Risks of ending disease-modifying therapy may be ‘minimal’ in older, stable adults with MS

Key takeaways:

• Disease-modifying therapy de-escalation may be safe in certain older patients with MS.
• More data are needed to understand the risks and benefits of discontinuation in this population.

WEST PALM BEACH, Fla. — It may be sensible for older patients with MS who have prolonged stability to cease disease-modifying therapy, but more data are needed to understand the effects of discontinuation in this group, an expert said.

“There are substantial changes — pathological, immunological, clinical, radiological — that occur over time as people age with their MS,” John R. Corboy, MD, professor of neurology at the University of Colorado Anschutz Medical Campus, said during his presentation at ACTRIMS. “Not surprisingly, there can be some differences in how people respond to the presently available [disease-modifying treatments (DMTs)].”

DMTs have a “relatively modest impact” in older patients, according to Corboy. There are limited data on the risks and benefits of DMTs in older patients, as clinical trials often exclude those aged 55 years and older, he said.

The risks associated with DMTs may be greater in older patients due to factors such as comorbidities, infections and poor vaccine response, Corboy added.

He cited data that show about 40% of patients with MS aged older than 60 years in the United States still use DMT. Peak use occurs between age 41 to 50 years.

Corboy reviewed data from the DISCOMS and DOT-MS studies to illustrate the effects of DMT discontinuation in older adults.

In DISCOMS, the primary outcome was new relapse or new or expanded MRI-detected lesion. It was a noninferiority trial, with a noninferiority margin of 8%.

Over an average follow-up period of 22 months, 12.2% of discontinuers vs. 4.7% of continuers achieved the primary outcome, Corboy said. However, the trial failed to demonstrate noninferiority. The main difference between groups was a higher risk for new T2 lesions in discontinuers (10.7% vs. 3.91%), Corboy added. The researchers found that patient satisfaction was higher in patients who discontinued DMT vs. those who continued.

In DOT-MS, researchers stopped the trial early after finding significantly more new disease activity among discontinuers (17.8%) vs. continuers (0%) over a median of 15 months of follow up. When modifying the criteria from “significant” MRI activity to “any” MRI activity, they found that 24.4% of discontinuers met the criteria vs. 2.3% of continuers.

The difference in disease recurrence in DOT-MS compared with DISCOMS could be due to the younger population in DOT-MS (median age 54 years vs. mean age 63 years in DISCOMS) as well as shorter time since last relapse (median 9 years in DOT-MS vs. mean 14 in DISCOMS), Corboy said.

Overall, Corboy reported the increased risk for new relapse and worsening disability or symptoms in DMT discontinuers aged older than 60 years with prolong stability is “really minimal when compared to continuers.”

“The greatest risk is that of new disease activity in the MRI scan of one or two lesions of unclear significance clinically in the long run,” he said.

Additionally, the role of age, disease activity and duration as well as the level of disability “do not appear to play the same level of predictive role as seen in younger patients,” he added.

“We need to know more about different mechanisms of action in these older, more stable populations. We need in general more data on risks and benefits of treatment in older patients, especially in progressive patients,” Corboy said. “We also need to understand more about the role of de-escalation. There’s a lot of people who would potentially be interested in discontinuation but are concerned about it. Maybe de-escalation would be one way to go. There are de-escalation studies underway.”

He ended his talk with a note that patients who discontinue treatment should still be monitored and potentially restart treatment if necessary, and “aging itself plays a role” in functional decline, so “we have to pay attention to other problems as people age.”

References:

Corboy JR, et al. Lancet Neurol. 2023;doi:10.1016/S1474-4422(23)00154-0.

Coerver EME, et al. JAMA Neurol. 2025;doi:10.1001/jamaneurol.2024.4164.