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Continued monitoring and care needed when older patients with MS stop DMT

By Jake Remaly

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Whether to stop disease-modifying therapy (DMT) in older patients with multiple sclerosis (MS) can be a fraught topic. Guidelines acknowledge that there are limited data to guide the decision and suggest that clinicians and patients can make this call together. While some patients welcome the prospect of not having to pay for or take medication anymore, others are “anxious” when the topic comes up, said Le Hua, MD, of the Lou Ruvo Center for Brain Health at the Cleveland Clinic in Las Vegas. She tells nervous patients, “If it scares you to come off medication, then stay on it.”


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Discontinuing DMT may allow patients to avoid side effects and travel without refrigerating drugs or bringing needles through the Transportation Security Administration. In some cases, patients who have discontinued therapy resist resuming DMT when follow-up monitoring detects a lesion on MRI because they enjoy the freedom from DMTs, Dr. Hua said.

Dr. Hua and colleagues studied data from 600 patients at Cleveland Clinic MS specialty clinics who were aged 60 years or older and had been on DMT for more than 2 years (Mult Scler. 2019 Apr;25[5]:699-708). About 30% discontinued DMT. Among patients who discontinued, one had a clinical relapse, and a few had MRI changes. In all, 10.7% who stopped treatment-reinitiated DMT, the researchers reported in the Multiple Sclerosis Journal. When DMT discontinuation was initiated by a clinician, patients were less likely to restart therapy, compared with when discontinuation was initiated by a patient.

The data also indicate that the majority of older patients stay on treatment. At Cleveland Clinic, clinicians ask patients how things are going with their DMT. If the patient is aged 60 years or older and they have concerns about side effects or tolerability, the clinician raises the possibility stopping DMT.

Dr. Le Hua

Guidelines emphasize choice and follow-up

Studies of outcomes after stopping DMTs in various patient subgroups are limited, according to a 2018 American Academy of Neurology practice guideline on DMTs for adults with MS. “More studies are needed to inform decisions about the possibility of DMT discontinuation, particularly concerning when there is a high risk of relapse or disability after DMT discontinuation, and in which circumstance, if any, discontinuation poses little or no harm,” the guideline says. “People with MS who are stable on DMTs may question the continued value of using DMTs. If people with MS on DMTs stop these medications, continued monitoring may show subclinical disease activity or relapse activity that would indicate a possible need for treatment resumption. … People with MS who are on DMTs with no evidence of ongoing disease activity may be benefiting from their DMT with disease suppression. There are presently no biological markers of medication efficacy that can guide decision making in this area.”

The guideline suggests that for patients with relapsing MS who are stable on DMT and want to discontinue therapy, clinicians should counsel them about the need for ongoing follow-up and periodic reevaluation of the decision to discontinue DMT (level B evidence). In addition, “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 (level B),” according to the guideline.

For patients with secondary progressive MS, clinicians should “assess the likelihood of future relapse” (level B) and “may advise discontinuation” of treatment in patients with secondary progressive MS who do not have ongoing relapses or gadolinium-enhancing lesions on MRI and who have not been ambulatory for 2 or more years (level C). For patients with clinically isolated syndrome, “clinicians should review risks of stopping and continuing” therapy (level B), the guideline says.

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Brain Health: Time Matters in Multiple Sclerosis,” a report endorsed by dozens of MS groups, advises clinicians to “maintain treatment with a disease-modifying therapy for as long as a person with MS would be at risk of inflammatory disease activity if they were not receiving treatment.” The European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) and the European Academy of Neurology (EAN) jointly released a guideline that suggests neurologists consider continuing DMT in patients with relapsing remitting MS who are stable and do not have safety or tolerability concerns.

“The majority of currently available practice guidelines on discontinuation of DMTs advocate the central importance of patient choice in the decision-making process, supporting the ethical principle of respect for patient autonomy,” according to a review by Knox et al. that examined guidelines from British and Canadian groups, as well as from ECTRIMS, EAN, and AAN (Int J MS Care. 2019 May 22. doi: 10.7224/1537-2073.2018-107). “In the absence of strong evidence on when to discontinue DMTs, shared decision making and consideration of the ethical complexities may assist the decision-making process and guide future research directions.”

When participants were asked if their disease was nonactive, would they consider stopping their DMT, only 11.9% stated they were likely or very likely” to consider discontinuation.

Trial may clarify contentious issue

“Whether and when to discontinue DMTs in stable patients are highly contentious issues with no high-quality evidence to guide decision making,” John R. Corboy, MD, and colleagues wrote in a commentary on the AAN guideline. “The guideline suggests considering DMT discontinuation in some patients with [clinically isolated syndrome] or early [relapsing remitting] MS who are doing well. This is somewhat counterintuitive, as stabilization is the main goal of therapy. However, patients with a favorable prognostic profile, or whose disease may have become quiescent with increasing age, might be reasonably observed off treatment and monitored for recurrent disease activity. This approach potentially may permit discontinuation of expensive, intrusive, and possibly unnecessary treatments.”

Dr. John R. Corboy

The risk-benefit analysis of DMTs for MS may change over time, Dr. Corboy said. He is codirector of the Rocky Mountain Multiple Sclerosis Center at Anschutz Medical Campus and professor of neurology at University of Colorado at Denver, Aurora.

“The nature of MS changes as the patient ages, both clinically and pathologically,” he said. “While presently available disease-modifying therapies have great utility in many patients, the benefits appear greatest in those who are young and have ongoing active inflammatory disease as manifested by acute relapses and new/active MRI lesions. In addition, risks of DMTs may increase with age and increased comorbidities, and the costs of DMTs are very high for the patient and society. Thus, whether presently available DMTs are useful in MS as people age, and whether it is safe to consider a trial off DMT, are very important questions.”

To that end, Dr. Corboy is principal investigator for the DISCOMS (Discontinuation of DMTs in MS) trial, which recently closed enrollment at 260 patients. This randomized, controlled trial of DMT discontinuation, funded by the Patient-Centered Outcomes Research Institute (PCORI) and the National Multiple Sclerosis Society (NMSS), included patients aged 55 years and older who have not had a relapse for at least 5 years and have not had a change on MRI for at least 3 years.

Patients will continue or stop treatment, and investigators are blinded to whether the patient is taking a DMT assess patients for 2 years. The primary outcome is new relapse or MRI lesion. Secondary outcomes include disability progression and patient-reported measures.

“Outside of the study funded by PCORI and the NMSS, I have personally removed more than 150 patients from DMT in roughly the same context as those in the trial, i.e., 55-plus in age with stability for several years while on a standard DMT,” Dr. Corboy said. “The vast majority have done well with several years of follow-up, but there have been a small number who have recurrent clinical or radiographic disease, including at least one in their 70s.”

In practice, Dr. Corboy discusses the issue with patients and hears their perspective.

“I … tell them what is known and what is unknown, describe potential risks and benefits to being off DMT [and staying on], and assess their view of how to proceed,” he said. “Many patients have fairly distinct views … and we typically go with their wishes. Some change their mind after the discussion, and some change their mind later, in both directions.”

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“We want to look at the whole patient, things driving their symptoms – pain, fatigue, and walking difficulty.”

Patients value evidence

Marisa P. McGinley, DO, conducted a study with Dr. Corboy and colleagues to examine how patients view the concept of discontinuing therapy. In focus groups, patients with MS expressed “overarching concern about stopping medication” that may be working as intended, said Dr. McGinley, a neurologist at the Cleveland Clinic’s Mellen Center for MS Treatment and Research. A representative quote: “If it ain’t broke, don’t fix it.”

Another theme from the focus groups was that patients value insights and guidance from clinicians, as well as scientific evidence.

Dr. McGinley and colleagues created a survey based on the focus group discussions that they sent to 1,000 people in the North American Research Committee on MS (NARCOMS) registry. Survey recipients were aged 45 years or older and had been on their most recent DMT for at least 5 years. In all, 377 surveys were completed. About 60% of the participants “indicated they thought their disease was ‘nonactive,’ ” the researchers reported in Multiple Sclerosis Journal (Mult Scler. 2019 Aug 1. doi: 10.1177/1352458519867314). “When participants were asked if their disease was nonactive, would they consider stopping their DMT, only 11.9% stated they were likely or very likely” to consider discontinuation. Participants said the most important reason to stop medication would be safety, followed by continued disease progression on medication and physician recommendation.

One neurologist’s experience

Drug costs, side effects, or lack of perceived efficacy may motivate patients with MS to consider stopping DMT, according to Gary Birnbaum, MD. For their part, clinicians might be motivated to discontinue a patient’s DMT because of a lack of efficacy or increased risk of toxicity and side effects in older individuals, as well as cost, said Dr. Birnbaum, emeritus professor of neurology at University of Minnesota, Minneapolis, and director of the MS Treatment and Research Center (retired) of the Minneapolis Clinic of Neurology.

In 2017, Dr. Birnbaum described the experience of patients with MS under his care who had stopped DMT on his recommendation (Int J MS Care. 2017 Jan-Feb;19[1]:11-4). Dr. Birnbaum examined data from 77 patients who previously had relapsing MS but no evidence of acute CNS inflammation for at least 2 years and who had been advised to stop DMT. He also examined data from another group of 17 individuals with relapsing MS who had stopped DMT for other reasons, including 16 who stopped treatment on their own and 1 who lost insurance. None of the 94 patients had been receiving oral or intravenous DMTs. Dr. Birnbaum examined clinical and CNS imaging for at least 1 year after patients stopped therapy.

Among the patients advised to discontinue treatment, 11.7% had recurrence of acute disease, compared with 58.5% of those who stopped DMT for other reasons. Almost all instances of disease recurrence occurred within 2 years of stopping treatment. “All patients with recurrent disease were offered the opportunity to restart DMT, and almost all did,” Dr. Birnbaum reported in the International Journal of MS Care.

Patients who stopped treatment on their own or because of loss of insurance were significantly younger, compared with patients who were advised to stop (median age, 49 years vs. 61 years). Among those advised to stop therapy, patients who remained stable had a median age of 61 years, whereas those who worsened clinically or on MRI had a median age of 56 years. “These findings suggest that older individuals, in their seventh or greater decades of life, with no clinical or MRI evidence of [relapsing MS] for 2 years or more can safely stop DMT with an almost 90% chance of nonrecurrence of acute inflammation,” he wrote.

Some patients not included in the study opted to continue therapy despite Dr. Birnbaum’s recommendation to discontinue. Some wanted to avoid the potential risk of recurrent disease, and some wanted “to feel active and empowered in controlling their illness,” Dr. Birnbaum noted.

His experience may help delineate which patients are candidates to stop therapy. “DMTs can be safely stopped in older individuals with stable or progressive MS with no evidence of acute or active CNS inflammation for at least the prior 3-5 years, though careful follow-up for at least 2 years thereafter, including CNS MRIs, is necessary,” Dr. Birnbaum said.

Symptomatic treatment does not stop

After patients discontinue DMT, Dr. Hua monitors them by MRI 6 months later and every year after that. At the Cleveland Clinic, clinicians also assess patients’ motor, visual, and cognitive performance. If those measures indicate sudden decline after stopping therapy, that could be an indication to resume DMT, Dr. Hua said.

And although patients may stop DMT, other treatments continue. “We want to look at the whole patient, things driving their symptoms – pain, fatigue, and walking difficulty,” she said. If patients are weaker and less mobile, physical therapy may help recondition them. Medications that treat spasticity may make it easier to move. Treating bladder problems can improve quality of life. Addressing these symptoms, according to Dr. Hua, is “as essential as DMT itself.”

Dr. Gary Birnbaum