Abstract
Background and Objectives: Disease activity in multiple sclerosis (MS) is highly variable, and there are limited prospective studies on predictors of disease outcomes. The goal of the study is to identify and assess patient characteristics in MS that predict disease activity and worsening.
Methods: The study population consisted of a prospective cohort of 1,008 participants with relapsing-remitting (RR) onset MS enrolled in the CombiRx trial. Cox regression analysis was used to determine hazard ratio (HR) associations between baseline (BL) demographics, clinical history, MRI metrics, and treatment; with outcomes of time to first new disease activity over up to 7-years of follow-up including relapse, MRI activity, and disease worsening.
Results: 1,008 participants were randomized, with 959 eligible for assessment of disease activity and worsening on follow-up. In the multivariable models, risk of relapse was higher in participants younger than 38 at BL vs. older (HR range 1.36-1.43), with presence of Gd+ lesions at baseline (HR 1.38, [95%CI: 1.14, 1.67]), and with BL EDSS ≥3.5 vs. <3.5 (HR range 1.63-1.67). Risk of new MRI activity was higher in younger participants (HR range 1.58-1.84), with higher preexisting lesion counts greater than the median lesion count with ≥71 T2 hyperintense lesions vs. <71 (HR 1.50, [95%CI 1.27, 1.77]), with presence of BL Gd+ lesions (HR 1.75, [95%CI: 1.49, 2.06]), and higher baseline T2 lesion volume (HR 1.02 for every unit increase in baseline volume, [95% CI 1.01, 1.03]). Risk of new MRI activity was lower in those receiving combination therapy compared to either GA (HR range 0.67-0.68) or IFN (HR range 0.68-0.70). Risk of disease worsening was higher for those with higher T2 volume (HR for 1 unit increase in volume 1.01, 95% CI 1.004, 1.03) and BL EDSS <2 (HR range 2.79-2.96). There were no associations between sex, race, and disease duration on relapse, MRI activity, or disease worsening in multivariable analysis.
Conclusion: Prospective data from a large clinical trial cohort shows that younger MS patients with high baseline relapses and MRI lesion burden have the highest risk of subsequent disease activity.
CombiRx was registered at ClinicalTrials.gov (NCT00211887) on September 21, 2005. Study enrollment began in January 2005.
Footnotes
Clinical Trial registration number: NCT00211887
- Received December 13, 2021.
- Accepted April 11, 2022.
- © 2022 American Academy of Neurology
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