COPENHAGEN—Dysfunction within the pyramidal system may be the strongest independent clinical predictor of disability progression in patients with clinically isolated syndrome (CIS), according to research presented at the 29th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS). Older age at CIS onset, however, may be a poor prognostic indicator. Factors that predict disability progression in patients with relapsing-remitting MS may also predict the same outcome in patients with CIS.
Natural history studies indicate that high T2 lesion burden is a poor prognostic indicator, but “in our study, this [finding] is confounded by treatment,” said Vilija Jokubaitis, PhD, researcher in the Department of Medicine at the University of Melbourne. Dr. Jokubaitis and colleagues found that high T2 lesion load was associated with earlier and longer treatment exposure.
The researchers also observed that exposure to disease-modifying therapies (DMTs) significantly delayed the accumulation of disability. The investigators found an association between increase in treatment exposure and a decrease in the hazard of progression. “Our data suggest that the early and consistent use of DMTs is key in delaying the accumulation of MS-related disability,” said Dr. Jokubaitis.
Monitoring for Disability Progression
Dr. Jokubaitis and colleagues analyzed data from the MSBase Incidence Study, an investigator-initiated, prospective, observational cohort study of patients with CIS. The study began collecting data in 17 countries in 2004. Persons who had been diagnosed with CIS within 12 months of onset were enrolled into this study.
At baseline, the researchers collected demographic information, Expanded Disability Status Scale (EDSS) scores, Kurtzke functional scores (KFS), and cerebral MRI. Baseline MRI scans were available for 89% of the patients. At follow-up, the investigators collected EDSS scores, KFS, relapse information, and information about changes in treatments. The study’s primary end point was disability progression events, which were defined as an EDSS score increase of at least one point above a minimum baseline EDSS score of 1. The increase had to be maintained for a particular period of time. The study focused on disability progression events at three months and at 12 months.
A total of 1,989 patients had at least three EDSS scores spanning a minimum of nine months. Of these patients, 391 had a three-month confirmed disability progression event, and the event was maintained for at least 12 months in 307 patients.
First-Line Drugs Had Equivalent Efficacy
Approximately 71% of patients were female. Patients’ average age at CIS onset was 33, and their median EDSS score at baseline was 1.5. About 9% of patients had fewer than three T2 lesions on cerebral MRI.
Hazard regression analysis indicated that every 10 years of age were associated with a 1.17 increase in the hazard of disease progression. A KFS of 2 or greater was associated with roughly a 1.5-fold increase in the risk of disability progression, compared with patients who had a pyramidal KFS of 0 or 1.
To assess the effect of treatment, the researchers compared patients who were treated before the accumulation of disability with patients who were untreated before the accumulation of disability. All first-line injectable drugs decreased patients’ risk of progression by approximately 50%.
—Erik Greb
Senior Associate Editor