Comorbidities common in MS patients in clinical trials, study finds

Nearly half of all multiple sclerosis (MS) patients who participated in clinical trials — including global, pivotal studies — had one or more comorbidities, or coexisting conditions, the most common being depression and high blood pressure, a meta-analysis study found.

While the rate of patients with comorbidities “may be higher than expected for clinical trial populations,” these people may still be “underrepresented compared with the general MS population,” the researchers wrote.

Because these conditions can affect how MS progresses and how well disease treatments work, it is important to make sure that clinical trials include a diverse range of participants who mirror the general MS population.

The study, “Investigating the Prevalence of Comorbidity in Multiple Sclerosis Clinical Trial Populations,” was published in the journal Neurology.

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Common comorbidities in MS patients involve mental health, cholesterol levels

People with MS commonly have other co-occurring conditions, the most frequent being mental health problems such as anxiety and depression, high blood pressure (hypertension), high levels of fats in the blood (hyperlipidemia), and chronic lung diseases.

These co-occurring conditions are more common as a person ages, and they can worsen disease severity, leading to more MS relapses and disability progression.

It’s generally well established that clinical trials tend to exclude many patients with comorbidities, raising concerns as to whether trial findings accurately apply to the real-world populations with the condition. Whether this is also true for MS, however, remains to be addressed.

A team of researchers in the U.S., Canada, and Sweden conducted a meta-analysis of published studies to determine how well people with comorbidities have been represented in MS clinical trials.

They combined data from 17 Phase 3 clinical trials in now approved MS disease-modifying therapies, such as Ocrevus (ocrelizumab), Tysabri (natalizumab), Gilenya (fingolimod), Tecfidera (dimethyl fumarate), Lemtrada (alemtuzumab), and certain interferon-based therapies. In total, these studies involved 17,962 patients.

Most of the Phase 3 trials enrolled people with relapsing forms of MS, marked by episodes of new or worsening symptoms (relapses). Three enrolled people with progressive MS, where symptoms worsen gradually over time.

Almost half (46.5%) of trial participants had at least one co-existing condition — 25% had one comorbidity, 11.4% had two, and 6% had three or more. However, there was a lot of variability across clinical trials, with rates of participants with comorbidities ranging between 35.8% and 77.3%.

In general, depression and hypertension were the most common comorbidities, affecting 16.5% and 10.2% of all trial participants.

Migraine more common with relapsing MS, hypertension with progressive forms

When two comorbid conditions were present, they commonly included one cardiometabolic condition and one mental health problem. Three comorbidities most frequently included three cardiometabolic conditions.

“Little is known about the patterns of comorbidity in MS,” the researchers wrote. “Additional investigation into [the] prevalence of these dyads and triads are needed to understand how representative these may be to the general MS population.”

Some differences were seen in medical conditions by MS type. Migraine was more common in people with relapsing MS forms, whereas hypertension and hyperlipidemia were more common in those with progressive MS.

Over time, from 2006 or earlier to 2013 or later, there was an increase in the prevalence of diabetes and hypertension.

“We observed an increase in the prevalence of diabetes and hypertension in the trials over a fifteen-year period, yet the prevalence of most comorbid conditions decreased or remained constant over time,” the researchers wrote.

Finally, the researchers observed that being older or a woman was linked to having more medical conditions alongside MS, although there were no differences by race. As expected, having more comorbidities associated with greater disability levels.

“It will be important to further understand the influence of comorbidity on outcomes in the clinical trial setting,” they concluded. “Future work investigating potential differences in treatment response according to comorbidity status are warranted.”