Dr Burcu Zeydan Explains Why DMTs Become Less Effective as Patients Age

September 24, 2020

Disease-modifying therapies (DMTs) are primarily effective through immunomodulation, in that they target relapse prevention, said Burcu Zeydan, MD, assistant professor of neurology, assistant professor of radiology, at Mayo Clinic.

Aging has a noticeable effect on why disease-modifying therapies become less effective as patients get older, especially when you account for the decreases in both CNS reserve and postrelapse recovery potential, explained Burcu Zeydan, MD,assistant professor of neurology, assistant professor of radiology, at Mayo Clinic.

Transcript

Why do disease-modifying therapies (DMTs) lose efficacy as patients with MS age?

Well, when we consider aging-related observations about relapse recovery progression and CNS reserve in multiple sclerosis, it is not surprising that the disease-modifying therapies lose efficacy as patients with MS age. As the CNS reserve decreases with age, the postrelapse recovery potential decreases with age as well. Most importantly, the clinical and subclinical relapses become less frequent with age, while evolution to progressive illness increases with age. So, the existing DMTs are primarily effective through immunomodulation. They target relapse prevention, and they are not specifically meant to prevent progression.

It seems like the optimal window for existing numbered literary DMTs is earlier in life, when the disease is more likely to be active, by preventing some symptomatic relapses and asymptomatic subclinical activity. On the other hand, the currently available DMTs seem to lose efficacy with aging. We know that aging plays a major role in the development of a progressive disease course, with neurodegeneration becoming more prominent and severe disability being closely related to progressive illness.

In a 2017 meta analysis from the NIH, all randomized and blinded MS clinical trials were evaluated. And the efficacy of the DMTs was clearly found to be lowered in older patients compared to younger patients with MS. Although the authors emphasized that efficacy of immunomodulatory DMTs is on disability worsening, strongly decreased with advancing age, they also emphasize that the patient's specific genetic and environmental factors are still important in making treatment decisions.

Overall, the decline in the efficacy of DMTs with older age in MS seems to reflect the impact of aging on the relationship between reserves, relapses, recovery, and progressive MS z-scores mechanisms.