June 26, 2014

Early Relapses, Onset of Progression, and Late Outcome in MS

A team of researchers from England and Germany investigated the relationship between early relapses (within the first 2 years), secondary progression (SP), and late disability in MS. They suggest that the total number of early relapses in the relapsing-remitting phase does not influence the time to secondary progressive onset. [Antonio Scalfari, MD; Anneke Neuhaus, MSc; Martin Daumer, PhD; Gabriele C. DeLuca, MD, PhD; Paolo A. Muraro, MD, PhD; George C. Ebers, MD. Arch Neurol. 2012; doi:10.1001/jamaneurol.2013.599. Online First]

The Study: Supported in part by the MS Society of Canada, a research team from the Imperial College London and University of Oxford, England and Sylvia Lawry Centre for Multiple Sclerosis Research, Germany investigated the relationship between early relapses in the first 2 years of onset, secondary progression, and late disability.  Data from 730 patient records of people with relapsing-remitting MS from the London Multiple Sclerosis Clinic in Ontario were used, covering a 28-year period between 1972 and 2000. Disability was scored using the EDSS (Expanded Disability Status Scale) and none of the people had received disease-modifying therapies. The following areas were examined:

  • High frequency early relapses — A total of 158 people in the study group experienced frequent early relapses (>3 relapses within the first two years of the disease). Of the frequent early relapse group, 79 people converted to SP at 9 years after onset and by 24 years from onset, 103 had converted to SP. The remaining 55 people did not enter the SP phase despite experiencing frequent early relapses.

  • Time to onset of SP and disability prognosis For those without secondary progression (SP) , the probability of requiring a mobility aid was reduced by 24% after 5 years , by 42% after 10 years  and 56% after 15 years of  disease.  Conversely, a shorter duration of the relapsing-remitting phase, meaning the early development of secondary progression, was associated with reaching disability milestones such as 6.0 or 8.0 much faster. Those with a longer time to the SP phase (≥13 years) attained an EDSS score of 6.0 on average 11.9 years later than those with a shorter time to the development of the SP (1-5 years) phase.

  • Early relapses and length of time to progression — The probability of developing early advanced disability was shown to increase proportionally to the number of early relapses (up to 3 relapses within the first two years) only in people who had a shorter relapsing-remitting phase before conversion to SP disease.  What seemed most important regarding early disability development was the early appearance of SP disease.

At the end of the study period, disease outcomes varied a great deal within the group who initially presented with frequent early relapses. These findings indicate a lack of association between early clinical activity (relapses) and the onset of SP disease and further question using relapse frequency alone as a valid predictor for the early development of disability. Additional research in this area is warranted.