Comorbidity Burden Adversely Associated With MS Disease Activity

A greater comorbidity burden is associated with increased multiple sclerosis (MS) disease activity in patients, according to study results published in JAMA Neurology.

Although previous research has indicated a link between the presence of comorbidity and worse clinical outcomes in MS, little is known about the effect of comorbidity on measures of disease activity, such as relapse rate and lesion accrual.

Using data from phase 3 clinical trials of MS disease-modifying therapies, a team of researchers determined the association between comorbidity and disease activity in MS.

Information on demographic and clinical characteristics, as well as comorbidities, such as cardiovascular, metabolic, vascular, and autoimmune diseases, were collected from all eligible participants.

Primary study outcome was disease activity during follow-up, defined as disability worsening (measured using the Expanded Disability Status Scale [EDSS]), relapse, or any lesion activity on magnetic resonance imaging (MRI).

A total of 17 trials with 16,794 individuals (67.2% women) were included in the analysis, with 45.4% having at least 1 comorbidity. In the 2-year follow-up, 61.0% (I²=97.9%)of the pooled trials had evidence of disease activity.

After adjustment for age, sex, treatment duration, and baseline EDSS, the researchers noted that the presence of 3 or more comorbidities vs no comorbidities was associated with increased disease activity.

Specifically, the presence of 2 or more cardiometabolic diseases resulted in increased disease activity (adjusted hazard ratio [aHR], 1.21; 95% CI, 1.08-1.37). The most common cardiometabolic conditions in this association were ischemic heart disease, hypertension, and cerebrovascular disease.

In addition, the presence of at least 1 psychiatric disorder was linked to an increased hazard of disease activity (aHR, 1.07; 95% CI, 1.02-1.14) — depression resulted in increased disease activity (aHR, 1.11; 95% CI, 1.03-1.20).

An increased hazard of disability worsening was observed in participants who had 2 or 3 or more comorbidities (aHR, 1.24; 95% CI, 1.11-1.39 and aHR, 1.31; 95% CI, 1.05-1.64, respectively). The researchers noted worsening of disability in participants with at least 2 cardiometabolic conditions (aHR, 1.34; 95% CI, 1.12-1.60) or at least 1 psychiatric disorder, specifically depression (aHR, 1.29; 95% CI, 1.17-1.43).

Relapse increased with greater comorbidity burden; however, cardiometabolic conditions were not associated with relapse activity, while 1 or 2 or more psychiatric disorders were associated with increased hazard of relapse (aHR, 1.15 and 1.25, respectively), especially depression (aHR, 1.21; 95% CI, 1.08-1.35).

The researchers observed a pooled proportion of 40.1% with unique active lesions, with gadolinium-enhancing lesions of 17.0% and new or enlarging lesions of 39.3%.

Sensitivity analyses showed consistency in results when including body mass index (BMI). The presence of 2 comorbidities was associated with changes in annualized disability, but not with cardiometabolic and psychiatric disorders combined and individually.

Limitations of the analysis were the lack of consistency across trials in reporting comorbidity status, as well as limited information on comorbidity severity and timing; potential unmeasured confounding owing to the study being a meta-analysis; and lack of diversity in the clinical trials.

“Our findings suggest a substantial adverse association of the comorbidities investigated with MS disease activity and that prevention and management of comorbidities should be a pressing concern in clinical practice,” the researchers concluded.