BARCELONA—Neurologists can predict outcomes in patients with relapsing-remitting multiple sclerosis (MS) more accurately by adopting an expanded conception of no evidence of disease activity (NEDA), according to data presented at the 31st Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS). In addition to relapses, disability progression, and MRI activity, NEDA-4 includes change in brain volume over time. A patient’s NEDA-4 status at one year has advantages over the conventional NEDA-3 for predicting subsequent disability and structural damage for as long as seven years. NEDA-3 status at one year, however, is more closely correlated with relapses and new or enlarging T2 lesions than NEDA-4 status is.
Achieving NEDA reduces the probability of subsequent clinical and MRI disease activity. “These findings support the use of NEDA-4 as a more comprehensive and balanced measure for predicting long-term disease evolution in relapsing MS,” said Ludwig Kappos, MD, Chair of Neurology at University Hospital in Basel, Switzerland. “The finding needs further confirmation with longer follow-up and also other groups of patients.”
Ludwig Kappos, MD
An Analysis of FREEDOMS Data
Dr. Kappos and colleagues examined data from the FREEDOMS extension studies, which compared fingolimod with placebo, to determine whether adding brain-volume change to NEDA-3 improved the latter’s predictive value. The disease outcomes that the researchers chose to study were confirmed relapse, new or enlarging T2 lesions on MRI, six-month confirmed disability progression, confirmed Expanded Disability Status Scale (EDSS) score of 6 or greater, and mean annual brain volume loss. Dr. Kappos and colleagues examined participants’ NEDA-4 and NEDA-3 statuses after one year of observation and after two years of observation. They analyzed the data with Cox regression analysis and the Akaike information criterion to evaluate the respective predictive values of NEDA-4 and NEDA-3.
The investigators found that NEDA-4 status at one year and NEDA-3 status at one year predicted time to first relapse, although NEDA-3 status was associated with a higher hazard ratio of first relapse than NEDA-4 was. Similarly, NEDA-4 status at one year and NEDA-3 status at one year predicted time to new T2 lesion activity, but NEDA-3 predicted this outcome slightly better than NEDA-4 did. NEDA-3 status was associated with a hazard ratio of 1.4 for six-month confirmed disability progression, and NEDA-4 was associated with a 1.6 hazard ratio for this outcome.
Few participants reached an EDSS of 6 or greater, which was the most stringent and perhaps the most clinically relevant criterion of the study, said Dr. Kappos. Failure to achieve NEDA-3 at one year increased the risk of this outcome by a hazard ratio of 1.6, and failure to achieve NEDA-4 at one year increased the risk of this outcome by a hazard ratio of 2.8. Likewise, failure to achieve NEDA-4 at one year was more closely correlated with continuous brain volume loss over the observation period than failure to achieve NEDA-3 at one year was.
Imaging Affects NEDA’s Predictive Value
The investigators obtained similar results when they examined patients’ NEDA-4 and NEDA-3 status at two years. NEDA-4 status at two years predicted brain volume change and attainment of an EDSS score of 6 or greater with more accuracy than did NEDA-3 status at two years. NEDA-3 status at two years had advantages over NEDA-4 status at two years for predicting new and enhancing lesions and confirmed relapses. Both methods of statistical analysis indicated similar conclusions.
Dr. Kappos acknowledged that MRI in the clinical setting has not been standardized. This lack of uniformity may affect the relative predictive value of new and enlarging T2 lesions, compared with gadolinium enhancement, which is more easily detected in nonstandardized scans, he added. The measurement of brain volume change depends to an even greater extent on a stringent methodology of the assessments and high-quality scans.
—Erik Greb