Comorbidities in Multiple Sclerosis: Effects on DMTs, the Treatment Team, and More

Multiple sclerosis (MS) is associated with a compendium of comorbid conditions that exert a significant influence on patient morbidity, mortality, and quality of life (QoL). The chronic, inflammatory nature of MS contributes to a high rate of comorbidities, which in turn contributes to greater MS disability and a poorer disease course.¹ Findings from a 2016 study conducted in Australia suggested that people with MS have a much higher risk for certain conditions such as hypertension, dyslipidemia, asthma, psoriasis, eczema, and anemia compared with the general Australian population.¹

The patterns of comorbidities in MS are often predictive of outcomes. Kowalec, et al² reported that patients with MS with comorbid migraine or hyperlipidemia and patients with a high comorbidity burden consisting of 3 or more diagnosed conditions were more likely to experience MS over a 2-year period.

As Ruth Ann Marrie, MD, PhD, director of the multiple sclerosis clinic at the University of Manitoba Health Sciences Centre in Winnipeg, Canada, and co-investigator in multiple studies on MS comorbidity, told Neurology Advisor, “Several comorbid conditions are associated with greater disability progression including depression, diabetes, hypertension, and hyperlipidemia.” Psychiatric comorbidities, including depression, anxiety, and bipolar disorder have higher reported prevalence in the MS population, although studies report widely varied estimates. A 2015 study by Marrie, et al³ found that while the incidence of all 3 psychiatric comorbidities was higher in women, the burden for depression in particular was significantly higher in men.

Managing Comorbidities

Having a higher burden of comorbidities is also associated with greater disability progression and lower QoL, as well as increased healthcare utilization and mortality, Dr Marrie said, which therapeutically suggests preventing and treating comorbidities as a means of improving outcomes. However, the range and diversity of possible comorbid conditions that patients with MS experience requires multidisciplinary care. “Comorbid conditions are often managed by other providers,” she explained. “Diabetes for example, would typically be managed by a primary care provider or endocrinologist as this condition does not fall within the usual scope of practice of a neurologist,” she said, noting that some conditions such as depression or anxiety disorders might be managed by a provider within the MS care team, a diversified group of trained individuals that also includes MS nurses, occupational therapists, physical therapists, dieticians, and social workers in addition to the neurologist. Treatment of comorbid conditions is equally important to improving MS outcomes, Dr Marrie said.

Impact on Disease Modifying Therapies

The effects of specific comorbidities on disease modifying therapies (DMTs) used to treat MS have been only minimally studied. Dr Marrie pointed out that comorbid conditions and their treatments may have an impact on the safety and tolerability of some DMTs for MS. “For example, individuals with comorbid autoimmune disease are at increased risk of developing new autoimmune disorders when treated with alemtuzumab as compared to those without such conditions. Individuals with diabetes and uveitis are at increased risk of developing macular edema when treated with fingolimod,” she said. “Individuals with migraine may experience increased headache frequency or severity when taking inteferon-beta. Thus, the choice of DMT should involve consideration of the individual’s health overall, as well as their preferences regarding adverse effect profile, route of administration, and so on.”

Just as important as the real impact of comorbid conditions on the pharmacodynamics of DMTs is the influence of the perceived impact on treatment decisions. Zhang and colleagues⁴ were the first investigators to examine the correlation between comorbidities and the decision to initiate treatment in a cohort of 10,698 patients with MS. They found that the likelihood of DMT decreased with increasing numbers of comorbid conditions. In addition, specific conditions, including ischemic heart disease and anxiety — and to a lesser degree, hyperlipidemia, chronic lung disease, and bipolar disorder — were associated with a lesser likelihood of initiation of DMTs.⁴ The researchers noted that their definitions of ischemic heart disease and anxiety were not highly sensitive, probably resulting in an underreporting of these comorbidities.⁴

Cancer and MS

A confounding effect that is sometimes observed in studies is a lower rate of cancer in patients with MS compared with the general population. Gaindh and colleagues⁵ found that cancer in patients with MS was more likely to be associated with DMT use, implicating DMT as the likely trigger. Dr Marrie observed that the literature regarding the association between MS and cancer is quite mixed and the overall trend toward a lower risk for cancer in patients with MS does not appear to be a uniform effect, as an increased incidence of bladder cancer has been demonstrated. “Several factors are likely to influence cancer risk in MS in variable ways — there is a possibility of improved immune surveillance secondary to MS, which could potentially reduce cancer risk. However, increased obesity, physical inactivity, and smoking can increase cancer risk, as may exposure to some disease-modifying therapies,” she said.

Patient Responses

A single study by Chouhfeh, et al⁶ found that autoimmune comorbid conditions developed sooner in patients with MS taking DMTs, but the results of that study have not been replicated. The presence of comorbidities may also have an impact on patient adherence to prescribed DMTs, particularly due to tolerability concerns. Dr Marrie noted that current research has not determined whether treatment efficacy is affected by comorbid conditions. She recommended support throughout the DMT treatment process to manage adverse effects, drug interactions, and other potential challenges. 

References

1. Tettey P, Siejka D, Simpson S Jr, et al. Frequency of comorbidities and their association with clinical disability and relapse in multiple sclerosis. Neuroepidemiology. 2016;46:106-113.
2. Kowalec K, McKay KA, Patten SB, et al. Comorbidity increases the risk of relapse in multiple sclerosis: A prospective study. Neurology. 2017;89:2455-2461.
3. Marrie RA, Fisk JD, Tremlett H, et al. Differences in the burden of psychiatric comorbidity in MS vs the general population. Neurology. 2015;88:1972-1979.
4. Zhang T, Tremlett H, Leung S, et al. Examining the effects of comorbidities on disease-modifying therapy use in multiple sclerosis. Neurology. 2016;86:1287-1295.
5. Gaindh D, Kavak KS, Teter B, et al. Decreased risk of cancer in multiple sclerosis patients and analysis of the effect of disease modifying therapies on cancer risk. J Neurol Sci. 2016;370:13-17.
6. Chouhfeh L, Kavak KS, Teter BE, Weinstock-Guttman B.  Disease modifying therapies use associated with comorbid autoimmune diseases in multiple sclerosis patients. Mult Scler Relat Disord. 2015;4:228-233.