Clinical Outcome Measures Poster Presentation

P0059 - Defining predictors of disease activity and worsening in multiple sclerosis: an analysis of the CombiRx trial (ID 828)

  • Y. Zhang
  • Y. Zhang
  • S. Cofield
  • G. Cutter
  • S. Krieger
  • J. Wolinsky
  • F. Lublin
Presentation Number
Presentation Topic
Clinical Outcome Measures



Disease activity in multiple sclerosis (MS) is highly variable, and there are limited prospective studies on predictors of disease outcomes.


The aim of the study is to identify and assess clinical characteristics in MS that predict disease activity and progression.


The study population consisted of a prospective cohort of 1,008 patients 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 (age <38 vs. ≥38, sex, race), clinical history (number of relapses in prior year <3 vs. ≥3, disease duration, Expanded Disability Status Scale (EDSS)), and MRI metrics (presence or absence of gadolinium (Gd) and number of T2 lesions), and treatment (glatiramer acetate (GA), interferon-beta 1a (IFN), or combination therapy); with outcomes of time to first new disease activity over 7-years of follow-up including relapse, MRI activity defined by new combined unique active lesion, and disease worsening as defined by confirmed 6-month increase in EDSS.


1,008 participants were randomized, with 959 eligible for assessment of disease worsening and activity on follow-up MRI. Participants were median 38 (range 18, 61) years of age at baseline, 72.7% female, 88.3% Caucasian, 7.1% black/African American, mean 1.2 years since diagnosis, with median 2 relapses in the prior 12 months and median EDSS 2 (IQR 1, 2.5). Risk of relapse was higher in patients younger than 38 at BL vs. older (HR 1.36, 95% CI: 1.12,1.65) and with BL EDSS ≥3.5 vs. <3.5 (HR 1.66, 95% CI: 1.27, 2.14). Presence of Gd+ lesions at baseline was also associated with increased risk of relapse (HR 1.37, 95%CI: 1.14, 1.66). Risk of new MRI activity was higher in younger participants (HR 1.56, 95%CI: 1.34, 1.86) and those taking either single agent arms compared to the combination (GA: HR 1.48, 95%CI 1.22, 1.80; IFN: HR 1.43, 95%CI 1.18, 1.74). Similarly, higher preexisting lesion burden greater than the median lesion count with ≥71 T2 hyperintense lesions vs. <71 (HR 1.50, 95%CI 1.27, 1.78) and presence of BL Gd+ lesions (HR 1.75, 95%CI: 1.49, 2.06) were also associated with a higher risk of developing new MRI activity. Risk of disease worsening was higher for those with BL EDSS < 2 (HR 2.79, 95%CI 2.14, 3.67). There were no associations between sex and disease duration on clinical or radiological disease activity or worsening.


Both clinical and radiological disease activity are predicted by younger age and presence of Gd+ lesions. Additionally, relapses are also predicted by higher EDSS, and there is some protective evidence of the combination therapy in lowering risk of new MRI activity. Only baseline EDSS level was associated with disease worsening.