What is the role of Ocrelizumab (Ocrelizumab) in Multiple Sclerosis (MS)?

From the Guidelines

Ocrelizumab is a highly effective treatment option for both relapsing-remitting multiple sclerosis (RRMS) and primary progressive multiple sclerosis (PPMS), with significant benefits in reducing relapse rates, delaying disability progression, and decreasing the formation of new brain lesions, as demonstrated in clinical trials such as OPERA 1 and 2, and ORATORIO 1.

Key Points

• Ocrelizumab works by targeting CD20-positive B cells, which are involved in the autoimmune process that damages myelin in multiple sclerosis, and has been shown to be effective in clinical trials, including OPERA 1 and 2, where it was compared to IFNβ1a (SC) 1.
• The treatment regimen for ocrelizumab typically consists of an initial dose given as two 300mg infusions separated by two weeks, followed by 600mg infusions every six months thereafter.
• Common side effects of ocrelizumab include infusion-related reactions, which can be managed with premedication, and an increased risk of infections, particularly upper respiratory tract infections 1.
• Prior to starting treatment, patients should be screened for hepatitis B virus and should not receive live or live-attenuated vaccines while on therapy, and regular laboratory monitoring, including immunoglobulin levels and complete blood counts, is recommended during treatment.

Clinical Trial Evidence

• The OPERA 1 and 2 trials demonstrated the efficacy of ocrelizumab in reducing relapse rates and delaying disability progression in patients with RRMS, compared to IFNβ1a (SC) 1.
• The ORATORIO trial showed that ocrelizumab slowed disability progression in patients with PPMS, making it the first and only disease-modifying therapy approved for this type of multiple sclerosis 1.

Patient Monitoring and Safety

• Regular monitoring of patients on ocrelizumab is necessary to manage potential side effects and ensure safe treatment, including monitoring for infections and laboratory abnormalities 1.
• Patients should be aware of the potential risks and benefits of ocrelizumab and be educated on how to manage infusion-related reactions and other side effects.

From the FDA Drug Label

The precise mechanism by which ocrelizumab exerts its therapeutic effects in multiple sclerosis is unknown, but is presumed to involve binding to CD20, a cell surface antigen present on pre-B and mature B lymphocytes. Following cell surface binding to B lymphocytes, ocrelizumab results in antibody-dependent cellular cytolysis and complement-mediated lysis

The role of ocrelizumab in Multiple Sclerosis (MS) is to exert its therapeutic effects by binding to CD20, a cell surface antigen present on pre-B and mature B lymphocytes, resulting in antibody-dependent cellular cytolysis and complement-mediated lysis.

• Key points:
  • Ocrelizumab is a recombinant humanized monoclonal antibody directed against CD20-expressing B-cells.
  • The mechanism of action is presumed to involve binding to CD20.
  • Ocrelizumab results in antibody-dependent cellular cytolysis and complement-mediated lysis. 2

From the Research

Role of Ocrelizumab in Multiple Sclerosis

• Ocrelizumab is an intravenously administered, humanized anti-CD20 monoclonal antibody approved for the treatment of adults with relapsing forms of multiple sclerosis (RMS) or primary progressive multiple sclerosis (PPMS) 3.
• The efficacy of ocrelizumab in reducing relapse rates and disease activity in patients with RMS was demonstrated in pivotal trials and supporting single-arm studies in specific subpopulations 3.
• In patients with PPMS, ocrelizumab reduced measures of clinical and MRI progression relative to placebo 3, 4.

Mechanism of Action and Pharmacokinetics

• Ocrelizumab selectively targets CD20-positive B cells, leading to their depletion 5.
• The pharmacokinetics of ocrelizumab were described with pharmacokinetic parameters typical for an immunoglobulin G1 monoclonal antibody, with body weight as the main covariate 5.
• The extent of B-cell depletion in blood was greater with increasing ocrelizumab exposure 5.

Efficacy and Safety

• Ocrelizumab demonstrated efficacy in the treatment of relapsing and PPMS, with a significant reduction in annualized relapse rate, disability progression, and gadolinium-enhancing lesions on MRI 4.
• The subcutaneous formulation of ocrelizumab demonstrated noninferiority to the intravenous formulation regarding drug exposure, providing comparable efficacy and safety 6.
• In patients with relapsing-remitting multiple sclerosis with a prior suboptimal response to prior disease-modifying therapies, ocrelizumab led to an overall high rate of "no evidence of disease activity" (NEDA) across a wide range of disease-related and demographic subgroups 7.

Administration and Dosage

• Ocrelizumab is administered intravenously or subcutaneously, with a dosing schedule of 600 mg every 24 weeks for intravenous administration and 920 mg every 24 weeks for subcutaneous administration 3, 6.
• The subcutaneous formulation provides an additional treatment option for patients with multiple sclerosis, with comparable efficacy and safety to the intravenous formulation 6.