Worsening of Disability Evident in Older Patients Who Stop DMTs

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by Marisa Wexler MS |

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While older multiple sclerosis (MS) patients whose conditions are stable commonly stop using disease-modifying therapies (DMTs), a study indicates this decision can shortly lead to a marked disease worsening in a substantial portion of them.

“Our results raise important questions about the accepted practice of discontinuing medications once MS patients are in their 50s and 60s,” Dejan Jakimovski, MD, PhD, a professor in the neurology department at the State University of New York at Buffalo and a study co-author, said in a press release.

The study, “Discontinuation of Disease Modifying Therapies is Associated with Disability Progression Regardless of Prior Stable Disease and Age,” was published in Multiple Sclerosis and Related Disorders.

DMTs have been proven to slow MS progression and more than a dozen are currently approved. They broadly work by reducing the activity of the immune system; MS is caused by abnormal immune activity that damages the nervous system.

As patients age, active inflammation is thought to play less of a role in disease progression, making DMTs less beneficial for older patients with more progressed disease. Since DMTs can be costly and carry a risk of side effects, the relative benefit of continuing these treatments in older patients has been thought to be small.

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“It’s generally accepted that these older patients won’t benefit with the currently available disease-modifying medications, but some of the studies that those conclusions were based on involved older medications,” Jakimovski said. “There are better DMTs now, and clinical trials have also improved.

“It’s becoming a real issue: Do we treat these older progressive MS patients, and do the currently available medications work?”

Using data from the New York State MS Consortium, one of the largest statewide MS registries in the U.S., the researchers identified 216 MS patients who had discontinued a DMT after at least six month of use.

Among the patients, 85.6% were female, and their average age was 50.6; 37.5% were older than 55. At the time of discontinuation, just over half (54.2%) had relapsing-remitting MS (RRMS), and the rest had secondary progressive MS (SPMS). Their average disease duration was 18.1 years, and patients were followed in this study for an average of about 4.6 years.

Most (57.4%) had been on interferon-beta treatments. Other common DMTs prior to discontinuation were glatiramer acetate (sold as Copaxone, among others; 18.5%) and Tysabri (natalizumab; 6%).

A majority of these patients (161 or 72.5%) also had stable disease prior to discontinuing — defined as no meaningful changes in disability, as measured by the Expanded Disability Status Scale (EDSS). The remaining 55 had progressing disease (i.e., worsening EDSS scores) prior to discontinuing.

“We selected patients who were previously clinically stable. This preselection criterion is important because usually these DMT discontinuations occur in patients who have been stable for a long time and no new activity is expected,” Jakimovski said.

After discontinuing with their DMTs, 53 (32.9%) of the previously stable patients experienced worsening disability progression. By comparison, 10 (18.2%) of those with evidence of progression before stopping treatment had evidence of further progression after discontinuing.

Further analysis showed no difference in the risk of progression after discontinuing based on age or MS type.

“The rate of disability worsening was not different between patients that stopped their medication, regardless if they were younger or older than 55 years old. Moreover, these changes also occurred in both relapsing-remitting and progressive MS patients,” Jakimovski said.

Among SPMS patients, 40% of those with stable disease — 22 out of 55 people — experienced worsening after discontinuing DMT treatment, the study found, while 16% SPMS patients (4 of 25) with already-progressing disease had further progression.

Other analyses suggested that patients with more substantial disability (a score of six or higher on the EDSS) were more likely to experience worsening disease progression throughout the studied period. In total, 40.7% of patients with EDSS scores of six or greater experienced disease progression, compared with 15.4% of those with less severe disease.

“During the period before and after DMT discontinuation, MS patients with higher levels of disability had a greater percentage of [worsening disability] when compared to less disabled patients, with no clear relation with age,” the researchers wrote.

“In conclusion,” they added, “previous disease stability and older age are not reliable predictive factors for continued stability after DMT discontinuation. Up to a third of MS patients that discontinue treatment experience DWP [disability worsening/progression] afterwards and this finding was present in both RRMS and SPMS subtypes.”

A main study limitation noted by the researchers is the lack of a comparison group of patients who continued taking their DMTs.

“The main caveat could be that these patients were going to have this progression regardless of whether or not they discontinued their medications,” Jakimovski said. “However, these limitations are still not sufficiently explaining the significant progression in a large percentage of the patients.”

A clinical trial, an extension of the DISCOMS study (NCT04754542), is comparing groups of older MS patients who have discontinued or stayed on DMTs. It is due to conclude in August.

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