It’s common for people with multiple sclerosis (MS) to switch therapies in the quest to reduce flares and slow the progress of the disease. Each disease-modifying therapy (DMT) comes with its own range of potential benefits and side effects.

Since every person has a unique response to a DMT — and that response can change over time — you may need to reevaluate your MS treatment plan with your healthcare provider at different points in your journey.

Today there are more DMTs available than ever to treat MS, giving people living with the condition many treatment options. Among these choices, certain DMTs have been identified in clinical studies as being highly effective (HE) at slowing disease activity progression compared to other DMTs. Research and clinical practice guidelines now support earlier use of highly effective therapies in many people with relapsing forms of MS.

Increasingly, doctors are recommending HE DMTs as the initial treatment for some people with relapsing forms of MS including relapsing-remitting MS (RRMS), clinically isolated syndrome (CIS), and active secondary progressive multiple sclerosis (SPMS).

Since highly effective DMTs can also carry the risk of serious side effects, it’s important to understand all the risks and benefits involved.

What Makes a DMT Highly Effective?

DMTs reduce the activity of MS by targeting the immune system to reduce its attacks on the central nervous system. MS is considered an autoimmune disease because the body essentially attacks its own nerves and brain cells.

In clinical studies, highly effective DMTs have been shown to better reduce relapse rates and new lesions and slow disability progression compared with older or moderately effective treatments.

Highly effective DMTs for MS span several drug classes, including anti-CD20 monoclonal antibodies (which target certain immune cells) and other monoclonal antibodies. DMTs in different classes work in different ways to slow the progression of MS.

Established Highly Effective DMTs

Many HE DMTs are now approved by the U.S. Food and Drug Administration (FDA). DMTs that have been categorized as highly effective include:

• Alemtuzumab (Lemtrada)
• Natalizumab (Tysabri) and its biosimilar natalizumab-sztn (Tyruko)
• Ocrelizumab (Ocrevus, Ocrevus Zunovo)
• Ofatumumab (Kesimpta)
• Ublituximab (Briumvi)
• Cladribine (Mavenclad)

These therapies have shown strong results in reducing relapse rates, preventing new brain lesions, and slowing disability progression in relapsing forms of MS.

Measurements of Effectiveness

Measuring effectiveness is important because it helps physicians know if a treatment option is working. It also helps classify different prescriptions as being moderately effective, highly effective, etc.

But how is effectiveness measured? Briefly, doctors monitor the effectiveness of an MS treatment several ways. A doctor’s recommendations on whether to continue or switch medications are mostly based on:

• MRI results and lab tests that measure MS disease progression by analyzing lesions in the brain and spinal cord
• The frequency of MS relapses (also called disease flares or MS episodes)
• How disability progresses over time
• Factors such as pregnancy, comorbidities, or side effects

Because your doctor understands how your MS has progressed and how you’ve responded to DMTs, they can recommend the most effective therapy for you if you decide to switch.

The Benefits of Starting a Highly Effective DMT Early

There is increasing evidence that the earlier someone with MS starts highly effective DMT treatment, the better the disease course will look. Research has shown that people who begin treatment with an HE DMT are more likely to reach a state called “no evidence of disease activity” (NEDA). The concept of NEDA evolves depending on the parameters used but reaching NEDA basically means that the available markers for disease monitoring show there is no active disease.

The earlier someone with MS starts highly effective DMT treatment, the better chance they have to effectively slow their MS progression.

In one study, 68 percent of people who started a highly effective DMT achieved NEDA — defined as a lack of relapses, no new MRI lesions, and no disease progression — after 12 months. About 52 percent of these people still had NEDA after 24 months. These results were better than those seen in people who started with a moderate-efficacy therapy instead.

However, your neurologist may not recommend starting an HE DMT right away because of concerns about side effects or if your disease appears mild.

Side Effects of Highly Effective DMTs

Unfortunately, highly effective DMTs can sometimes carry a risk of serious side effects. It’s important to note that some of these side effects occur very rarely. Additionally, each individual’s risk varies based on their medical history, inherited factors, and overall health. Your doctor is the best person to help you assess your personal risk for each side effect.

Serious side effects of highly effective DMTs may include:

• Heart problems
• Opportunistic infections — Infections that occur more often and are more severe in people with weakened immune systems
• Cancer
• Eye disease
• Progressive multifocal leukoencephalopathy (PML) — A serious brain disease caused by a viral infection
• Stroke
• Secondary autoimmune disorders
• Cryptococcal meningitis

Risk for each side effect differs by drug. For example, alemtuzumab is known to cause thyroid problems, among other possible side effects. On the other hand, natalizumab is associated with PML in people who test positive for John Cunningham virus.

Weighing Risks and Benefits of Highly Effective DMTs

Like all medications, highly effective DMTs have both risks and benefits. Safety concerns should be a key consideration when thinking about switching therapies. Also, an individual’s safety profile may change as they age, develop other health conditions, or experience immune system changes. Researchers have found that the safety risks of certain MS medications are likely to be greater as people age.

However, these risks must be carefully weighed against the benefit of reductions in the relapse rate and progression of MS. As immune cells attack the myelin of the brain and spinal cord, new lesions form and may result in worsening MS symptoms, more exacerbations, and disability progression. Treating early with HE DMTs may help limit this damage.

Through shared decision-making, you and your doctor will discuss these risks and benefits. Your role is to share your goals, preferences, and priorities for the doctor to take into account.

Your neurologist will help you weigh the possible side effects of a highly effective DMT against the potential benefit of reduced relapse rate and slower progression of MS.

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