Doctors have traditionally used a "step-up," also known as the "escalation," approach for treating multiple sclerosis (MS), the neurodegenerative disease that affects the central nervous system. Using this approach, neurologists often prescribe a first-line therapy that is less effective, but is perceived to be safer. Then, if new MS symptoms consistent with an MS relapse occur or an MRI reveals new damage to the brain or spinal cord, treatment is ramped up to a more effective medication.
Some doctors, however, have moved away from starting treatment with the traditional first-line therapies. Instead, they favor starting with early aggressive treatment when patients first receive an MS diagnosis. That's because some recent studies have shown that the newer, more effective MS treatments can have a positive long-term impact on patients when they start taking them soon after diagnosis, instead of starting with a less effective treatment and waiting for the disease to worsen, resulting in potential irreversible physical or cognitive disability.
The rationale for this approach is that neurologists want to prevent any new damage to the brain and spinal cord at the earliest time point to prevent patients from losing physical function and having worsening memory over time. This is because damage in the brain and spinal cord from MS is often irreversible.
MS causes the most inflammation early in the course of the disease, often at younger ages, and then inflammation tends to decrease over time as a person ages, researchers found. Reducing the buildup of brain and spinal cord damage during the early stages of MS may lead to improved long-term clinical outcomes over a person's lifetime. Still, those authors noted, as yet there is no way to predict for sure whether a specific MS therapy will help an individual patient more than another.
Re-evaluating Safety
Authors of a 2024 article in the Journal of Neurology explained that for the last 25 years, it was widely accepted that so-called lower-efficacy therapies have a better safety profile than higher-efficacy treatments. "However, closer scrutiny of the safety of injectable drugs suggests that this is not entirely the case," the team wrote.
For example, the first-line therapy interferon-beta is well known for its common flu-like side effects. People who take interferon-beta are also more likely to have reduced blood cell counts, thyroid problems, and, possibly, depression, which is already a concern for people with MS.
Similarly, the traditional first-line therapy glatiramer (Copaxone) can cause rashes, skin necrosis, and low white blood cell counts. Common side effects from the first-line therapy teriflunomide (Aubagio), include diarrhea, nausea, increased liver enzyme levels, and interstitial lung disease.
The higher-efficacy therapies for MS have the reputation of causing more -- and more serious -- side effects, although recent studies have shown them to be less likely to cause severe side effects than initially believed. These treatments include:
- Ozanimod (Zeposia) and other sphingosine-1-phosphate modulators: fingolimod (Gilenya), siponimod (Mayzent), ponesimod (Ponvory)
- Natalizumab (Tysabri)
- Anti-CD20 monoclonal antibodies: ocrelizumab (Ocrevus), ublituximab (Briumvi), ofatumumab (Kesimpta), rituximab (Rituxan) (off-label)
- Alemtuzumab (Lemtrada)
- Cladribine (Mavenclad)
Regardless of whether your medical team favors escalation or early aggressive treatment, there are a few common principles when prescribing MS treatments. These include the following, according to researchers at Johns Hopkins Hospital in Baltimore, writing in a 2021 review:
- Start treatment as soon as possible after the start of initial symptoms to give the best chance of minimizing long-term disability
- Switch therapies promptly when a relapse occurs or MRI shows new neurological damage
- Be aware of any new treatment's mechanism of action -- i.e., how it works on the body. If you're switching because your previous treatment didn't work, you may get better results by trying a treatment with a different mechanism of action.
Which Approach Is More Effective?
Doctors need more research to confirm whether the escalation approach or the early aggressive approach leads to better long-term outcomes for people with MS. The best way for researchers to answer that question is to test the two treatment approaches head-to-head.
Two different groups of scientists are currently doing exactly that. One randomized clinical trial, known as TREAT-MS, is expected to be completed in 2025. The other, known as DELIVER-MS, expects to announce its results in 2026.
But whatever TREAT-MS and DELIVER-MS eventually reveal about effective treatment strategies, patients and doctors should make treatment decisions together.
Read previous installments in this series:
For Your Patients: What to Expect After a Multiple Sclerosis Diagnosis
For Your Patients: What Are the Different Types of MS?
For Your Patients: Coping With the Mental Health Challenges of Multiple Sclerosis
"Medical Journeys" is a set of clinical resources reviewed by doctors, meant for physicians and other healthcare professionals as well as the patients they serve. Each episode of this journey through a disease state contains both a physician guide and a downloadable/printable patient resource. "Medical Journeys" chart a path each step of the way for physicians and patients and provide continual resources and support, as the caregiver team navigates the course of a disease.
