Nov 05, 2009
Society-Funded Researchers Show that Early Relapses Link to MS Progression
A group funded by the National MS Society reports that more relapses early in the course of MS were associated with increased disease progression in a study of 2,477 people with MS, but that this effect diminishes over time. Helen Tremlett, PhD, and colleagues (University of British Columbia, Vancouver) report these results in Neurology (2009;73:1616-23).
Background: The course of MS can involve both relapses – exacerbations or flare-ups that involve new symptoms or worsening of old symptoms – and disease progression (persistent worsening of neurologic symptoms, and development of sustained disability). Although we have some clues, we don’t yet fully understand what triggers relapses or what causes MS to progress. The disease progression rate, severity, and specific symptoms of MS are unpredictable and vary from one person to another. In light of these uncertainties, Dr. Tremlett aimed to study the impact of both early and later disease relapses on disease progression over time.
The Study: Dr. Tremlett’s team retrospectively reviewed the histories of 2,477 people with MS selected from the British Columbia MS database. Cases were included if MS had a relapsing onset (as opposed to immediately progressive) and if diagnosis occurred before July 1988. The cases had been followed for an average of 20.6 years.
The group looked at the impact of relapses at different time periods on disease progression, which for this study was defined as progression to an EDSS score of 6 or the onset of secondary-progressive phase of disease. (The EDSS is a scale that measures MS disease severity. A score of 6 is assigned when the individual requires the use of a cane for walking. Secondary-progressive MS is a course of steadily worsening disease with or without occasional flare-ups, which often follows an initial period of relapsing-remitting MS.)
They focused on the relationship between relapses during the first five years of MS, years 5 to 10, and after more than 10 years, and progression. People who had more relapses within the first five years of disease were more likely to reach an EDSS of 6. Relapses during this period had the most impact on early disease progression. However the association between early relapses and progression decreased over time, so that people with early relapses who did not experience significant progression early in the course of their disease (did not require a cane to walk by year 10 or did not transition to secondary-progressive disease) were only slightly more likely to at longer-term follow-up.
Dr. Tremlett also found that relapses in people under the age of 25 had a more enduring impact on disability compared to those 35 years of age and older. This underscores the importance of early treatment to prevent relapses and hopefully, future disability.
Comment: In an accompanying editorial, Ruth Ann Marrie, PhD (University of Manitoba, Winnipeg, Canada) and Gary Cutter, PhD (University of Alabama, Birmingham) comment that teasing out the role of relapses is important because disease-modifying drugs that are approved to treat MS clearly reduce relapse frequency but have shown only moderate effects on disability progression in the limited duration of most clinical trials. However, they caution against underestimating the role of relapses, despite the fact that Dr. Tremlett’s team found a diminishing effect of relapses on disability progression over time.
“The financial cost of a single severe relapse is estimated at more than $10,000,” write Drs. Marrie and Cutter. “The emotional costs—including anxiety and anger—and social costs are also high. While moderate or severe gait dysfunction is inherently important and more easily measured than other domains, domains such as vision, cognition, and hand function are also important.”
More research is needed to understand the full effects of relapses on disability progression, and how disease-modifying drugs impact the long-term course of MS.
Read more about coping with exacerbations and progression in MS.