Discontinuation Of Disease-Modifying Therapies May Be The Right Move For Older Patients With MS

By Anna Goshua

The benefits of disease-modifying therapy (DMT) for multiple sclerosis may wane with age, according to a recent opinion article written by MS experts.

Treatment for MS typically begins after an initial episode. While research indicates that DMT is most effective in reducing relapses and disability progression in younger patients, there are limited data about the risks and benefits of DMT in older adults. Although patients 55 years and older account for nearly half of adults with MS, they have been excluded from the majority of key phase 3 DMT trials. As such, there is currently a lack of data to inform about if and when to discontinue treatment.

“It’s a very patient-centered issue because patients ask us all the time, ‘how long do I need to take these medications?’” senior author John Corboy, MD, said in an interview. “With the medications for MS, how long the benefits outweigh the potential risks remains unclear.” Dr. Corboy is professor of neurology at the University of Colorado at Denver, Aurora, and codirector of the Rocky Mountain MS Center, also in Aurora.

The viewpoint was published in the July 1 issue of JAMA Neurology.

“MS is a very variable disease. We treat people because we do better when we treat them but really, once you start someone on therapy, you don’t know how they would have done without it and, more importantly, if and when you can stop,” Fred Lublin, MD, who was uninvolved with the viewpoint, said in an interview. Dr. Lublin is the Saunders Family Professor of Neurology and the director of the Corinne Goldsmith Dickinson Center for Multiple Sclerosis at Mount Sinai Medical Center, New York.

Age and disease duration affect the course of MS. In younger patients, an adaptive immune response to the disease leads to acute relapses and focal inflammatory changes on MRI. Older patients, on the other hand, are more likely to experience progressive disability with minimal MRI changes and/or acute relapses or have a stable disease course without relapses or progression. The decrease in inflammatory events with increasing age may be why DMT is less effective in older adults.

“Modeling studies suggest that, on a group level, there may be no proven efficacy of DMT beyond approximately age 55 years,” wrote Dr. Corboy and colleagues.

Dr. John Corboy

Dr. Fred Lublin
However, age is not the only factor that affects how older patients respond to DMT. For instance, patients with late-onset MS who experience active focal inflammation may stand to benefit from DMT even in advanced age.

“Disease duration does matter. Recency of new disease activity does matter. Specific suggestions have to be made for an individual in the context of not only their age but also what’s happened to them recently, because it’s going to define, in part, what their response to medications will be,” Dr. Corboy said.

In addition to questions about the effectiveness of DMTs in older adults, there are also concerns about the safety of these medications in an aging demographic that is more vulnerable to infections. Not all DMTs pose the same level of risk.

“The biggest distinction is that, with older individuals and especially people who are disabled, there is a greater risk of infection in general. Medications which are more immunosuppressive will potentially pose a higher risk because of the combination of age and level of disability,” Dr. Corboy said.

In a 2020 study, an almost ninefold increase in severe infections was found among patients using wheelchairs who were treated with anti-CD20 agents for their MS.

“I always ask people how they’re tolerating their medications, if they feel that there’s a benefit associated with them, and also issues regarding cost, which can often become a problem after age 65 as people transition from private insurance to Medicare,” said Dr. Corboy.

When asking patients if they’ve thought about considering a trial off their medications, Dr. Corboy has found that patients are frequently concerned, especially if their MS has been stable.

“We had 377 people over the age of 55 respond to a survey about whether they’d consider a trial off their disease-modifying therapy, and over two-thirds of people said no. In talking to patients, they’re fearful that, if they go off their medication, they could have a recurrence of disease activity or their disease progression could worsen,” said Dr. Corboy. “Addressing patient concerns and fears about discontinuation is extremely important because it’s pervasive and it’s certainly appropriate to be concerned if you’ve been stable for a long period of time.”

In retrospective studies of patients who have discontinued DMTs, the risk of disease recurrence appears to be highest in younger patients with recent inflammatory disease activity rather than older adults. However, these studies are limited by their observational, nonrandomized designs and that most only enrolled patients using first-line therapies rather than higher-efficacy drugs that may be more likely to result in severe adverse events.

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Image credit: Jochen Sands/DigitalVision/Getty Images

“Well-organized data on what happens to people on disease-modifying therapies in the long term as they get older” is critical, said Dr. Lublin. This includes prospective, controlled, and randomized studies that enroll a broader population of patients, including older patients with longer MS disease duration.

Both Dr. Corboy and Dr, Lublin also called for the investigation of the viability of de-escalation strategies for patients on higher-efficacy medications.

“If someone is having complications related to a medication or we’re seeing that the risk may be too high as they age, perhaps they will de-escalate to a medicine that doesn’t have the same level of risk associated with it but maintains the benefit,” said Dr. Corboy. “But there are no published studies that I’m aware of.”

Dr. Corboy and Dr. Lublin have no relevant financial relationships to disclose.