Can Some Patients with Multiple Sclerosis Stop Treatment?

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New Orleans, LA—Patients with multiple sclerosis (MS) often spend a lifetime using disease-modifying therapy (DMT). Some experts are now wondering whether some of these patients can discontinue treatment without increasing the risk for disease relapse.

Researchers from the University of British Columbia, Vancouver, questioned whether there are subsets of patients who can safely stop therapy. Although DMT clearly does modify relapse rates and progression of disability early in patients with relapsing-remitting MS (RRMS), it remains unknown whether their efficacy continues late in the disease course or in secondary progressive MS, said Devyn Parsons, BSc, Medical Student, University of British Columbia, Vancouver, Canada, at the 2017 Annual Meeting of the Consortium of Multiple Sclerosis Centers.

Ms Parsons and colleagues reviewed the MS literature through 2017 and found no randomized controlled trials that addressed the question of treatment discontinuation, but they identified 6 observational studies. Their analysis led to their conclusion that it is reasonable for clinicians to have a conversation about DMT discontinuation in some patients.

However, Ms Parsons cautioned against being overly confident in this approach. “It would be a mistake at this point to tell a patient, ‘You can come off your DMT and you’ll be fine.’ There is no evidence to support that,” she said.

Ms Parsons presented the findings from their study, acknowledging that their recommendations were based on existing literature that is “of poor quality.” They emphasized that they are simply offering “just a sense of what’s out there.”

What the Literature Shows

Overall, 3 observational studies were informative. A 2013 prospective study included 40 patients who discontinued DMTs after at least 5 years of continuous use and no new disease activity. After 46 months of follow-up, 90% of the patients remained free of clinical attacks and 85% had stable magnetic resonance imaging (MRI) findings (Olival GS, et al. Arq Neuropsiquiatr. 2013;71:516-520).

A 2015 study evaluated 303 patients aged ≥40 years who discontinued DMT after at least 3 years and had no clinical relapses in the past 5 years. Most patients resumed DMT because of increased disease activity after stopping, but older patients were less likely to do so (Kister I, et al. ECTRIMS Online Library. 2015;116635).

In 2016, the same investigators evaluated 485 patients who stopped DMT and 854 propensity-matched controls who continued DMT. The mean annualized relapse rates and time to first relapse were similar for those who discontinued (0.27, 1.81 years) and those who continued treatment (0.25, 2.01 years), but the time to confirmed disability progression was shorter among those who stopped DMT (Kister I, et al. J Neurol Neurosurg Psychiatry. 2016;87:1133-1137).

Other studies have found several factors that independently predict freedom from disease relapse after stopping DMT, including age ≥45 years, lack of disease relapse in the previous 4 years, and absence of contrast-enhancing MRI lesions. Risk of relapse has been found greater for patients stopping natalizumab than for those stopping platform DMTs, and increasing age has been associated with decreased likelihood of relapse in secondary progressive MS. It is also known that disease activity lessens with increasing patient age and that relapses have less impact on disease progression as time from disease onset increases.

Potential Candidates

The Canadian investigators concluded that it was reasonable to discuss discontinuing DMT for the following subsets of patients:

  • Patients with secondary progressive MS aged ≥55 years who have ongoing disease progression but have had no clinical relapses and no new brain or spinal cord MRI lesions in the past 12-24 months
  • Patients with stable RRMS aged ≥65 years who had no relapses or brain or spinal cord MRI lesions in the past 12-24 months
  • Patients with stable RRMS aged 55-65 years who had no new brain or spinal cord lesions in the past 5 years
  • Patients who are pregnant, trying to conceive, or are breastfeeding

A “Dangerous” Idea?

This idea was discussed at the session focusing on debates in MS. Some attendees hotly disagreed with this recommendation.

Samuel F. Hunter, MD, PhD, President, Advanced Neurosciences Institute, Franklin, TN, said, “When we treat with a DMT, we do it because we know 20% of those patients are destined to get worse. You’re saying we should stop the drug, and let those people who are going to progress do it, and we’ll treat them again.”

Dr Hunter added, “This practice gives license to payers to deny people therapy that physicians think they need. This is a very dangerous thing to put in the MS literature. It will only be used for harm to MS patients.”

Olaf Stuve, MD, PhD, Professor, Neurology and Neurotherapeutics, University of Texas Southwestern Medical Center, Dallas, commented, “We’ve all had middle-aged patients in whom we stop treatment, and they relapse. We should not use age and duration of treatment as the main factors in determining stopping….Is the patient really clinically stable, or is he responding to treatment? We might consider being relapse-free for 5 years to be an adequate response to the drug.”

This question is being further studied in a multicenter, randomized, controlled trial of DMT discontinuation in patients with MS aged ≥55 years who have had no relapses or brain MRI changes for at least 5 years using continuous DMT.

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