Safe to Stop MS Disease-Modifying Therapy After Age 60?

Damian McNamara

October 19, 2018

BERLIN — Discontinuing disease-modifying therapy (DMT) for patients with multiple sclerosis (MS) who were older than 60 years did not lead to any significant difference in outcome measures in comparison with patients who continued treatment, a new study shows.

Researchers evaluated 600 MS patients who were older than 60 years; for 178 patients, or about one third, DMT was discontinued.

"In the first study we did, by just looking at those who stopped medication by age 60, we only had 10% who restarted medication, and only one relapse out of those 178 patients who stopped," Le Hanh Hua, MD, staff neurologist at the Cleveland Clinic Lou Ruvo Center for Brain Health in Las Vegas, Nevada, told Medscape Medical News.

In a follow-up study, Hua and colleagues focused on changes in quality of life and performance measures. "And there was no harm — patients do not worsen in terms of their walking speed, hand function, or depression."

Hua presented the findings here at the 34th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) 2018.

Age Before Stability?

"There have been prior discontinuation studies that have not been as successful as we wanted them to be," Hua said. She noted that many of these studies investigated stopping DMT on the basis of disease stability.

In contrast, the current study assessed patient age as a factor. "The idea is, when you're young with early MS, your disease is overwhelmingly inflammatory," she said. "When you get older, the overt inflammation tends to die down."

Given this natural history of disease, continuing immunomodulatory therapy in older patients with MS could increase the risk for infections and potential side effects of DMT, Hua said.

The practice, however, remains controversial. A literature review of six observational studies presented at the 2017 annual meeting of the Consortium of Multiple Sclerosis Centers found support for stopping DMT after age 65, as previously reported by Medscape Medical News.

However, the researchers noted that the data were of poor quality and were generally insufficient to make a broad recommendation.

"There is a lot of discussion, and we are in urgent need of scientific evidence," Sandra Vukusic, MD, PhD, professor of neurology and head of the Multiple Sclerosis Clinic at the Lyon University Hospital, France, who was unaffiliated with the study, told Medscape Medical News in an interview here.

In the current study, Hua and colleagues compared patients who discontinued DMT (both before and after they stopped therapy) and patients who continued treatment. All participants had received DMT for 2 or more years at baseline.

Statistically, the researchers compared all three groups using separate mixed-effects linear regression models. They also studied how outcomes might have changed over time, using an interaction term between the time and treatment group to study the trajectory of the outcome. They controlled for age at diagnosis, sex, MS course at baseline, time on DMT, baseline DMT, and ambulation status at age 60. They also used pairwise comparisons among the three treatment groups.

Only One Significant Difference

Most patients older than 60 who discontinued DMT remained off DMT.

Hua reported no significant differences in the graphic slopes of results comparing those who continued DMT and those who did not, either before or after they stopped DMT.

Only the EQ-5D health questionnaire mixed-effects linear regression model with the interaction term was statistically significant (P = .043). In addition, the slope relating time to EQ-5D was significantly different when comparing continuers to discontinuers before discontinuation (0.009; 95% confidence interval, 0.002 - 0.016; P = .015).

Without the interaction term, there were no significant differences between the three groups in outcomes as measured on the Multiple Sclerosis Performance Scale, the Timed 25-Foot Walk Test and the Patient Health Questionnaire–9. The investigators also did not find any statistically significant differences among the pairwise comparisons.

In addition, Hua and colleagues found no significant association between treatment group and presence of gadolinium-enhancing or new T2 lesions.

"Overall, stopping DMT appears to have minimal effect on outcomes over time," the researchers note.

Additional Perspective

Some previous research suggests that treatment withdrawal can be successful, particularly among people with secondary progressive MS. "There is evidence from natural history studies that disease activity decreases with age; disease activity is much more important in younger people than older people," Vukusic said.

So in that context, "we start to discuss if it is really useful to maintain the drug that might have side effects, sometimes very serious side effects.

"But you also have patients who do have relapses after the age of 55, 60, or 65," she added. The controversy about stopping DMT after a certain age may not be resolved until more evidence emerges.

A number of investigations are underway. "In France, we have a clinical trial that just started in which we take patients with secondary progressive disease without clinical or MRI disease activity in the past 5 years," she said. "We will either stop or continue the drug, and the patients will be followed for the next 3 years to see if there is a difference."

Dr Hua receives personal compensation for speaking, consulting, or advisory board activities from Biogen, Genzyme, Genentech, Novartis, Teva, EMD Serono and TG Therapeutics. Dr Vukusic has disclosed no relevant financial relationships.

34th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) 2018. Abstract P1230, presented October 12, 2018.

Follow Damian McNamara on Twitter: @MedReporter. For more Medscape Neurology news, join us on Facebook and Twitter.


Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.