MILAN –
In the multicenter, randomized, controlled, noninferiority DOT-MS trial, inflammatory activity came back in 17.8% of 45 participants who discontinued DMT, researchers reported at the 9th Joint ECTRIMS-ACTRIMS Meeting.
“Because the number of participants with active disease – relapse or MRI activity – was higher in the discontinuation group, and this difference between the groups exceeded our predefined threshold, we prematurely terminated the trial in its current form,” said Eline Coerver, a graduate student with VU University Amsterdam, in an interview.
Previous studies have offered a mixed picture about whether stopping DMT is a good idea when patients with MS are doing well.
“Observational studies suggest that discontinuation of first-line DMTs, or platform therapies, might be safe in patients with MS who have been stable for a long period of time, meaning they did not have any clinical relapses or inflammatory MRI activity – new or contrast-enhancing lesions on MRI,” Ms. Coerver said. “These studies also suggest that patients with higher age have a lower risk of disease activity after DMT discontinuation.”
Discontinuation of DMTs can spare patients from side effects and the cost of the drugs. However, a phase 4 trial published earlier this year in The Lancet Neurology could not determine that stopping DMTs is noninferior to continuing treatment in patients with MS aged 55 and older.
“Six (4.7%) of 128 participants in the continue group and 16 (12.2%) of 131 in the discontinue group had a relapse or a new or expanding brain MRI lesion within 2 years,” the researchers reported.
For the new study, Ms. Coerver and colleagues recruited patients with relapse-onset MS aged 18 years or older who hadn’t had any relapses or substantial MRI activity in the last 5 years. The subjects were randomly assigned to discontinue DMT (interferon, glatiramer acetate, teriflunomide, or dimethyl fumarate) or continue taking the therapy for 2 years.
At pre-set interim analyses, the researchers would look for signs of inflammatory disease activity, which they defined as a confirmed relapse or three or more new T2-lesions or two or more contrast-enhancing lesions detected via MRI.
At the time of cessation in March 2023 (median follow-up = 12.0 months, interquartile range 7.0-20.0), the study had recruited 89 subjects: 67.4% female, mean age 53 (SD, 7.8). Just over half (50.6%) were randomized to discontinue treatment. Of the 45 in the discontinuation group, 8 (17.8%) developed inflammatory activity (7 significant MRI activity, 2 relapses) versus none of the 44 who continued therapy.
Interpreting the results
Two MS clinicians who are familiar with the study findings but weren’t involved with the research were reached for comment.
Katherine Knox, MD, a physiatrist and associate professor who specializes in MS care at the University of Saskatchewan, Saskatoon, said in an interview that the new study is useful “because it affirms that an appropriate stopping recommendation cannot be made primarily on the basis of a standard number of years without disease activity.”
In regard to the percentage of patients who had a recurrence of inflammatory activity (17.8%), Dr. Knox said “ideally patients can be triaged for stopping therapy appropriately with a much lower risk for return of disease activity based on their individual risk factors – i.e., under 2%.”
Michael J. Olek, DO, associate professor of neurology at Touro University Nevada, Henderson, took a different view. He said he does not discontinue medication in patients with MS even if they’re stable for 5 years.
“I am waiting for trials that show that discontinuing medication is OK for the patient. To date, there are no studies showing that stopping medication is a good idea,” he said. “The immune systems slows as people age, so there may be a point in a person’s lifetime when medication used to slow the immune system is no longer needed. But until then I will continue medication for all multiple sclerosis patients.”
Moving forward, study lead author Ms. Coerver said “there are large differences between patients, and there is still room for discussion regarding what percentage of disease activity can be accepted after DMT discontinuation. The most important point is to inform patients about the risks of discontinuation so that each individual patient can make a well-informed decision.”
The study was funded by the Netherlands Organization for Health Research and Development and Stichting MS Research. Ms. Coerver reports no disclosures; some other study authors report various disclosures. Dr. Olek reports no disclosures. Dr. Knox discloses research funding from the Saskatchewan Ministry of Health to evaluate and monitor long-term outcomes in MS.