Comorbidities linked to early discontinuation of disease-modifying therapy trials for MS

Key takeaways:

• Greater comorbidity burden was associated with a higher rate of adverse events.
• Patients with comorbidities were more likely to discontinue trials early than those with none.

WEST PALM BEACH, Fla. — A higher comorbidity burden was linked to an increased rate of adverse events as well as early discontinuation among patients with MS who participated in phase 3 clinical trials of disease-modifying therapies, data show.

“Comorbidities are common in persons with MS, but comorbidity status is not generally reported in [disease-modifying therapy (DMT)] trials,” Amber Salter, PhD, associate professor of biostatistics in the department of neurology at UT Southwestern Medical Center, told Healio regarding the research presented at ACTRIMS. “Additionally, observational studies have shown associations with early DMT discontinuation in persons with comorbidity.”

Salter and colleagues conducted a two-stage meta-analysis of 17 phase 3 clinical trials evaluating DMTs in 16,794 individuals with MS who were followed for at least 2 years.

The individual comorbidities that the researchers assessed included autoimmune conditions, cerebrovascular disease, diabetes, functional heart conditions, hyperlipidemia, hypertension, ischemic heart disease, lung and skin conditions, migraine, peripheral vascular disease, depression, anxiety and other psychiatric disorders.

Overall, 64% of patients had a specific adverse event of interest (AESI), most of which were infections.

The researchers reported that greater comorbidity burden was associated with a higher rate of AESI, including for patients with one comorbidity (RR = 1.13; 95% CI, 1.09-1.17), two comorbidities (RR = 1.19; 95% CI, 1.14-1.23) and three or more comorbidities (RR = 1.25; 95% CI, 1.18-1.33) compared with those who had no comorbidities. This included a 15% increased risk for AESIs among those with two or more cardiometabolic conditions and two or more psychiatric conditions.

Salter and colleagues additionally found that 17% (95% CI, 13.8%-20.9%) of participants discontinued a DMT trial early. The rate of early discontinuation was higher in those with two comorbidities (RR = 1.23; 95% CI, 1.07-1.42) and three or more comorbidities (RR = 1.19; 95% CI, 1.01-1.4) vs. those with no comorbidities. This association was particularly notable for psychiatric disorders, according to the researchers.

“While our study findings warrant further study in the broader MS population, the net benefit of treatment in those with comorbidity should be considered in clinical decision-making,” Salter told Healio. “Also, patients with comorbidity in clinical practice may need additional support to prevent early discontinuation of disease modifying therapies.”