What disease-modifying therapy (DMT) agent is appropriate for a patient with Primary Progressive Multiple Sclerosis (MS)?

From the Guidelines

Ocrelizumab (Ocrevus) is the most appropriate disease-modifying therapy (DMT) agent to consider for a patient with Primary Progressive Multiple Sclerosis (PPMS). This recommendation is based on the latest evidence from high-quality studies, including those published in 2025 1.

Key Considerations for Ocrelizumab Use

• Ocrelizumab is specifically FDA-approved for PPMS, which distinguishes it from most other MS therapies that are only approved for relapsing forms of MS.
• The medication works by targeting CD20-positive B cells, which contribute to myelin and axonal damage in MS, thereby helping to slow the progression of disability in PPMS patients.
• Before starting treatment, patients should undergo screening for hepatitis B virus, as reactivation can occur with B-cell depleting therapies.
• Patients should complete any necessary vaccinations at least 4-6 weeks before initiating therapy, as immune responses to vaccines may be diminished after treatment.
• Common side effects include infusion reactions, increased risk of infections, and potential increased risk of malignancies, making regular monitoring for infections and infusion reactions essential during treatment.

Comparison with Other Options

• Dalfampridine (Ampyra) is not a disease-modifying therapy but rather a drug used to improve walking in patients with MS.
• Ozanimod (Zeposia) and Ofatumumab (Kesimpta) are disease-modifying therapies, but they are primarily used for relapsing forms of MS, not specifically approved for PPMS like Ocrelizumab.
• The choice of DMT should be based on the specific characteristics of the patient's disease, including the form of MS, disease activity, and the presence of any comorbidities.

Evidence Supporting Ocrelizumab

High-efficacy DMTs, including monoclonal antibodies like ocrelizumab, are more effective when treatment is initiated early 1. Ocrelizumab's efficacy in slowing disability progression in PPMS patients has been demonstrated in clinical trials, making it a preferred choice for this patient population. Regular monitoring and management of potential side effects are crucial to ensure the safe use of ocrelizumab.

Given the information provided and the focus on PPMS, Ocrelizumab (Ocrevus) stands out as the most appropriate option for managing Primary Progressive Multiple Sclerosis, considering its specific approval for this condition and its mechanism of action targeting the underlying pathology of MS.

From the FDA Drug Label

OCREVUS ZUNOVO is indicated for the treatment of: Primary progressive MS, in adults

The appropriate DMT agent to consider for a patient with Primary Progressive Multiple Sclerosis (MS) is Ocrelizumab (Ocrevus).

• Key points:
  • Ocrelizumab is indicated for the treatment of Primary Progressive MS in adults.
  • It is essential to follow the dosage and administration instructions, as well as perform the required assessments prior to treatment initiation and every dose.
  • Patients should be closely monitored during injections, and medical support should be readily available to manage severe injection reactions. 2

From the Research

Disease-Modifying Therapy (DMT) Agents for Primary Progressive Multiple Sclerosis (PPMS)

The patient, JM, has been diagnosed with Primary Progressive Multiple Sclerosis (PPMS) and is presenting with gait disturbance and loss of balance. His magnetic resonance imaging (MRI) shows a high T2 burden of disease with multiple lesions in multiple locations in the brain. Considering his diagnosis, the appropriate DMT agent to consider would be:

• Ocrelizumab (Ocrevus): As stated in the studies 3, 4, ocrelizumab is the only disease-modifying therapy (DMT) approved for PPMS. It has been shown to reduce disability progression and disease activity in patients with PPMS.

Comparison of DMT Agents

Comparing the options provided:

• A Dalfampridine (Ampyra): Not a DMT, but a medication used to improve walking in patients with MS.
• B Ozanimod (Zeposia): Approved for relapsing forms of MS, but not specifically for PPMS.
• C Ocrelizumab (Ocrevus): Approved for PPMS and relapsing forms of MS.
• D Ofatumumab (Kesimpta): Approved for relapsing forms of MS, but not specifically for PPMS.

Key Points

• Ocrelizumab has been shown to be effective in reducing disability progression and disease activity in patients with PPMS 3, 4.
• Ocrelizumab is generally well-tolerated, with a safety profile comparable to other DMTs 5, 6.
• Patients initiating ocrelizumab have superior persistence and adherence compared to other DMTs 7.