How do doctors choose an MS medication?
There are now over a dozen disease-modifying therapies (DMT) available to treat multiple sclerosis. All of these medications reduce the frequency of MS relapses and the number of inflammatory lesions in the brain; most also appear to slow the rate of disability. But with so many drugs to choose from, how does a doctor select the best option to control your MS?
For people with relapsing-remitting MS, the first consideration for doctors is the severity of MS: how often there are relapses, how many lesions are visible on the MRI (as well as their size and location), whether relapses have left persistent impairments, and whether the person’s symptoms are especially worrisome. Doctors will also consider if MS is quickly getting worse, e.g. the distance a person can walk without difficulty has shortened considerably over the past year.
Secondly, doctors will look at whether there are certain risk factors for a worse course of disease. Males, individuals of non-white race, and people who develop MS at an older age are most at risk. Lifestyle and some medical conditions can also influence how a person does over the course of their MS, but these factors are probably related more to their general unwellness (e.g. smoking, obesity, lack of exercise) rather than directly related to the disease process itself (Tettey and colleagues. Neuroepidemiology 2016;46:106-113).
Despite the many known risk factors, it is very difficult to predict from the outset who will have a favourable disease course and who will develop severe disability. So this usually requires a trial-and-error approach to treatment: a medication is started with the view to continuing it long-term, but with a Plan B in place to switch treatments if there is ongoing disease activity. A new treatment may be indicated if the person on a treatment is continuing to have relapses or has new lesions on their MRI.
Most people newly diagnosed with MS do not have highly active or worrisome disease. So doctors typically opt for one of the oral medications (Tecfidera, Vumerity or Aubagio) or, less commonly, one of the injectable drugs (Copaxone, Avonex, Betaseron/Extavia, Rebif or Plegridy) (Kantor and colleagues. Clin Ther 2020;42:2136-2147.e3). All of these medications reduce the frequency of relapses, and many people find they can remain on treatment for years without too many problems. For example, a long-term study of Tecfidera reported that relapses were uncommon and 73% of people showed no worsening of their disability over a 9-year course of treatment (Gold and colleagues. Ther Adv Neurol Disord 2020;13:1756286420915005). Similarly, long-term studies of Aubagio have found that over 50% of people do not have worsening disability for up to 9 years (Miller AE. Ther Adv Neurol Disord 2017;10:381-396).
A doctor’s choice of starting therapy will be influenced by the person’s preferences. Some people like taking an oral medication; others would prefer to have injections. Some like to schedule their treatment at the same time each day; others prefer less frequent dosing (e.g. once a week or twice a month). If a woman is planning to become pregnant in the near future, that will also influence the choice of treatment.
About 10% of people with MS have very active disease from the outset, and they will generally require a more potent therapy from the start. These more potent medications include Gilenya, Zeposia, Mavenclad, Ocrevus, Kesimpta and Lemtrada. These treatments are generally more effective at reducing relapses. The trade-off is a risk of more serious side effects. For some, the potential benefits of controlling severe MS are worth the risk of developing side effects. So it is important to have this conversation about the possible benefits and risks with your neurologist.
In recent years, there has been a trend toward a more aggressive treatment approach even in people with less active disease. The thinking is that more complete suppression of inflammation will have added benefits in the long term. In this scenario, the assessment of benefits and risks will be slightly different and will require a thorough discussion with your healthcare team.
The decision to use one of these medications will depend in part on a person’s risk tolerance (Maurino and colleagues. Patient 2021;14:241-248). Some people see MS as the greater threat and want to suppress their MS with the biggest gun in the arsenal. Other people prefer a more conservative approach because they are concerned about the risks of treatment (Rotstein and colleagues. Nat Rev Neurol 2019;15:287-300).
When arriving at the choice of treatment, there is no right or wrong answer. The selection of the best medication is very much a collaboration between you and your doctor. Your doctor will offer his/her expert opinion about the state of your MS and will suggest a few treatment options. It will then be up to you to inform your doctor about the regimen that you can most easily accommodate in your daily life, the level of treatment-related risks you are comfortable with, and how aggressively you want to treat your MS. This collaborative approach helps to ensure that your MS medication will be the best option for you – tailored to your illness and most suited to your individual preferences.
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