A New Severity-Based Classification of MS

WASHINGTON, DC —Joseph Herbert, MD, of New York University Hospital for Joint Disease and St. Barnabas Ambulatory Care Center in Livingston, New Jersey, has developed a new severity-based classification system for multiple sclerosis (MS) that is similar to the staging system used for cancer. He presented the new system in three posters at the 21st Annual Meeting of the Consortium of Multiple Sclerosis Centers.

“In oncology practice, classification systems based on pathologic and clinical indicators of disease severity underlie the implementation of rational treatment protocols. The aggressiveness of the intervention defined by these protocols is directly linked to disease severity,” said Dr. Herbert. “Few comparable systems have been applied to MS, since historically, the disease has been classified by anatomical criteria or clinical course. These classifications are of limited therapeutic utility because they do not accurately reflect disease severity. Identification of subpopulations based on disease severity would enable more homogeneous stratification for purposes of treatment and clinical trial design.”

The classification system that Dr. Herbert developed consists of a spectrum ranging from “benign MS” at one end to “malignant MS” at the other, with six subgroups in between. The percentile of the patient’s score on the Multiple Sclerosis Severity Scale (MSSS) determines the grade. The MSSS, published by Roxburgh et al in Neurology in 2005, takes into account both the Expanded Disability Status Scale (EDSS) rating and the duration of disease to arrive at a score ranging from 0.01 to 9.99. “Any measure of disease severity must comprise a component of disease duration, in order to assess rate of change,” wrote Dr. Herbert. Disease duration is determined by time since the patient’s first symptom—not time since diagnosis.

Dr. Herbert redefined “benign MS” on the premise that definitions—and therefore, reported prevalence of this diagnosis—have been inconsistent in the medical literature. He said it was important to distinguish between benign MS, which may not require treatment since it is not expected to progress over time, and mild MS, which may benefit from early immune-modulating therapy to slow worsening over time. His classification system defines benign MS as an MSSS score of 0.45 or less, which translated into an EDSS score of less than 2.0 after 30 years’ duration. This should be distinguished from mild MS, which he defines as an MSSS score of less than 1.7, which corresponds to an EDSS score of less than 4.0 after 30 years.

On the other end of the spectrum, “malignant MS” can be defined as an MSSS score of 9.59 or higher, corresponding to an EDSS score of 6.0 at 2 years, 7.0 at 5 years, and 8.0 at 10 years, according to Dr. Herbert. Malignant MS is a subset of aggressive MS, which Dr. Herbert defined as an MSSS score of 8.24 or higher, corresponding to an EDSS score of 4.0 at 2.5 years, 6.0 at 7 years, and 7.5 at 18 years.

To arrive at the boundaries for the other classifications, Dr. Herbert began by dividing the population in half at the 50th percentile (MSSS score, 5.0), so “those patients with disease less severe than the median become separated from those with more severe disease.” He then further divided the population at the 34th and 67th percentiles resulting in the six subpopulations, which he rated as mild, moderate, intermediate, advanced, accelerated, and aggressive MS.

“This new classification system presents several advantages over the current system, which is purely descriptive of disease course,” wrote Dr. Herbert. He stated the major advantage of MSSS scores is that they are “based on a single, cross-sectional measurement of the EDSS, provided disease duration is known.” He further noted that the MSSS is more powerful than the EDSS alone in detecting progression of disability and that it is more sensitive to changes in short disease duration and low EDSS score. Dr. Herbert’s posters include the caveat “Caution should be exercised in attempting to predict disease course in individual patients using the MSSS scoring system. Stability of MSSS over time is applicable to patient groups within a given decile, not in individual patients.” In addition, definitions cannot be applied within the first year of diagnosis, since “only MSSS scores assigned after the first year are representative of overall disease severity over time.”

Dr. Herbert concluded, “The ultimate goal of disease severity stratification systems such as this is to facilitate the development of more rational treatment protocols for patients with MS, where treatment selection is aligned with disease severity and clinical trial design.” For example, more aggressive treatment may be considered for patients with a more aggressive disease classification. Furthermore, Dr. Herbert suggested that pivotal trials be reanalyzed with stratification according to MSSS group, since this “may yield more robust changes than previously appreciated.” Finally, he noted that in the future, the classification system might be further modified to include biochemical or radiologic criteria, once these have been defined.          

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