Choosing a disease-modifying therapy (DMT) is an important step in managing multiple sclerosis (MS). With over 20 approved treatments now available, the landscape of therapeutic options has expanded significantly.
While this has undoubtedly improved clinical outcomes, it has also introduced increasing complexity into the decision-making process [1.]
Personalised care relies on an ongoing dialogue between the neurologist and the person living with MS, unfolding in three key steps [2.] After the diagnosis, the specialists provide a prognosis, which estimates how the condition will evolve over time. Next, the initial treatment decision is reached by weighing potential risks and benefits, while also accounting for personal factors such as comorbidities, individual preferences, family planning, and risk tolerance. Finally, early response to the chosen treatment is closely monitored, keeping the door open to switch strategies if needed [2.]
What role does risk tolerance play in choosing a therapy?
We ask Professor Daniel Ontaneda of the Cleveland Clinic in Ohio, “One question is how well the person is going to respond to treatment. A separate question is how well the person will tolerate the medication itself. This involves not just safety, but also tolerability. How willing is the person to take a risk? There is a wide spectrum of risk that people are willing to take to keep their MS under control. Some individuals are very risk-adverse and want to take almost no risk, while others are willing to take greater risks as long as their MS is controlled. Every person is different in this regard.”
Risk tolerance is a critical aspect when choosing a treatment plan [3.] A large-scale survey interviewed over 3,000 participants from the North American Research Committee on MS (NARCOMS) [3.] While people with MS viewed with greater tolerance certain side effects, such as infections or thyroid issues, they expressed the least tolerance for severe risk scenarios like kidney injury and progressive multifocal leukoencephalopathy (PML) – a rare brain infection [3.] Fewer than 2% of participants were willing to accept any risk for the benefit of a therapy [3.] The study also observed that men, younger people, and people with higher levels of disability tend to be more tolerant of all risk complications [3.]
“And, of course, this is not solely a patient’s decision.” Professor Ontaneda continues, “It must be balanced against the medical history, which indicates whether the potential risk associated with a specific medication is higher or lower for that individual.”
Anchoring Personalised Care in Diversity
Demographic and environmental factors, combined with clinical features and biomarkers, form the basis for determining the prognosis, which serves as a prediction of how the condition will unfold [3.]
Associate professor Dalia Rotstein of the University of Toronto tells us, “MS can present in different ways in people of diverse racial groups. We know that initial presentations of optic neuritis (inflammation of the optic nerve) and transverse myelitis (inflammation of the spinal cord) are more frequent in Black and Hispanic populations. Furthermore, Black and Hispanic individuals often present with MS at a younger age, exhibit more severe disability at the time of diagnosis, and face a higher risk of earlier disability progression [4.] Research has characterised differences in presentation but also associated biomarkers.”
Biomarkers are key tools for diagnosis, prognosis, and monitoring how the individual responds to treatment [3.] And when it comes to MS, the most important biomarker is, of course, magnetic resonance imaging (MRI).
“We use MRI a lot when selecting treatment because it talks to us about the burden of the disease,” Professor Ontaneda says. “And it’s not only the burden, but also the severity.”
The number of lesions, their location and activity can offer reliable elements to inform the prognosis and the treatment decision [5.] These conventional MRI measures can help identify individuals with high risk of disease progression [5.] Advanced MRI techniques, including the detection of cortical lesions, central vein sign, and chronic active lesions, can contribute to predict long-term outcomes [5.]
Professor Rotstein adds, “Unfortunately, recruitment has been low into clinical trials for people of diverse racial backgrounds. Many of the MS drug trials have enrolled predominantly white individuals, so we still have a lot to learn in that area. Nonetheless, we do have some early findings that can help guide us. We know that a higher lesion load and greater grey matter atrophy are red flags for earlier disability progression and worse outcomes over time. When we look at Black individuals, specifically, we often see, at the time of diagnosis, higher lesion volume and more pronounced atrophy. The literature is more mixed with respect to Hispanic individuals, so further studies are needed. In general, we encourage patients to choose a high efficacy therapy right from disease onset. Having said that, when we see high lesion volumes on an MRI, we are even more motivated to strongly recommend beginning with a high-efficacy approach [6.]”
External factors, such as the specific healthcare system in which an individual operates, must also be considered when choosing a treatment. As Prof. Ontaneda clarifies, “In the United States a major consideration is whether the patient’s insurance will approve a medication. In other countries, clinical guidelines mandate that patients try certain treatments – the so called first-line treatments – before accessing more powerful options. When we speak of personalised medicine, we are integrating all these factors to determine the optimal treatment – not just for the patient, but also for the healthcare system and the clinical realities that neurologists face. Ultimately, we strive to tailor every treatment plan to the unique characteristics of the individual standing in front of us.”
When asked about the future of personalised care, Professor Ontaneda points to a long-held goal, “The MS field has had a dream for many years: to identify genetic markers that can help predict optimal outcomes with specific medications. I believe that probably one day we will find them. It is only a matter of time.”
Written by Stefania de Vito
Special thanks to Prof. Daniel Ontaneda (Cleveland Clinic, Ohio) and to associate Prof. Dalia Rotstein (University of Toronto) for their insights.
References
[1] Tallantyre EC et al Multiple Sclerosis Journal 2026; 13524585261449988.
[2] Rotstein D and Montalban X Nature Reviews Neurology 2019; 15(5): 287-300.
[3] Fox RJ et al Neurology 2019; 92(14): e1634-e1642.
[4] Briggs FBS et al. Multiple Sclerosis Journal 2025; 31(2): 197-206.
[5] Rocca MA et al The Lancet Regional Health–Europe 2024; 44.
[6] Li J et al CNS drugs 2025; 39(9): 823-842.