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PubMed This is a summary of 18 peer-reviewed journal articles Updated
Neurology · Multiple Sclerosis

Treatment Options: Managing Progressive MS with Medications

At a Glance

For progressive MS, ocrelizumab may help some adults with PPMS and siponimod is used for active SPMS; these medicines can slow disability or inflammatory activity but are not cures, so infection screening, monitoring, vaccination, and symptom-focused care matter.

For many years, treatment options for progressive forms of Multiple Sclerosis (MS) were very limited. Today, we have Disease-Modifying Therapies (DMTs) specifically approved to help slow the worsening of the disease [1][2].

It is important to have realistic expectations: these medications are designed to slow down the accumulation of disability and reduce the frequency of new inflammatory activity [3][4]. They are not cures, and they generally do not reverse established disability or completely halt progression [5].

Standard Treatments for Progressive MS

The choice of medication depends heavily on your specific diagnosis, age, disease duration, and safety profile.

Ocrelizumab (Ocrevus)

Ocrelizumab is an intravenous infusion given every six months. In many jurisdictions, it is indicated broadly for adults with Primary Progressive MS (PPMS), though research shows it is often most beneficial for younger patients or those with signs of active inflammation [1][6].

  • How it works: It targets and depletes a specific type of immune cell called B-cells (CD20+) that drive inflammation [7].
  • Efficacy Context: In the landmark ORATORIO clinical trial for PPMS, ocrelizumab reduced the relative risk of confirmed disability progression by approximately 24% compared to a placebo over the study period [3]. It is important to understand that this is a relative risk reduction seen across a large group in a clinical trial, not a guarantee of your individual outcome.

Siponimod (Mayzent)

Siponimod is a daily pill specifically indicated for people with Active Secondary Progressive MS (SPMS)—meaning those who are progressing but also still experiencing relapses or showing new inflammatory activity on MRI scans [2][4].

  • How it works: It is a selective sphingosine-1-phosphate (S1P) receptor modulator that “traps” certain immune cells in the lymph nodes, preventing them from entering the central nervous system [8].
  • Efficacy Context: In the EXPAND trial, siponimod reduced the relative risk of 3-month confirmed disability progression by 21% overall, with stronger effects seen in the subgroup of patients with active disease [8][4]. It also showed benefits in preserving cognitive processing speed [9].

Risks and Patient-Specific Monitoring

Because these drugs suppress parts of the immune system, they carry significant risks and require careful monitoring.

Medication Major Risks Pre-Treatment and Ongoing Monitoring
Ocrelizumab Infusion reactions, upper respiratory infections, cold sores, and potentially severe infections [3][7]. Screening for Hepatitis B and tuberculosis before starting. Your doctor may periodically monitor immunoglobulin levels (IgG/IgM) and B-cell counts depending on your clinical picture and local guidelines [10][11].
Siponimod Lymphopenia (low white blood cells), high blood pressure, liver enzyme elevation, and macular edema (eye swelling) [8][12]. CYP2C9 genotyping (a genetic test) is required to determine your dose; some genotypes are contraindicated. First-dose heart rate monitoring may be required if you have a cardiac history. Regular liver tests and eye exams are needed [12][13].

Vaccination and Serious Safety Warnings

  • Vaccinations: You must complete all necessary vaccinations (such as for Shingles/Varicella-Zoster and Hepatitis B) before starting these therapies. Live vaccines are generally contraindicated while on immunosuppressive DMTs [14][15].
  • Severe Infections: Because your immune system is altered, you may not get a typical fever when fighting a serious infection (like pneumonia or sepsis). Promptly report new severe weakness, confusion, or sudden functional decline to your care team [16].
  • PML Risk: Progressive Multifocal Leukoencephalopathy (PML) is a rare, potentially fatal brain infection [11]. The risk exists with several MS therapies, especially if you have used other immune-suppressing drugs previously [17].

Approaching ‘Non-Active’ Progression

If your MS is progressing but “non-active” (no recent relapses or new MRI spots), the use of DMTs is a complex discussion. Clinical trials have shown that current anti-inflammatory medications are much less effective in the absence of visible acute inflammation [4][18].

This does not mean you have “no options.” Instead, treatment decisions must carefully weigh the limited potential benefit against the real risks of severe infections [5]. For non-active progression, care focuses heavily on aggressive symptom management, physical rehabilitation, maintaining overall health, and exploring clinical trials for emerging neuroprotective therapies.

Common questions in this guide

Which medications are used to treat progressive MS?
Ocrelizumab is an infusion approved in many jurisdictions for many adults with primary progressive MS (PPMS). Siponimod is a daily pill for eligible people with active secondary progressive MS (SPMS), meaning progression with relapses or new inflammatory activity on MRI. A neurologist considers disease activity, age, disease duration, and safety risks when choosing treatment.
Do progressive MS medications stop or reverse disability?
No. These medicines are intended to slow the buildup of disability and reduce new inflammatory activity; they are not cures and generally do not reverse disability that is already present. They also cannot guarantee that progression will stop completely.
What safety checks are needed before starting ocrelizumab?
Before ocrelizumab, clinicians generally screen for hepatitis B and tuberculosis and review vaccination status. During treatment, the care team may monitor infections, immunoglobulin levels, and B-cell counts, depending on the person's clinical situation and local guidance. Ocrelizumab can cause infusion reactions and infections, so new or severe illness should be reported promptly.
What testing is required before taking siponimod?
Siponimod requires CYP2C9 genetic testing to help determine the dose, and some genetic profiles make it unsuitable. Depending on cardiac history, first-dose heart-rate monitoring may be needed. Regular liver tests and eye examinations help monitor for side effects such as liver enzyme changes or swelling in the eye.
Should I get vaccines before starting a progressive MS medication?
Necessary vaccinations, including shingles or varicella-zoster and hepatitis B vaccines when appropriate, should be completed before starting treatment. Live vaccines are generally avoided while taking immunosuppressive disease-modifying therapy. Ask your neurologist which vaccines you need and how long to wait before treatment.
What happens if progressive MS is non-active?
When progressive MS is non-active, meaning there are no recent relapses or new MRI lesions, current anti-inflammatory medicines may provide less benefit. Care often emphasizes symptom management, physical rehabilitation, overall health, and clinical trials of emerging neuroprotective treatments. Your neurologist can help balance possible medication benefits against infection risks.
What signs of infection should I report while taking MS medication?
Immune-suppressing MS treatments can make serious infections harder to recognize, and a typical fever may be absent. Report severe weakness, confusion, sudden functional decline, or other rapidly worsening symptoms to your care team promptly. Seek urgent medical help if symptoms are severe or life-threatening.

Questions to Ask Your Doctor

Curated prompts to bring to your next appointment.

  1. 1.Based on my diagnosis (PPMS or active SPMS), what are the approved disease-modifying therapies available to me?
  2. 2.How do you weigh the potential benefits of slowing my progression against my specific risks for severe infections?
  3. 3.What is my CYP2C9 genotype, and how does that affect my eligibility or dosing for siponimod?
  4. 4.Are my vaccinations, including for shingles and hepatitis B, fully up to date before I start a new immunosuppressive therapy?
  5. 5.If I have 'non-active' progression, what symptomatic treatments or rehabilitation programs should we focus on to maximize my function?

Questions For You

Tap a prompt to share your answer — we'll use it plus this page's context to start a tailored conversation.

References

References (18)
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    Ocrelizumab: A Review in Multiple Sclerosis.

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    PMID: 30171504
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    Gaining First Insights on Secondary Progressive Multiple Sclerosis Patients Treated With Siponimod in Clinical Routine: Protocol of the Noninterventional Study AMASIA.

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    JMIR research protocols 2020; (9(7)):e19598 doi:10.2196/19598.

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    Ocrelizumab versus Placebo in Primary Progressive Multiple Sclerosis.

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    Siponimod vs placebo in active secondary progressive multiple sclerosis: a post hoc analysis from the phase 3 EXPAND study.

    Gold R, Piani-Meier D, Kappos L, et al.

    Journal of neurology 2022; (269(9)):5093-5104 doi:10.1007/s00415-022-11166-z.

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    Ocrelizumab infusion experience in patients with relapsing and primary progressive multiple sclerosis: Results from the phase 3 randomized OPERA I, OPERA II, and ORATORIO studies.

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    Clinical Evaluation of Siponimod for the Treatment of Secondary Progressive Multiple Sclerosis: Pathophysiology, Efficacy, Safety, Patient Acceptability and Adherence.

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    Positioning siponimod and the post-treatment gap: the unmet needs of SPMS patients in Italian real-world practice.

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    Novel multiple sclerosis agents-associated cardiotoxicity: A real-world pharmacovigilance study.

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This page is for informational purposes only and does not constitute medical advice about progressive MS treatment. Your neurologist should help you weigh medication benefits, infection risks, monitoring, vaccinations, and rehabilitation based on your situation.

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