Multiple sclerosis Ocrevus protocol and monitoring

Ocrelizumab, used for B cell depletion, has risks of infusion reactions, infections, and lymphopenia. It's contraindicated in active hepatitis and post-live vaccines. Premedication and thorough pre-therapy assessments, including MRIs and blood tests, are essential. Ongoing monitoring involves blood tests, immune status, and annual MRIs.

General Information

Ocrelizumab is a recombinant human anti-CD20 monoclonal antibody designed to optimise B cell depletion. (1) The most common adverse events with ocrelizumab are infusion related reactions, respiratory tract infections, lymphopenia, skin infections and reactivation of hepatitis B. Ocrelizumab is contraindicated in patients with active hepatitis B virus infection. Live vaccines are not recommended during ocrelizumab treatment.

Contraindications

Patients with active Hepatitis B or C infection, severe active infections and live vaccine within the last 6 weeks. (2, 3)

Premedication

The initial dose of ocrelizumab is a 300 mg IV infusion, followed two weeks later by a second 300 mg IV infusion. Subsequently, ocrelizumab is given as 600 mg IV infusion every six months.

Premedication is recommended with methylprednisolone 100mg IV, an antihistamine, such as, chlorphenramine 10 mg IV and an antipyretic (paracetamol 1gm orally).

Monitor

Before Initiation of Therapy:

Have recent (<3months) cerebral MRI

CBC, liver enzymes, creatinine, glucose,sodium, potassium,TSH, immunoglobulin level, JCV index, HBsAg, anti-HBs, anti-HBc, hepatitis C. HIV, VZV serology,

CD4+, CD8+ and CD19+ titers (ocrelizumab interferes with the anti-CD20+ assays)

Chest Xray and/or Quantiferon for TB

Verification of vaccination status and update if necessary. Give Pneumococcal and Haemophilius influenza type B vaccines.

If JCV positive and switching from Natalizumab should do a CSF PCR for JCV with MRI for any evidence of PML;

If switching from teriflunamide should have 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 is a predisposition to cancer especially breast cancer Negative pregnancy test and counsel with regards to contraception

Monitoring During Therapy

CBC, liver enzymes, creatinine, glucose,sodium, potassium,TSH,

An immune status check to be done before each biannual treatment including CD4+, CD8+ and immunoglobulin levels.

MRI yearly

(4, 5, 6, 7)

References

1-Calabresi PA. B-Cell Depletion - A Frontier in Monoclonal Antibodies for Multiple Sclerosis. N Engl J Med 2017; 376:280.

2- Hwang JP, Somerfield MR, Alston-Johnson DE, et al. Hepatitis B virus screening for patients with cancer before therapy: American Society of Clinical Oncology provisional clinical opinion update. J Clin Oncol. 2015;33(19):2212-2220.

3-Luna G, Alping P, Burman J, et al. Infection Risks Among Patients With Multiple Sclerosis Treated With Fingolimod, Natalizumab, Rituximab, and Injectable Therapies. JAMA Neurol 2019.

4- Juanatey A, Blanco-Garcia L, Tellez N. Ocrelizumab: its efficacy and safety in multiple sclerosis. Rev Neurol. 2018;66(12):423-433.

5-Rae-Grant A, Day GS, Marrie RA, et al. Practice guideline recommendations summary: Disease-modifying therapies for adults with multiple sclerosis: Report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology [published correction appears in Neurology. 2019;92(2):112]. Neurology. 2018;90(17):777-788.

6- Ocrevus (ocrelizumab) [product monograph]. Mississauga, Ontario, Canada: Hoffmann-La Roche Limited; April 2019.

7- Ocrevus (ocrelizumab) prescribing information. https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/761053s02 4lbl.pdf (Accessed on July 27, 2020).