Minimizing the Burden of Treatment in Relapsing Multiple Sclerosis

Yinan Zhang, MD
Ohio State University Wexner Medical Center, Columbus, Ohio

Key Takeaways

  • In addition to efficacy, a range of factors can influence the selection of disease modifying therapies (DMTs) in patients with relapsing multiple sclerosis (MS), including frequency of administration, aversion to needles, and other factors affecting convenience.
  • Patient participation in DMT selection empowers patients to choose the treatment approach that most aligns with their lifestyle, risk tolerance, and efficacy concerns.
  • Shared decision making in choosing a DMT may result in greater adherence and reduced treatment burden in patients with relapsing MS.
  • Even in cases of stable disease and minimal or no MS-related disability, regular follow-up visits with patients taking DMTs are needed to monitor the impact of treatment on safety, quality of life (QOL), and daily functioning.
  • Routinely seeking patient feedback about their satisfaction and concerns regarding their current DMT can help providers identify and address delayed side effects, treatment intolerance, and other factors driving nonadherence.

While the number of available DMTs for patients with relapsing MS has grown substantially, various factors can increase the burden of treatment associated with these therapies. For example, medication tolerability, disease duration, and frequency of administration may influence QOL and, ultimately, treatment adherence in this patient population.1
Yinan Zhang, MD, is the assistant professor of neurology at the Ohio State University (OSU) Wexner Medical Center in Columbus, Ohio. His clinical specialties include MS and related neuroimmunologic diseases, with a particular interest in identifying the optimal treatment approach personalized to each patient. Dr Zhang investigates the impact of aging-related biological changes on disease progression in MS. In this article, he discusses ways in which physicians can help reduce the burden associated with DMTs for patients with relapsing MS.

In a 2022 review by Burtchell et al, patients with MS cited autonomy and convenience of administration as important factors in DMT selection, in addition to safety and efficacy.2 Does this reflect your observations in practice? What specific factors related to medication administration have patients told you were priorities for them?

When it comes to selecting a DMT for MS, there are now over 20 options to choose from. For patients, it can be daunting to distinguish the differences between DMTs in terms of route and frequency of administration, mechanisms, efficacy, side effects, and cost. For many patients, it is easiest to understand the route and frequency of administration.
The other properties of DMTs are harder to understand, such as comparative efficacy between 2 different DMTs. Even for providers, we do not have data on head-to-head comparisons of the different DMTs and often rely on our understanding of the mechanisms of action to approximate efficacy compared with another class of DMTs.
Safety is another concern for many patients. One example is with the risk for progressive multifocal leukoencephalopathy (PML) with natalizumab.3 When patients learn about the association of PML with natalizumab, many will stop considering this drug altogether, even when they test negative for the John Cunningham virus. It is up to the clinician to provide education and reassure patients that, with proper monitoring, we can entirely avoid the devastating side effects of DMTs.
For many patients in my practice, the route and frequency of administration are high priorities for them. In the era of oral DMTs and infusions, many patients are staying away from injectable DMTs, not because of their overall lower efficacy but because of aversion to needles. While oral DMTs can be appealing for their convenience of the route of administration, their daily dosing requirements can be inconvenient for some patients who have busy schedules or are forgetful in taking a daily medication. Infusions are overall infrequent and appealing to many, but for others, the need to take time off from work or travel to an infusion center steers them away from this class of DMTs.

In general, how does the burden of treatment affect treatment adherence in your patients? How do you approach conversations related to potential medication switching to accommodate patient preferences for route of administration?

Treatment adherence is important to prevent new disease activity in MS. Even after a patient has selected their preferred DMT, certain factors may affect their ability to maintain adherence. Side effects are the most common reason for nonadherence. Patients usually inform their providers that experiencing a side effect makes it difficult for them to continue the medication; however, in a few cases, a patient may stop the DMT on their own or take it less frequently due to side effects. Therefore, I always try to schedule a 1-month follow-up visit with a patient starting or switching to a new DMT to make sure things are going well with the new drug.
When a patient informs me of a desire to switch medication due to intolerance or preference for another route of administration, I usually dedicate an entire follow-up appointment to discussing the other options that a patient can switch to. At the OSU MS Center, we also have 2 MS pharmacists to whom we can refer patients for education on DMTs and discussions about choosing a DMT. By spending enough time with patients discussing their options for treatment and answering their questions, we can help them make the best decision and increase the likelihood that they will stay on the new DMT.

Recent findings by Celius et al suggest that patients place greater emphasis on QOL and less emphasis on relapse prevention compared with their physicians.4 Once patients with relapsing MS have initiated a DMT, how can providers be sure to adequately assess for and address treatment-related factors that may affect QOL?

These days, relapses are few and far between for patients who are taking DMTs. Therefore, just as much emphasis should be placed on QOL and the day-to-day experiences of patients taking DMTs. Providers should always ask at each visit how things are going with taking the DMT. Even if, historically, a patient has tolerated the DMT, it is still possible to experience side effects at any point. Side effects may include injection-site reactions, increased risk for infections, lymph node swelling, hepatitis B reactivation, and PML, among other adverse effects.5 Patients may also experience changes in their social situation, such as changing insurance, starting a new job, moving to a new location, or desiring to become pregnant. All of these transitions can affect QOL measures in using DMTs.
It is important to schedule regular follow-up visits, even for patients who are stable and have minimal or even no disability from MS. Anyone taking a DMT should see their MS provider at least every 6 months.5 This allows for monitoring of both the safety parameters and effects of DMTs on QOL. For patients who are beginning to express issues with taking their DMT, it is up to the provider to further explore the cause of these problems and determine after discussing with the patient if the problem warrants a switch in DMT. For example, a patient who has only ever been on an injectable DMT may report injection fatigue but may have gotten used to the discomfort. It is up to the provider to raise awareness for other DMT options, or else the patient may not know that they have the option to switch.

Treatment adherence is important to prevent new disease activity in MS. Even after a patient has selected their preferred DMT, certain factors may affect their ability to maintain adherence. Side effects are the most common reason for nonadherence.

Burtchell et al also found that patients desire information tools, improved communication with providers, and greater involvement in decision making regarding treatment regimens.2 What is the role of shared decision making in reducing perceived treatment burden? What are recommendations for providers to help optimize shared decision making in DMT selection?

When a patient who is already taking a DMT sees me for the first time, I ask how they arrived at selecting this drug for their MS. Often, they reply that their previous provider told them to take it, and sometimes they were not informed of other options. While it may be true that specific MS disease characteristics and patient demographics severely limit the options for DMTs, for the vast majority of patients, there are several options for choosing a DMT.

For patients who are starting DMTs for the first time, providers should spend at least the entire length of a follow-up visit to discuss all of the options for treatment. At OSU, we refer our patients for a visit with our MS pharmacists whenever they are starting a DMT. For practices that do not have this service, the provider should consider scheduling a separate appointment to discuss treatment, which is what we did at my previous practice. For example, for a patient with newly diagnosed MS or for whom a decision is made to start treatment, the patient is scheduled to follow up in 2 weeks to discuss treatment. During this time, their pre-DMT laboratory values would also be available, allowing for a targeted discussion of which options are appropriate and safe.

When patients actively participate in the choice of DMTs, they are empowered to make the best decision that suits their lifestyle, risk tolerance, and desire for efficacy. This reduces treatment burden and promotes greater adherence.6 The extra time spent on DMT education and shared decision making is worth it for everyone.

Possible side effects of DMTs
The use of DMTs may cause side effects such as injection-site reactions, increased risk for infections, lymph node swelling, hepatitis B reactivation, or PML.

What developments are most needed to reduce the non-economic burden associated with currently available DMTs for relapsing MS?

Despite having many options to treat MS, especially compared with only 2 decades ago, there is no perfect DMT. Until we find a cure for MS, DMTs will continue to be used and improved upon to increase safety, reduce side effects, improve convenience of administration, and increase efficacy, especially in the treatment of progressive MS. However, most providers are satisfied with the plethora of options for the treatment of relapsing-remitting MS.
While individually we cannot advance the pace of new drug discovery to improve treatment of MS, we can improve our own practices to reduce the non-economic burden of DMTs for our patients. As mentioned earlier, shared decision making in selecting DMTs and frequent inquiries into the patient’s QOL while using DMTs are important things providers can do to optimize the patient’s experience with DMTs.
When providers spend time discussing treatment options, we empower patients to make informed decisions and minimize problems later on, such as unanticipated side effects and treatment nonadherence. By routinely surveying patient feedback with their current DMTs, we can promptly identify issues such as delayed onset of side effects, signs of DMT intolerance, and reasons for nonadherence. Sometimes when everything is going well, taking a few extra minutes to explain the rationale for treatment, the mechanisms of action for the DMTs, or long-term expectations of treatment will go a long way in making our patients feel like they are in control of their MS.

This Q&A was edited for clarity and length.


1. Kołtuniuk A, Pytel A, Krówczyńska D, Chojdak-Łukasiewicz J. The quality of life and medication adherence in patients with multiple sclerosis—cross-sectional study. Int J Environ Res Public Health. 2022;19(21):14549. doi:10.3390/ijerph192114549
2. Burtchell J, Clemmons D, Clemmons J, et al. A targeted literature search and phenomenological review of perspectives of people with multiple sclerosis and healthcare professionals of the immunology of disease-modifying therapies. Neurol Ther. 2022;11(3):955-979. doi:10.1007/s40120-022-00349-5
3. Berkovich R, Eskenazi J, Yakupova A, Riddle EL. Progressive multifocal leukoencephalopathy risk perception in patients considering natalizumab for multiple sclerosis. Int J MS Care. 2022;24(1):13-17. doi:10.7224/1537-2073.2020-068
4. Celius EG, Thompson H, Pontaga M, et al. Disease progression in multiple sclerosis: a literature review exploring patient perspectives. Patient Prefer Adherence. 2021;15:15-27. doi:10.2147/PPA.S268829
5. Wiendl H, Gold R, Berger T, et al; Multiple Sclerosis Therapy Consensus Group (MSTCG). MSTCG position statement on disease-modifying therapies for multiple sclerosis. Ther Adv Neurol Disord. 2021;14:17562864211039648. doi:10.1177/17562864211039648
6. Ubbink DT, Damman OC, de Jong BA. Shared decision-making in patients with multiple sclerosis. Front Neurol. 2022;13:1063904. doi:10.3389/fneur.2022.1063904
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Reviewed June 2023