Anxiety and Depression Linked to RRMS Relapse Risk, Study Finds

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by Steve Bryson, PhD |

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Comorbidities such as anxiety and depression are associated with a significantly increased risk of relapse in people with relapsing-remitting multiple sclerosis (RRMS), a clinical trial analysis has found. 

Anxiety and abnormal blood lipids (fats) also increased the risk of any RRMS disease activity. 

Based on those findings, researchers suggest that the presence of comorbidities (coexisting conditions) may influence clinical trial outcomes and should be investigated.

The study, “Comorbidity is associated with disease activity in MS: Findings from the CombiRx trial,” was published in the journal Neurology

Many people with MS have chronic comorbidities, with the most common ones being depression, high blood pressure (hypertension), anxiety, and abnormal blood lipid levels. 

While studies suggest that comorbidity may influence the severity of disease at diagnosis, as well as the rate of disease worsening, little is known about the impact of comorbidity on measures of disease activity such as relapse rate. 

Researchers based in the U.S. and Canada conducted a study to assess the prevalence of comorbidities in RRMS patients and explore the possible association between comorbidity and clinical measures such as relapses, disability worsening, and the presence of active lesions as determined by MRI scans. 

For this analysis, data were obtained from the CombiRx Phase 3 clinical trial (NCT00211887), which compared the combination of interferon beta-1a (marketed as Avonex by Biogen) and glatiramer acetate (marketed as Copaxone by Teva Pharmaceuticals) to each of these agents alone (monotherapy), versus placebo in treatment naïve RRMS patients. 

At enrollment, patients underwent clinical tests to determine their expanded disability status scale (EDSS) score, followed by additional assessments every three months for 36 months, then every six months after. MRIs were completed at enrollment and six, 12, 24, and 36 months, then yearly.

The team assessed comorbidities particularly related to MS, such as hypertension, abnormal blood lipids, diabetes, depression, anxiety, and migraine headaches. 

The primary outcome for the analysis was the time to first evidence of disease activity — defined as relapses, disability worsening, or MRI changes.

Of the 959 participants (mean age of 37.9 at baseline) selected from the CombiRx trial, more than half (55.1%) had at least one comorbidity at enrollment and roughly two-thirds were considered overweight or obese.

Throughout the follow-up period — median length of 3.4 years (range 0.5 to 6.9 years) — the prevalence of each comorbidity and the number of comorbidities increased over time. Participants with more comorbidities were more likely to be overweight or obese.

The prevalence and number of comorbidities did not differ between Avonex and Copaxone treatment groups, neither at enrollment nor over the follow-up period. 

However, some significant differences in the prevalence of individual comorbidities were found according to the patient’s age and sex.

The median disability level was lower for those without comorbidities compared to those with two or more (after adjusting for disease duration), and for those with more than three comorbidities (after adjusting for age). 

Overall, 739 (77.1%) of participants had evidence of disease activity based on relapses, EDSS worsening, or MRI lesion activity. 

After adjusting the data for age, sex, race, body mass index, and treatment, an increased risk of any disease activity was found to be significantly associated with anxiety (25% increased risk) and abnormal blood lipids (32% increased risk). Migraines were associated with a lower risk of any disease activity (20% decreased risk). 

The number of comorbidities was not related to the time until any disease activity event. 

Anxiety was significantly linked to an increased risk of relapses, even after adjustments were made for the possibility that relapses may trigger anxiety. Depression also was associated with an increased risk of relapse. As the number of comorbidities increased, an increased risk of relapses was observed.

No significant associations were found between any comorbidity and disability worsening or lesion activity. The addition of smoking status (ever or never) to the statistical analysis did not change most of the main findings. 

“In this large trial population with rigorously obtained outcomes, comorbidities were common among participants and influenced disease outcomes, including relapses,” the researchers wrote, noting that “the comorbidity burden of clinical trial participants with MS may be an important factor in the outcome of clinical trials.”

“Additional investigations of the impact of comorbidity on clinical trial outcomes, and response to disease-modifying therapies is warranted,” they added. 

According to the National MS Society, in an accompanying editorial Lorene M. Nelson, PhD, and Dennis Bourdette, MD, emphasized that “treating persons with MS should not just be about choosing a DMT to prevent disease progression. Neurologists need to treat the whole patient.”

The society noted that comorbidities are often modifiable through wellness interventions — including increasing physical activity, managing weight, reducing stress — and addressing them may contribute to improve the overall health status of MS patients, and reduce the risk of disease worsening.