Association of Age With Contrast-Enhancing Lesions Across the Multiple Sclerosis Disease Spectrum

Background and ObjectivesTo investigate the association of age and the presence of contrast-enhancing lesions (CELs) on cranial MRI scans in different disease courses of multiple sclerosis (MS), we describe the frequency of CELs as a function of age in 4 large randomized controlled trial (RCT) datasets.MethodsUsing original trial data from CombiRx (Combination Therapy in Patients With Relapsing-Remitting Multiple Sclerosis; clinicaltrials.gov identifier NCT00211887), a trial in relapsing-remitting MS; ASCEND (A Clinical Study of the Efficacy of Natalizumab on Reducing Disability Progression in Participants With Secondary Progressive Multiple Sclerosis; clinicaltrials.gov identifier NCT01416181), a trial in secondary progressive MS; and the 2 primary progressive MS trials PROMISE and INFORMS; clinicaltrials.gov identifier NCT00731692), we describe the occurrence of CELs per age group at baseline for the entire trial cohort and at 1 year follow-up in the treatment arms.ResultsCombiRx included 1,008, ASCEND 889, PROMISE 943, and INFORMS 970 participants. At baseline, CEL frequency differed between datasets according to disease course: 39.6% of CombiRx, 23.9% of ASCEND, 14.0% of PROMISE, and 12.3% of INFORMS participants had CELs. This distribution by disease course was largely preserved within each age group. In all datasets, there was an almost linear decrease of the percentage of participants with CELs with advancing age. After 1 year of experimental treatment, CEL occurrence was reduced in all trial datasets, and almost absent in ASCEND. The decrease of CEL occurrence with advancing age was preserved in CombiRx, PROMISE, and INFORMS after 1 year of treatment. We investigated the association of the baseline factors age, disease duration, sex, and EDSS with having CELs at baseline with multivariable binary logistic regression models. Age was the only characteristic associated with the risk of CELs at baseline in all datasets, with higher age associated with a lower risk of CELs (odds ratios for having CELs at baseline per year increase in age: CombiRx: 0.96, 95% confidence interval [CI] 0.95-0.98; ASCEND: 0.94, 95% CI 0.92-0.97; PROMISE: 0.94, 95% CI 0.91-0.96; INFORMS: 0.97, 95% CI 0.94-0.99).DiscussionOur analysis of 4 large, well-characterized RCT datasets shows that the association of age and CEL occurrence is a general phenomenon across the spectrum of MS disease courses. Our findings should be replicated in real-world MS datasets.