Understanding Patient Preferences in the Treatment of Multiple Sclerosis: The Need for Switching Disease-Modifying Therapies

May Han, MD, is an associate professor of neurology and neurological sciences at Stanford University School of Medicine, in California. She also is a board-certified neurologist and clinician-scientist who specializes in multiple sclerosis and central nervous system demyelinating diseases. Her research focuses on utilizing a systems biology approach (eg, genomics, transcriptomics, and proteomics) to identify targets for therapy in MS and neuromyelitis optica. Dr. Han is an attending physician at the Stanford Neuroscience Health Center’s Neuro-Immunology Clinic and at Stanford Hospital in California.

In patients with MS, DMTs have been shown to reduce the frequency and severity of relapses. They also can reduce the development of new lesions in the brain and spinal cord and slow the development of disabilities associated with MS. With DMTs, is there a standard protocol that patients initially receive, or is treatment more individualized to the patient?

We do know that early initiation of a DMT decreases the relapse rate and can prevent  progression of the disabilities associated with MS.¹ As to how therapy is selected, we first determine what type of MS a patient has. We then clinically characterize the phenotype and narrow down our treatment choices to a suitable medication with which to begin therapy. But, as there is a growing number of medications now available for relapsing-remitting MS, choosing the most appropriate drug for an individual can be challenging.

While we do not have a treatment algorithm recommended to us by the US Food and Drug Administration (FDA), we do have guidelines. We look at 3 factors: disease activity, size, and location of visible lesions on the magnetic resonance imaging (including evidence of spinal cord or optic nerve involvement), and lesion activity (all active, active and chronic, or just chronic). We also determine if the patient has 1 or 2 lesions or if the lesions have been progressing for a while. Based on these factors, we decide if the patient is appropriate for treatment with a DMT as first line therapy.

Clinicians typically opt for an oral medication or, less commonly, an injectable drug. Studies have shown that patients who were on oral medications were less likely to relapse.² Oral medications, such as teriflunomide and dimethyl fumarate, reduce the frequency of relapse and many patients find that they can remain on these medications for years due to the drugs’ tolerability and fewer severe adverse events.^3,4

However, if the patient has highly active disease and other risk factors for poor outcomes, such as older age, male gender, spinal cord involvement, and other comorbidities, we may opt for a high-efficacy therapy such as ofatumumab or cladribine. Importantly, all of these drugs have safety risks, so we don’t want to overtreat the disease, but we also don’t want to undertreat it. We want the treatment to be efficacious enough for the level of disease activity in the patient. Studies focusing on patients with relapsing-remitting disease show that patients who are placed on high-efficacy therapies early on benefit from this initial aggressive therapy.⁵

The patient’s treatment preference is important because we want the patient to be able to live his or her life rather than be consumed by therapies and the disease. Some people do not mind getting injections and others just can’t do it. Some patients prefer oral medications, but others often forget to take their pills. Fear of disability and impact on lifestyle can drive some patients’ desire for a high-efficacy DMT despite the success of their current treatment.⁶ Patient preferences and behaviors certainly must be considered in treatment decisions.

Another key issue in choosing treatment is the financial burden on the patient due to the cost of the drugs, which have steadily increased over the years.^7,8 Drugs to treat MS are expensive in the United States and insurance coverage varies based on factors such as drug cost and the patient’s co-pay. If a drug costs $300 a month out of pocket, for example, and the patient cannot afford it, then treatment adherence will be an issue. So then we must go with the next best option, because at the end of the day, the treatment has to be something that is affordable to the patient since they may be on this drug for a long time.

As you can see, choosing the right drug is an art in itself. Ideally, we would like to do genetic testing and use biomarkers, as is done in determining treatment strategies for cancer, but we do not yet have that information for MS. That is a focal point of my research now.

Individual response to existing therapies for MS varies among patients as does the risk of adverse events. When should switching DMTs be considered and are there any formal guidelines for doing so?

There are no clearly defined guidelines on switching DMTs, and the decision to do so should be a collaborative one between the clinician and patient. We have to take into consideration a variety of factors, including goals of treatment, disease activity, medication history, and personal preferences. One of the main reasons to switch a medication is if the patient is having either clinical or radiographic breakthrough relapses. Some patients with relapsing-remitting MS experience disease progression so in these cases, the therapy should be changed.

There also are specific circumstances for changing therapy. For example, a patient may have tolerated natalizumab very well but now shows antibodies for anti-John Cunningham virus in serum, which means an increased risk of developing progressive multifocal leukoencephalopathy.⁹ Other examples are B cell-depleting therapies, such as ocrelizumab, which, while convenient for some patients because it’s given via infusion twice a year, can place patients at a higher risk of infection, especially in patients with known risk factors. This in turn raised concerns during the pandemic about the potential risks of the COVID-19 virus on patient with MS who were receiving immunotherapy.¹⁰ The immune response to the COVID-19 vaccine also may be blunted due to the patient being immunocompromised.

As MS most often develops in young adults, pregnancy also is a factor for consideration. Most medications that are used to treat MS symptoms are not compatible with pregnancy. Therefore, treatment is generally stopped, and steroids are used to manage relapses during pregnancy.

So, from the physician’s perspective, a switch in medication becomes essential when the therapy is not managing the disease activity, when the patient is experiencing relapses or regressing, or when the patient is not tolerating side effects.

For patients, often the first reason for wanting to switch therapies is intolerance to a medication. While we consider some drugs to be well-tolerated, many patients never get used to the side effects. The second reason for wanting to switch is difficulty with adhering to a therapy’s administration. Some patients can never remember to take their evening pill or are unable to give themselves an injection. The third reason for wanting to switch is due to a change in the patient’s insurance coverage and the cost of treatment has increased. In these cases, we may need to use a generic version of a drug. The last most common reason for the desire to switch is lifestyle. In some cases, patients prefer to just get an infusion once a month or every 6 months and then not have to worry about it. Studies also suggest that patients have a higher preference for therapies that improve their symptoms and delay progression over those that decrease relapse rates.¹¹ The frequency of dosing also has been identified as equally important as a therapy’s efficacy and safety.¹²

Patient preferences in desiring to switch therapies (as opposed to switching due to clinician-assessed efficacy) may include the therapy’s route of administration and side effect profile, among other concerns. Patients also may place a higher value on certain efficacy endpoints, such as effects on quality of life. How much input does the patient have in the treatment decision?

It is a joint decision between the clinician and patient, and how much trust the patient has in the clinician plays a role in this joint decision making. Most of my patients want to stay with me as their clinician because of this partnership. I give my patients the best possible information that I can, based on the evidence, and I give them the tools they need to make their decisions.
Sometimes they may be hesitant and feel uncomfortable about a therapy’s potential side effects, for example, and in these cases, I give them the best explanation I can, backed by scientific evidence. But, at the end of the day, it is their body and they need to be comfortable with the treatment decisions. As their clinician, it is my role to support them while determining the best course of therapy.

Ofatumumab is administered as a once-monthly subcutaneous injection while teriflunomide is taken orally as a once-daily tablet. In your experience, what attributes of DMTs are most important to patients that should be included in treatment decisions? Do you find that patient decisions typically lean more towards ease in route of administration or ease in dosing frequency?

Every patient is different. Some do not mind taking an oral drug every day and would in fact prefer that over an injection, while others would prefer the injection once a month. The ease at which a therapy works for a patient might be different for another. I have found that the least preferred regimen was subcutaneous injections 3 times weekly. A sample study found that intravenous infusions given 3 or less times per year was the preferred regimen, while self-injection 1 to 3 times per week was the least preferred treatment option.¹³

In your experience, does patient preference in the selection of DMT typically have an
effect on medication adherence?

Absolutely and sometimes a patient will start on a therapy that they had doubts about only to discover their fears were unfounded. For example, after getting 1 or 2 infusions, they may feel that infusion therapy is not a huge deal. Some patients get over their fear of injections to find out it’s their preferred route of administration. Sometimes, the opposite occurs. The patient may have thought an infusion would be easy but learns they aren’t able to tolerate the side effects. All patients respond to therapies differently and that’s why we sometimes need to switch medications — to find the therapy that is most effective and comfortable for the patient so they are able to adhere to the treatment regimen.

This Q&A was edited for clarity and length.