessed on March 28, 2017. 3. National Institute of Neurological Disorders and Stroke (NINDS). Multiple Sclerosis Information Page. Last Updated on November 19, 2015. Available at: http://www.ninds.nih.gov/disorders/multiple_sclerosis/multiple_sclerosis.htm. Accessed on March 28, 2017. 4. National Multiple Sclerosis Society. What is MS? Available at: http://www.nationalmssociety.org/about-multiple-sclerosis/index.aspx. Accessed March 28, 2017. 5. Tarver, M. Kurtzke Expanded Disability Status Scale (EDSS). Department of Veterans Affairs: Multiple Sclerosis Centers for Excellence. Last Updated on July 2015. Available at: http://www.va.gov/ms/professionals/diagnosis/kurtzke_expanded_disability_status_scale. asp. Accessed on March 28, 2017. Billing Coding/Physician Documentation Information Ocrevus is considered a medical benefit J3590 Unclassified biologics [when specified as ocrelizumab (Ocrevus)] C9494 Ocrevus 300 MG/10ML SOLN C9494 Injection, ocrelizumab, 1 mg (For Hospital OPPS billing prior to 10/1/17 use C9399) - see also J3590 J2350 Ocrevus 300 MG/10ML SOLN J2350 Injection, ocrelizumab, 1 mg (Code becomes effective for Medicare billing 1/1/18) (Code re-used by CMS 1/1/18) Additional Policy Key Words 5.01.629 Policy Implementation/Update Information 05/2017 New policy titled Ocrevus (ocrelizumab) 12/2017 Added C9494 and J2350 04/2018 Reviewed-no changes State and Federal mandates and health plan contract language, including specific provisions/exclusions, take precedence over Medical Policy and must be considered first in determining eligibility for coverage. The medical policies contained herein are for informational purposes. The medical policies do not constitute medical advice or medical care. Treating health care providers are independent contractors and are neither employees nor agents Blue KC and are solely responsible for diagnosis, treatment and medical advice. No part of this publication may be reproduced, stored in a retrieval system or transmitted, in any form or by any means, electronic, photocopying, or otherwise, without permission from Blue KC.