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A higher comorbidity burden was associated with an increased rate of AESI and early discontinuation among patients with MS in clinical trials of DMTs.

New study findings highlight the important role of comorbidities in the safety and tolerability of disease-modifying therapies (DMTs). A higher comorbidity burden was found to be associated with an increased rate of adverse events of special interest (AESI) and early discontinuation among patients with MS in clinical trials of DMTs.

Amber Salter, PhD, UT Southwestern Medical Center, Texas, presented a meta-analysis of data from individual participants of phase 3 clinical trials evaluating DMTs for MS¹. Dr. Salter and colleagues explored the association of comorbidities with safety and early discontinuation in these trials, focusing on 15 chronic conditions, most of them cardiometabolic or psychiatric. The number of comorbidities per patient was classified as 0, 1, 2, or greater than or equal to 3.

The meta-analysis included 17 clinical trials with 16,794 participants with MS. Over 2 years of follow-up, the pooled prevalence of AESI was 64% (I²=98.1). Most AESI (60.7%) were infections. Dr. Salter noted “a kind of dose-response relation” between comorbidities and AESI: as the number of comorbidities increased, so did the risk for AESI compared with those without comorbidity.

• One comorbidity: RR 1.13 (95% CI 1.09–1.17);
• Two comorbidities: RR 1.19 (95% CI 1.14–1.23); and
• Greater or equal to three comorbidities: RR 1.25 (95% CI 1.18–1.33).

A 15% increased risk for AESI was observed for study participants with greater than or equal to two cardiometabolic conditions (RR 1.15; 95% CI 1.10–1.21) and greater than or equal to two psychiatric conditions (RR 1.15; 95% 1.08–1.23). Most individual comorbidities were also associated with an increased risk for AESI. A relatively common AE in patients with MS, hyperlipidemia, was associated with a 15% higher AESI risk. The frequency of serious AEs was 3.2%. Again, having more comorbidities was associated with a higher risk for serious AEs.

The pooled early trial discontinuation was 17% (I²=97.9). A higher rate of early discontinuation was associated with having more comorbidities. The number of psychiatric disorders, but not the number of cardiometabolic disorders, was associated with an increased rate of early discontinuation.

Dr. Salter concluded: “In the broader MS community, where comorbidity burden may be higher than in this analysis, the prevention and management of comorbidities is a pressing concern.”

Medical writing support was provided by Michiel Tent.
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