A significant portion of patients with multiple sclerosis (MS) can achieve a stable disease state when treated with modern disease-modifying therapy (DMT), especially when started early in the disease course, begging the question — can these medications be stopped?
Research into the safety of stopping DMT in patients with stable MS has yielded mixed results.
Whether DMT can be safely stopped and when has it become a “hot topic.” This is a rich area of study,” Le Hua, MD, director of the Mellen Program for Multiple Sclerosis, Cleveland Clinic Nevada, Las Vegas, told Medscape Medical News.
“Currently, there are no specific guidelines on what to do with regards to stopping therapies. Right now, this is a decision between the individual patient and provider,” said Sammita Satyanarayan, MD, with the CGD Center for Multiple Sclerosis, Department of Neurology, Mount Sinai Hospital, New York City.
How Frequently Are DMTs Stopped and Why?
Research suggests that up to 20% of patients with long-term stable MS may consider or attempt to discontinue DMT — for various reasons.
Long-term disease inactivity can lead patients and clinicians to question the need for ongoing therapy. Tolerability issues and adverse effects, including but not limited to, injection site reactions, infections, fatigue, and gastrointestinal issues may also fuel a desire to stop.
In addition, serious risks — such as progressive multifocal leukoencephalopathy associated with natalizumab — can significantly influence the decision to discontinue treatment. Many patients prioritize quality of life over the potential long-term benefits of therapy, especially when the treatment adversely affects their daily lives.
High out-of-pocket costs, lack of insurance coverage, or logistical difficulties in obtaining or administering DMT may also play a role, especially in countries with limited healthcare access.
Older adults, in particular, may discontinue DMT due to other comorbid health conditions, reduced disease activity in later years, or concerns about medication interactions.
What Does the Research Show?
Research on the safety of discontinuing DMTs in stable MS has produced mixed results. Outcomes of discontinuation may vary based on individual patient factors including age, duration of stability, and the type of MS.
The DISCOMS trial— the first randomized trial to examine whether older adults with MS can safely discontinue DMT after years of being relapse-free — failed to deliver a definitive conclusion.
The noninferiority trial included 259 patients aged 55 years or older (mean age, 63 years) from 20 US centers. Study criteria at baseline included no changes in patient brain lesions on MRI for at least 3 years and no relapses for at least 5 years. The primary outcome was the development of new brain lesions or worsening on the expanded disability status scale (EDSS).
With an average follow-up time of about 2 years, approximately 5% of patients who continued DMT had new disease activity compared with 13% of those who stopped treatment. However, there was no significant difference between groups in relapse or disability progression, as previously reported by Medscape Medical News.
Notably, the numbers of specific events were small; only one patient in the drug continuation group experienced a relapse compared with three patients in the discontinuation group, the DISCOMS study investigators reported.
Therefore, DMT discontinuation “might be a reasonable option in patients older than 55 years who have stable MS but might be associated with a small increased risk of new MRI activity,” they concluded.
Another randomized controlled discontinuation trial known as DOT-MS enrolled 89 patients aged 18 years or older with stable MS for over 5 years. In this study, about 18% of patients who went off DMT experienced inflammatory disease activity recurrence compared with none in those who continued DMT, which led to early termination of the trial.
A separate study showed no significant difference in clinical outcomes in patients with stable MS older than 60 years who discontinued DMT vs in those who continued therapy.
The STOP-I-SEP randomized controlled trial underway in France is further exploring the safety of stopping DMT in stable MS.
Let Age Guide Decisions?
Age appears to be a critical factor when considering stopping DMT for MS in a stable patient, experts who spoke with Medscape Medical News emphasized.
“Based on several real-world studies, it seems like age is probably a better predictor of success of stopping therapy than the duration of disease stability. The overall theme seems to be — the older you are, the more successful we are in stopping therapy. Age 60 is probably the safest age cutoff that we have for now but there will always be individual patient factors,” Hua noted.
In Hua’s opinion, age is the most important guiding factor, whether or not to even discuss stopping.
“If someone is in their 40s or 50s, and they want to stop medication, the answer is going to be no, but what we might want to do is switch their medication if it’s not working or there are complications from the therapy,” Hua shared.
Patricia Coyle, MD, neurologist and director of the Multiple Sclerosis Comprehensive Care Center, Stony Brook University Medical Center, Stony Brook, New York, agreed that age is the critical factor when considering discontinuing treatment.
“I think the older you are, if you are stable and you’ve remained with relapsing MS, many of those patients probably don’t need to be on treatment. So I will spontaneously bring this up in any patient over age 70-75 because if they have remained stable at that age, I think there’s a good chance they will remain stable. I think as you go down in age, it becomes iffy,” Coyle told Medscape Medical News.
“I personally think age 55 is too young. I would be reluctant to withdraw treatment in somebody at that age who was stable, unless we get better data. As they get up to 60 and 65, I would start to feel more comfortable. But still, if they’re not being harmed by the treatment, I would be most confident in those age 70-75 or older,” Coyle added.
Satyanarayan believed “there may definitely be a group of people for whom this is safe but we need some more work to figure this out and predict who that will be. I do hope in the next 10-20 years, I will have more information on how to safely discontinue therapies for folks.”
For now, Satyanarayan said it’s an option that she would “only consider in patients who had been very stable for many years, who are older, and particularly in patients who have had very mild symptoms/injury from their disease.”
She would also consider stopping DMT if a patient is incurring too many adverse effects (infections, etc.) from the medication or has progressive MS and they are continuing to progress despite having tried the few therapies approved for progressive MS — “in which case the pros of treatment would no longer outweigh the risks.”
What Do the Guidelines Actually Say?
The American Academy of Neurology (AAN) 2018 recommendations offer the following advice:
- In people with relapsing-remitting MS who are stable on DMT and want to discontinue therapy, clinicians should counsel people regarding the need for ongoing follow-up and periodic reevaluation of the decision to discontinue DMT.
- Clinicians should advocate that people with MS who are stable (that is, no relapses, no disability progression, stable imaging) on DMT should continue their current DMT unless the patient and physician decide a trial off therapy is warranted.
- Clinicians should assess the likelihood of future relapse in individuals with SPMS by assessing patient age, disease duration, relapse history, and MRI-detected activity (eg, frequency, severity, time since most recent relapse or gadolinium-enhanced lesions).
- Clinicians may advise discontinuation of DMT in people with secondary progressive MS (SPMS) who do not have ongoing relapses (or gadolinium-enhanced lesions on MRI activity) and have not been ambulatory (EDSS ≥ 7) for at least 2 years.
- Clinicians should review the associated risks of continuing DMTs vs those of stopping DMTs in people with clinically isolated syndrome using DMTs who have not been diagnosed with MS.
What About DMT Use During Pregnancy?
The decision to stop or continue DMT during pregnancy is complex and must balance the risks for maternal disease activity with the safety of the medication for the developing fetus.
Pregnancy often has a protective effect against MS relapses, particularly in the second and third trimesters, due to hormonal and immunological changes. However, the postpartum period carries a heightened risk for relapse, particularly within the first 3 months after delivery.
In general, current AAN guidelines recommend discussing pregnancy with women with MS before initiating DMT as “part of good clinical practice.”
They advise monitoring the reproductive plans of women with MS and discuss the reproductive risks and use of birth control during DMT in women of childbearing potential who have MS.
Women with MS should be counseled to stop their DMT before conception (and stop it if accidental exposure during pregnancy occurs) unless the risk for disease activity during pregnancy outweighs the risk associated with the specific DMT during pregnancy.
DMT should not be started during pregnancy unless the risk for MS activity during pregnancy outweighs the risks for specific DMT use during pregnancy. DMTs vary in terms of risk to the fetus, so the choice may be influenced by plans for pregnancy, the guidelines state.
Hua, Coyle, and Satyanarayan had no relevant conflicts of interest.
Source link : https://www.medscape.com/viewarticle/stop-disease-modifying-therapy-stable-ms-yes-or-no-2025a10001sw?src=rss
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Publish date : 2025-01-24 11:15:00
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