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In phase 3 clinical trials of disease-modifying therapies (DMTs) for MS, a higher burden of comorbidity were associated with worse clinical outcomes in participants. Comorbidity affected event rates in these phase 3 trials. In clinical practice, the comorbidity burden may be higher still, which makes its prevention and management even more urgent.

A recent pooled analysis, conducted by the same investigators, of comorbidities in 17 phase 3 trials showed that 25% had one, 11% had two, and 6% had three or more comorbidities¹. Consequently, Amber Salter, PhD, from the University of Texas Southwestern, and colleagues conducted a meta-analysis of data from 17 phase 3 clinical trials of DMTs, including 16,794 participants with MS. The primary outcome was time to first evidence of disease activity longer than 2 years².

Over 2 years of follow-up, 61% of participants in the pooled trials had evidence of disease activity (EDA) (61.0%; 95%CI: 56.2–66.3%; I2=97.9). Having greater than or equal to three comorbidities was associated with a 14% increased hazard of disease activity (HR 1.14; 95% CI 1.02–1.28) compared with those with no comorbidity. Patients with greater than or equal to two cardiometabolic conditions had a 21% increased hazard of disease activity (HR 1.21; 95% CI 1.08–1.37). A psychological disorder was associated with a 7% higher hazard of disease activity (HR 1.07; 95% CI 1.02–1.14). Depression and ischemic heart disease was individually associated with an increased EDA risk.

For worsening disability, having  greater than or equal to three comorbidities was associated with a 31% increase in disability worsening risk (HR 1.31; 95% CI 1.05–1.64). Patients with greater than or equal to two cardiometabolic conditions had a 34% increased risk (HR 1.34; 95% CI 1.12–1.60). Depression, ischemic heart disease, and hyperlipidemia was each associated with disability worsening. All comorbidities together as well as psychiatric comorbidities were associated with relapse risk, except for cardiometabolic diseases. Among comorbidities, no association was found with lesions on imaging.

Medical writing support was provided by Michiel Tent

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