Comorbidities in MS: Prevalence, Impact, and Management

By Debra L. Beck

Comorbidities are common in patients with multiple sclerosis (MS), can impact treatment decisions, and require a multidisciplinary approach to management, including careful attention to lifestyle issues, said Patricia Melville, RN, MSN, NP-C, MSCN, in a presentation at the virtual annual meeting of the Consortium of Multiple Sclerosis Centers (CMSC).

“Recognizing and managing comorbidities early in the disease course will have a positive impact,” said Ms. Melville, who is a clinical instructor at Stony Brook University in New York and an adult care nurse practitioner/clinical nurse specialist at MS Comprehensive Care Center at SUNY Stony Brook.

Comorbidities, as distinct from the expected complications of the disease, are associated with reduced functional status and quality of life in patients with MS, along with greater lesion burden and mortality. Their pathogenesis is complex, said Ms. Melville, and the topic of several ongoing studies, including some that are looking at whether patients with MS might have genetic predispositions to certain diseases, including cardiovascular disease and psychiatric disorders such as bipolar disease, depression, and schizophrenia.

Patricia Melville
Poor health behaviors play an important role in the development of comorbidities. These include core health behaviors, such as obesity, lack of exercise, smoking, and substance use disorder. But disease modifying therapies (DMTs) themselves also may come with complications and adverse events that can promote comorbidities.

“Comorbidities in MS have a negative impact on the brain tissue and the central nervous system reserve. We know that they assault the central nervous system,” said Ms. Melville. And without question, they increase hospitalizations and mortality, she added, showing findings from several studies on the topic.

Comorbidities also increase the risk of an MS relapse. In a Canadian study that included 885 individuals with MS, those with three or more comorbidities (the most common ones were anxiety in 40%, depression in 21%, hypertension in 18%, migraine in 18%, and hyperlipidemia in 12%) had a higher rate of relapse over 2 years, compared with those with fewer comorbidities.

Credit: Multiple Sclerosis Journal

Credit: Journal of Neurology, Neurosurgery & Psychiatry

Common Comorbidities

The comorbidities most prevalent in MS are depression and anxiety, each seen in almost one-quarter of MS patients, followed by hypertension, hyperlipidemia, and chronic lung disease. The risk of malignancy also is increased, including cancers of the cervix, breast, and digestive systems. Increased risks for meningiomas and cancers of the urinary system also have been reported.

A recent registry study from Norway looked at MS patients, their siblings without MS, and a control group of individuals who did not fit into either category. They found that cancer risk was increased in MS patients, compared with controls, with most cancers seen involving respiratory organs, urinary organs, and the central nervous system.

“There are also some sex differences in comorbidities … hypertension, heart disease, and hyperlipidemia are more common in men, while in women, you see more problems with depression, anxiety, and lung disease,” Ms. Melville said. Both men and women with MS have a higher burden of comorbidities than men and women in the general population.

In a prospective study that looked at cardiovascular risk factors in patients with MS and healthy controls, more than half of individuals with MS smoked, compared with about one-third of healthy controls (52% vs. 37%, respectively). About half (49.9%) of MS patients had two or more cardiovascular risk factors versus 36% of healthy controls (both P values significant).

“Patients with MS and hypertensions and heart disease showed decreased gray matter and cortical volume, patients with MS and obesity had an increased T1 lesion volume, and patients with MS who smoked had a decrease in brain volume,” reported Ms. Melville.

Management: Timely, Multidisciplinary, and Lifestyle Oriented

“How do we manage comorbidities in our patients? We really need to follow a multidisciplinary and a multidimensional approach,” said MS. Melville. Beyond the MS care team, primary care should be involved, along with any other specialists deemed necessary.

“We really want to encourage our patients to integrate lifestyle management with conventional medicine,” she added, and work on those modifiable risk factors like smoking, exercise, diet, and alcohol and substance use disorder. Also important is attending to your patients’ sleep quality and quantity and helping them with stress management. “We want them to have some sort of physical activity, as much as possible, even those who are wheelchair confined,” she added.

The American Academy of Neurology (AAN) and the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) have included in their recent guidelines a recommendation to include counseling about comorbid disease and adverse health behaviors when initiating a DMT. ECTRIMS guidelines suggest considering patient comorbidities (among other factors) when considering a DMT switch.

In terms of how individual comorbidities might affect DMT efficacy, Ms. Melville noted that injectable interferon-betas have “contraindications, considerations, and warnings” in several comorbid conditions, including patients with depression or suicidal thoughts. Careful monitoring also is needed for those with abnormal hepatic function, thyroid disease, and a history of myelosuppression, as well as in women who are pregnant or breast feeding. Other risks with the interferon-beta DMTs include seizures and thrombotic microangiopathy.

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“This is going to be a case-by-case basis where you’re going to just weigh the risks and the benefits and have a discussion with the patient about that,” said Ms. Melville.

Fingolimod also has several contraindications, including recent myocardial infarction, unstable angina, stroke, transient ischemic attack, and heart failure. The agent also is contraindicated in patients with heart block or Sick Sinus syndrome, unless the patient has a pacemaker, and in those with cardiac arrhythmias requiring treatment. Siponimod has many of the same contraindications.

“We do have some current dilemmas,” said Ms. Melville. The clinical trials of DMTs have largely excluded older patients and those with comorbidities. “So when the drug is approved, we’re using them in a population that has not been studied and the findings from those trials lack generalizability.” There is a need for more observational studies that include this population and for clinical trials looking directly at the effect of comorbidities and DMTs.

Ms. Melville concluded by saying, “We want to encourage our MS patients to engage in wellness, health, maintenance, and vascular risk factor control programs, and we want to use a model of shared decision-making. Careful consideration of comorbidities also must be included when recommending and considering DMTs.”