- Patients with active Hepatitis B or C infection
- Any severe active infection
- History of hypersensitivity reaction to ocrelizumab or its components
- Patients who have received a live vaccine within the last 6 weeks
Before Initiation of Therapy
- Have recent (<3months) cerebral MRI
- CBC, liver enzymes, creatinine, glucose,Sodium, Potassium,TSH, IGG,IGA and IGM levels, JCV index, HBsAg, anti-HBc, anti-HBs, hepatitis C. HIV, VZV serology,
- CD4+, CD8+ and CD19+ titers, IGG,IGA,IGM(ocrelizumab interferes with the anti-CD20+ assays)
- Chest Xray and/or Quantiferon for TB
- Verification of vaccination status and update if necessary
- Give Pneumococcal (prevnor and pneumovax) and Haemophilius influenza type B vaccines
- If JCV positive and switching from Natalizumab should do a CSF PCR for JCV review a recent MRI for any evidence of PML
- If switching from teriflunamide should do an 11 day wash out with cholestyramine
- If switching from fingolimod or fumarate should wait for lymphocyte recovery before initiating therapy and ensure there is no evidence of PML in a recent MRI
- Determine if there exits a predisposition to cancer especially breast cancer
- Negative pregnancy test and counsel with regards to contraception
Monitoring During Therapy
There are no official guidelines. Unknown if there is a ceiling to the cumulative use of Ocrelizumab with regards to its effect on the immune system.
- An immune status check to be done before each biannual treatment. ie: neutrophil, CD4+, CD8+ and IgG, IgA IgM levels.Mild reductions in immunoglobulin levels especially IgM can occur while grade 3 or 4 neutropenia occurred in 1 % of treated patients. Note that the median time for CD19+ level recovery was 1.5 years but could require more than 2.5 years.
- MRI Q12 months
- Neutralizing antibodies was found in only 1 patient during the clinical trials. Routine testing is not recommended.
- Increased monitoring for cancer is recommended.
- Grade 3 or 4 neutropenia
- Reduced IgG levels
- CD4+ < 250
- Severe active infection
- Severe infusion reaction
- Hypersentivity reaction to ocrelizumab
- Recurrent severe infection or recurrent lower respiratory infection or PML
Adverse Events :
- The most common (incidence ≥ 10%) adverse reactions for OCREVUS in the RRMS trials were (OCREVUS vs. IFN): infusion related reactions (IRR) (34% vs. 10%), upper respiratory tract infections (15% vs. 11%), nasopharyngitis (15% vs. 10%).
- IRR tended to occur with the first infusion and were uncommon (<10% of cases) after the fourth infusion. IRR were mild to moderate in severity in the majority of cases. An IRR that occurs after the fourth infusion and/or is increasing in severity should be considered a possible hypersensivity reaction.
- Ocrelizumab increased the risk for upper respiratory tract infections, lower respiratory tract infections, and herpes-related infections when compared to interferon therapy. There were 2 ocrelizumab related grade 4 infection during the studies. Fatal infections have been reported with Ocrelizumab and other anti-CD20 therapies.
- Although no cases of PML or hepatitis B reactivation has been reported with Ocrelizumab the latter have been associated with other anti-CD-20 therapies.
- One case case of PML has been reported in a patient who was switched from Natalizumab therapy. Caution must be exercised when switching to Ocrelizumab from any therapy with which PML is known to be associated ie Natalizumab, Fingolimod and Fumarate.
- An increased risk of malignancy with Ocrelizumab may exist. Clinical trial showed an increased incidence of cancer especially breast cancer in the ocrelizumab treated group versus control.
- The proportion of Ocrelizumab-treated patients during the studies, reporting IgG, IgA and IgM < LLN at 96 weeks was 1.5%, 2.4% and 16.5% respectively. There did not appear to be an associated increased risk of infection.
- Grade 3 (0.5 to 1.0) or 4 (<0.5) neutropenia occured in 1% of ocrelizumab treated patients.
- In the Phase II RRMS study, the median time to B-cell repletion (as per the anti-CD19+ titers) was 72 weeks (range 27 - 175 weeks). Ninety percent of all patients had their B-cells repleted to LLN or baseline by approximately two and a half years after the last infusion.
Ocrelizumab is a IgG1. Immunoglobulins are known to cross the placenta and can be found in breastmilk. Pregnancy and breasfeeding are not recommended while on therapy and for at least 6 months after the last treatment.