Older Adults With MS May Consider Discontinuation of Disease-Modifying Therapy

There is no significant difference in relapse or new disease activity on magnetic resonance imaging (MRI) scans in older adults presenting with stable multiple sclerosis (MS) who continued or discontinued disease-modifying therapy (DMT), according to study findings published in the journal Lancet Neurology.

MS usually manifests in young adults and new disease activity decreases with age, such that most clinical trials for DMT exclude individuals aged 55 years and older. Research suggests that risk for relapse of disease activity following discontinuation of DMTs is higher among younger patients who demonstrate MRI activity or have experienced more recent relapses.

Researchers in the United States sought to determine whether discontinuation of DMT increases the risk for disease recurrence in patients with MS older than 55 years of age compared with patients who continued taking the DMT. All eligible patients demonstrated no disease activity within the past 5 years or new lesion changes on MRI scans within the past 3 years.

The researchers conducted a multicenter, single-blind, phase 4, noninferiority, randomized trial, Discontinuation of Disease Modifying Therapies (DMTs) in Multiple Sclerosis (MS; DISCOMS; ClinicalTrials.gov Identifier: NCT03073603), enrolling 259 participants older than age 55 years with MS between May 2017 and February 2020 from 19 MS centers across the United States. The researchers randomly assigned these 259 participants into 2 groups — 128 individuals into the continue group and 131 individuals into the discontinue group.

Participants underwent baseline brain MRI scans using 1.5 Tesla or stronger magnet strength within 6 months of study enrollment. These MRI scans were repeated at 6, 12, and 24 months. Clinicians determined MS relapses using the Expanded Disability Status Scale (EDSS). Any new or expanding brain lesions on MRI scans or MS relapses per the EDSS indicated new disease activity.

Additionally, the study participants also underwent the Symbol Digit Modality processing speed test (SDMT) and completed questionnaires, including the Neuro-QOL short form, SymptoMScreen, Patient-Determined Disease Steps (PDDS), at baseline and at 6, 12, 18, and 24 months.

Over the 2-year follow-up period, 6 (4.7%) of the 128 participants in the continue group and 16 (12.2%) of the 131 in the discontinue group experienced relapses or developed new or expanding brain lesions upon MRI scanning (Difference, 7.5%; 95% CI, 0.6-15; P =.52). Using the predetermined noninferiority margin of 8%, the researchers were unable to completely reject the null hypothesis that discontinuation of DMT was inferior to continuation.

More mild and serious adverse events (AEs) occurred in the discontinue group compared with the continue group. The most common adverse event was upper respiratory infections.

Among the patients with MS who continued their DMT, 109 (85%) of 128 participants experienced a total of 347 mild adverse events, and 18 (14%) participants experienced a total of 30 serious adverse events. Among patients who discontinued their DMT, 104 (79%) of 131 participants experienced a total of 422 mild AEs, and 20 (16%) participants experienced a total of 40 serious AEs.

“We…could not conclude whether disease-modifying therapy discontinuation is non-inferior to continuation in patients older than 55 years with multiple sclerosis and no recent relapse or new MRI activity,” the researchers wrote. They added, “Discontinuation of disease-modifying therapy might be a reasonable option in patients older than 55 years who have stable multiple sclerosis, but might be associated with a small increased risk of new MRI activity.”

Study limitations included lack of a placebo control group, use of older, injectable medications in the continue group instead of newer, more effective DMTs, and lack of generalizability outside of the population of patients with MS who were aged 55 years and older.

Disclosures: Several study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see original source for full list of disclosures.