Contraindications :
  • Patients with active Hepatitis B or C infection or any severe active infection or latent/active untreated TB
  • Any active malignancy
  • Prior or familial predisposition to breast cancer
  • History of hypersensitivity reaction to ocrelizumab or its components
  • Patients who have received a live vaccine within the last 6 weeks
  • Patients who are immunocompromised

Before Initiation of Therapy
  • Have recent (<3months) cerebral MRI
  • CBC, ALT, AST, LDH, bilirubin, IgG, IgA and IgM levels, JCV index, HepBsAg, HepBcAb, HepBsAb, Hepatitis C. HIV, VZV and measles serology
  • CD4+, CD8+ and CD19+ titers,
  • ‍Chest Xray and/or Quantiferon for TB
  • Verification of vaccination status and update if necessary at least 4 weeks prior to initiating anti CD20 therapy
  • Give Pneumococcal (Prevnar 20) and Haemophilus Influenza type B and Shingles vaccines at least 4 weeks prior to initiating anti CD20 therapy
  • If JCV positive and switching from Natalizumab should do a CSF PCR for JCV  and a recent MRI for any evidence of PML
  • If switching from teriflunomide should do an 11 day washout with cholestyramine 8gm Q8H
  • If switching from natalizumab or fingolimod treatment should be initiated within 2months of stopping previous therapy to avoid possible rebound
  • negative pregnancy test and current effective anticontraception
  • avoid live vaccines for at least 6 weeks prior to initiation of, during and for 6 months post last treatment
  • determine personal and family history of breast cancer
Monitoring During Therapy
  • CBC, IgG, IgM,  every 6 months done in the month prior subsequent IV treatment
  • CD19+ at 4 months post initiation and at  9, 12 and 18 months post discontinuation or until B cell recovery or if there is loss of disease control during treatment to determine if there is ongoing B cell suppression ( rare cases of neutralizing ab were reported)
  • CD4+, CD8+ every 12 months
  • MRI Q12 months
Hold Therapy
  • neutropenia grade 3 or more ( less then 0.5)
  • IgG less than 3.5 gm/L
  • ‍CD4+ < 250
  • lymphopenia grade 3 or more ( less than 0.5)
  • serious active infection
  • do not administer if patient has an active infection or if the solution contains visible particles or is cloudy
Discontinue Therapy
  • severe injection related reaction
  • recurrent  serious infections or occurrence of severe opportunistic infection ( viral encephalitis, disseminated zoster, PML)
  • should discontinue treatment at least 6 months prior to becoming pregnant and avoid during breastfeeding
  • hypersensitivity reaction ( suspect if infusion related reaction is more severe than previous ones)
  • severe mucocutaneous reactions
  • cancer


(Some studies only include abstracts)

Product Monograph

Specific Concerns


Ocrevus trials should an incidence of reduced IgM 16.5%, IgG 2.4%, grade 3 neutropenia or lymphopenia 1%. The most common adverse event were infections especially upper and lower respiratory tract infections, cellulitis and herpetic infections. Life-threatening or fatal infections occurred in 2% of Ocrevus treated PPMS patients and 0.2% in RRMS patients. Proper patient selection, preparation and monitoring is warranted. Progressive Multifocal Leukoencephalopathy cases in patients without prior exposure to natalizumab or other immunosuppressants avec been reported therefore JCV status should be determined at treatment onset.


Ocrevus has been shown to significantly reduce humoral response to both vaccine boosters and  vaccines to new pathogens. Live vaccines are also contraindicated 6 weeks prior to initiating, during and for 6months from the last treatment. Determining vaccination status and supplementation with other vaccines for pneumococcus, Hemophilus Influenza type B and VZV is warranted.


Human IgG readily crosses the placenta and into breastmilk. Neonates born to Ocrevus treated monkeys during pregnancy showed B cell depletion as well as renal, bone marrow and testicular toxicity with increased perinatal mortality. The incidence during the Ocrevus trials, of any birth defect was 12.5% (6/48) and structural defects 6.3% (3/48). It is therefore recommended to discontinue Ocrevus at least 6 months prior to initiating pregnancy and avoiding during breastfeeding.

Breast Cancer

The incidence during the Ocrevus trials of breast cancer was for PPMS 1.7% and 0.4% in RRMS as compared to 0 in the placebo and INF treated control populations. Patients with prior or family history of breast cancer should be discouraged from initiating Ocrevus treatment.

Autoimmune diseases

Post marketing reports revealed cases of immune mediated colitis in patients within weeks to years of Ocrevus treatment initiation. Cases of oral lichen planus were reported during the Ocrevus trials and from case reports with rituximab treated patients.

Primary Progressive Multiple Sclerosis

The Olympus trial which compared rituximab to placebo in PPMS patients failed to show any benefit in reducing confirmed disability progression. Subgroup analysis however showed that patients aged less than 51 years with gadolinium enhancing lesions benefited from rituximab (HR=0.33; p=0.009) compared to placebo. The mean age of patients in the Ocrevus PPMS trial was 44years and more than 20% of patients had gadolinium enhancing lesions at baseline. The 12 and 24 weeks confirmed disability progression endpoints both showed a relative risk reduction of 24% in favor of the Ocrelizumab treated group. The Hazard Ratio was 0.6 with however 95% confidence intervals that approached 1 (0.6 -0.98). In sensitivity analysis if patients with initial progression who dropped out prior to having their disability confirmed were assigned no evidence of progression then the results became non significant with HR=0.8 (0.6-1.07; p=0.147). The Kaplan Meyer curves of disability progression separate early but then remain parallel which may suggest that the benefit occurred early on in a subgroup of patients but did not generalize to others. The benefit from Ocrevus in PPMS patient population is therefore either very modest or non existent. This should be taken into account when attempting to determine the risk benefit equation for an individual with PPMS.


Anti-CD20 therapies have been associated with higher odds ratio of hospitalization and ICU admission. Several case reports have described a prolonged relapsing course of the SARS-CoV-2 infection. Ocrevus treated MS patients, especially those with other COVID risk factors ie older age, higher disability and having associated comorbidities should, when infected by SARSCoV2, be treated with Paxlovid for 5-10 days or longer if needed.