No Evidence of Disease Progression (NEDA) seems like a clear-cut designation for patients with relapsing-remitting multiple sclerosis, but a new study suggests it isn’t always as definitive as it sounds.
A new post-analysis of a large-scale relapsing-remitting multiple sclerosis (RRMS) trial suggests a significant correlation between the number of MRI scans a physician assesses and the likelihood of a patient being told there’s no evidence of disease progression (NEDA).
The finding is based on data from the decade-old Evidence of Interferon Dose-Response European-North American Comparative Efficacy (EVIDENCE) trial. Researchers examined the study’s data and found that when doctors looked only at the 24-week MRI scan for patients enrolled in the study, they gave about 60% of patients a NEDA designation.
However, when doctors looked at several MRI scans, taken at monthly intervals, only one-third of patients were found to meet the qualifications of NEDA. Study author Patricia K. Coyle (pictured), MD, of Stony Brook University, said the findings are striking.
“It’s pretty clear that the more often you do MRI scans, the less likely you are to have patients meeting NEDA,” Coyle said. “So the number of MRI scans that you do can really have a fairly significant impact on that measurement in this analysis.”
The EVIDENCE trial was a good study to re-examine because it had a large number of patients (nearly 700) and plenty of data, Coyle said.
“This study had been done a number of years ago and several of us had been involved in the trial,” she said. “The decision was made because that was a very large study that had an interesting design of frequent MRI scans in the first couple of months and then repeating them somewhat later; there was a lot of data that could be looked at in post-hoc analysis.”
The analysis also compared rates of NEDA designation among patients in the trial who were injected with interferon beta-1a subcutaneously three times per week, versus patients who were given an intramuscular injection once weekly.
The data showed higher rates of NEDA status among patients given the subcutaneous injections, although, again, the rates in each case differed substantially depending on how many MRI scans were examined for a given patient.
Coyle said her team’s analysis ought to serve as a call for careful interpretation of NEDA data.
“What it’s really saying is that if you’re going to try to compare NEDA rates across disease modifying therapies you really need to look very carefully at the data they’re drawing from,” Coyle said.
In other words, it’s not enough to simply look at NEDA statistics; it’s important to know how those rates were determined.
“I think [NEDA] can be very valuable in formal trials as an outcome measure,” she said. “I think it begins to fall down in clinical applications in real-world settings. And I think it’s also a caution that NEDA is not the be-all and the end-all; that is has certain criticisms.”
NEDA doesn’t measure all aspects of disease progression, so it can’t be treated as if it did, Coyle said.
She said her study also underscores that fact that re-examining large trials like EVIDENCE can be a fruitful way to gain important new insights, even if the insights weren’t the original scientific endpoint.
The study, titled “Early MRI results and odds of attaining 'no evidence of disease activity' status in MS patients treated with interferon β-1a in the EVIDENCE study,” was published online in the Journal of the Neurological Sciences this month.