One of the most common topics that comes up in RMMSC education programs and Q&A sessions is the question of discontinuing disease-modifying therapies (DMTs). Patients want to know when they might consider it, whether it’s safe, and what they can expect if they do.
Early in the disease, many people feel grateful to have medications that help slow progression and fight back against MS. But as the years go by, their circumstances can shift: inflammation often decreases with age, the risk of infections can rise, and the financial and logistical burdens of ongoing treatment become harder to ignore. It’s only natural that patients begin to wonder whether staying on their DMT is still the right choice for them. This growing set of questions led researchers — and the MS community as a whole — to take a closer, more systematic look at when discontinuing therapy may or may not make sense.
Dr. John Corboy, professor emeritus at the University of Colorado School of Medicine and retired Medical Director of the Rocky Mountain MS Center, heard these concerns from his patients and asked a deceptively simple but enormously important question: At what point is it safe for a patient to discontinue their DMT? To answer it, he designed a pioneering large-scale randomized controlled trial involving multiple MS centers across the country. We’ve reported on the results in several webinars and a previous issue of InforMS Magazine (visit MSCenter.org/disco/ for more), but a few key points are worth revisiting here.
The DISCO-MS trial required participants to be 55 years or older, to have had no new relapses for at least 5 years and no new MRI activity for at least 3 years, and to have been on an approved DMT for at least 5 years. The goal was to determine whether stopping DMT under these conditions was non-inferior—in other words, not meaningfully worse—than continuing treatment. Ultimately, the study was not able to demonstrate non-inferiority within the statistical margin required, meaning that the group that stopped medication had a slightly higher chance of new MRI activity than the group that stayed on treatment.
And yet, the trial did something incredibly important: it changed the conversation. For the first time, the MS community — patients and providers alike — had rigorous data to help frame a question that previously relied almost entirely on anecdote and clinician intuition.
The study results also highlight the vital role of shared decision making. Shared decision making happens when clinicians and patients work together to create individualized treatment plans informed by medical evidence as well as the patient’s personal circumstances, preferences, and risk tolerance. The DISCO-MS study reinforces that there is no one-size-fits-all answer to MS treatment. Instead, decisions around continuing or discontinuing DMTs should be thoughtful, collaborative, and tailored to each person’s unique situation.
The DISCO-MS study also inspired additional research.
An interesting study that asked a similar question is the Dutch DOT-MS trial (Discontinuation of Therapy in MS). This study explored whether first-line DMTs could be safely discontinued in people with relapsing-onset MS who had remained inflammatory-stable for at least five years. Unlike DISCO-MS, DOT-MS included younger adults — as young as 18 and on average 10 years younger than in the DISCO-MS trial. The trial was stopped early after a review by its Data and Safety Monitoring Board as those who discontinued their medication had a significantly higher rate of new inflammatory activity than those who continued.
DOT-MS gives clinicians and patients a clear and valuable message: Stopping DMTs at a young age, even after years of stability, carries a meaningful risk of disease reactivation.
There is also another study underway in France that aims to deepen our understanding of this topic in yet another MS population. The STOP-I-SEP trial is evaluating whether people with secondary progressive MS, aged 50 and older, who have had at least three years of clinical and MRI stability, can safely discontinue treatment. This study is ongoing, with results expected in early 2028, and it will add important information for a group of patients who often wonder whether continuing DMTs still provides benefit.
Conclusion
What these studies collectively show is both encouraging and complicated. On one hand, we should celebrate that research is finally asking the questions patients have been asking for years. On the other hand, the answers aren’t simple, and they aren’t the same for everyone.
MS is a complex disease, and the decision to continue or discontinue treatment depends on a mix of age, disease history, risk tolerance, and personal circumstances. The research tells us some things very clearly — such as higher risks for younger adults — but leaves room for interpretation in others.
This is why shared decision making is so essential. When the data doesn’t give us a clean, definitive answer, the path forward is found in thoughtful conversations between patients and their care teams — balancing evidence, experience, and what matters most to each individual.
And perhaps the most hopeful takeaway is this: for the first time, we’re building the evidence base needed to guide these decisions with more confidence and clarity. The questions are finally being asked — and the answers, even when nuanced, are empowering.
