A comprehensive meta-analysis of multiple sclerosis clinical trials has revealed that patients with concurrent medical conditions face increased challenges in completing disease-modifying therapy (DMT) studies, highlighting the need for more tailored approaches in clinical trial design and patient support.
Impact of Comorbidity Burden on Trial Outcomes
The two-stage meta-analysis, presented at ACTRIMS and led by Dr. Amber Salter from UT Southwestern Medical Center, examined 17 phase 3 clinical trials involving 16,794 MS patients over a minimum two-year follow-up period. The findings demonstrated a clear correlation between comorbidity burden and adverse events, with risk increasing proportionally to the number of concurrent conditions.
Patients with single comorbidity showed a 13% higher risk of adverse events (RR = 1.13; 95% CI, 1.09-1.17), while those with two comorbidities faced a 19% increase (RR = 1.19; 95% CI, 1.14-1.23). The risk escalated further for patients with three or more comorbidities, reaching 25% (RR = 1.25; 95% CI, 1.18-1.33).
Early Discontinuation Patterns
The study revealed a concerning trend in trial completion rates, with approximately 17% of participants discontinuing DMT trials prematurely. Patients with two comorbidities showed a 23% higher likelihood of early discontinuation (RR = 1.23; 95% CI, 1.07-1.42), while those with three or more comorbidities had a 19% increased risk (RR = 1.19; 95% CI, 1.01-1.4).
Specific Comorbidity Impacts
The research team evaluated various comorbidities, including:
- Autoimmune conditions
- Cerebrovascular disease
- Diabetes
- Cardiovascular conditions
- Psychiatric disorders
- Respiratory and dermatological conditions
Notably, patients with multiple cardiometabolic or psychiatric conditions showed a 15% increased risk for adverse events of special interest (AESI), with infections being the predominant concern.
Clinical Implications
"Comorbidities are common in persons with MS, but comorbidity status is not generally reported in DMT trials," noted Dr. Salter. This observation underscores a significant gap in current trial protocols and reporting practices.
The findings suggest that healthcare providers should carefully consider the net benefit of treatments for patients with comorbidities and potentially implement additional support systems to prevent early discontinuation of disease-modifying therapies. These results also highlight the importance of comprehensive patient assessment and individualized treatment approaches in MS management.
