Three early clinical factors have been identified that predict a high risk of developing aggressive disease in people with multiple sclerosis.

Older age at symptom onset, greater disability  in the first year since symptom onset, and the presence of pyramidal signs are associated with reaching an Expanded Disability Status Score (EDSS) ≥6 within 10 years of symptom onset, according to a new study.

And conversely, the absence of any of these factors is associated with a much lower risk of aggressive disease compared to the general multiple sclerosis population, the review led by Australian researchers has found.

In real world use, these factors could be applied to identify patients who would benefit from early intervention, with disease modifying therapies for MS, according to the analysis led by Dr Charles Malpas of the CORe Unit, at the University of Melbourne.

“For ease of clinical implementation, these criteria can be defined as: median EDSS ≥3, any pyramidal signs on examination in the first year, and age >35 at symptom onset,” they write in the journal Brain.

Their study analysed data from 2403 patients in the international MSBase registry who had 10 years of follow up on EDSS scores, of whom 145 patients (6%) were classified as having aggressive multiple sclerosis (6%). The three clinical factors significantly predicted aggressive multiple sclerosis with an AUC of 0.80, positive predictive value of 0.15 and negative predictive value of 0.98.

The presence of all three signs was strongly predictive, with 32% of such patients meeting aggressive disease criteria. The absence of all three signs was associated with a 1.4% risk. And the predictive value of the three factors was confirmed in an analysis of a  Swedish Multiple Sclerosis Registry cohort.

The researchers said the findings could help provide  “objective guidance for treatment of potentially aggressive disease at early disease stages in a condition whose management revolves around effective prevention disability driven by episodes of CNS inflammation.”

“Identifying patients who are at a high risk of developing an aggressive multiple sclerosis is of high clinical importance,” they said.

“Previously, we have demonstrated that choice of a second-line therapy, in particular early in the disease course, has the capacity to prevent or delay development of the secondary progressive multiple sclerosis form and mitigate the evolution of neurological disability.”

The next step in research will be to determine whether aggressive multiple sclerosis can be prevented by the use of aggressive treatment strategies in patients who are predicted to develop aggressive disease, they concluded.