After Stabilizing Treatment, Disease Activity Predicts Outcome in Study

Assessing disease activity from the first to second year after a diagnosis of multiple sclerosis (MS), once treatment has been initiated and stabilized, can help predict long-term disability outcomes.

That’s according to the study, “Rebaseline no evidence of disease activity (NEDA-3) as a predictor of long-term disease course in a Norwegian multiple sclerosis population,” published in Frontiers in Neurology.

No evidence of disease activity based on three components, or NEDA-3, means someone with MS hasn’t had any relapses, disability progression, or new inflammatory activity on MRI scans. NEDA-3 is frequently used as an outcome measure in studies, but debate about how well short-term results can predict long-term disability outcomes continues.

Scientists in Norway retrospectively analyzed 536 people diagnosed with MS between 2006 and 2017 who were followed for at least a year. Among them, 38% (202 patients) achieved NEDA-3 a year after being diagnosed.

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Disease activity after diagnosis, at ‘re-baseline’

On average, it took these patients 33.8 years to reach a score of 6 on the expanded disability status scale (EDSS), meaning patients require an aid such as a cane or crutch to walk short distances. The average time to an EDSS score of 6 was 30.8 years for those who didn’t achieve NEDA-3 after the first year, a statistically significant difference.

In a separate analysis, the researchers looked at data of 446 patients who’d been followed for at least two years, specifically at “re-baselined” NEDA-3, assessing disease activity from one year after diagnosis. The rationale for this analysis is that treatment regimes are being started and adjusted in the first year after diagnosis, so treatments are usually stabilized after a year. Looking at disease activity in the second year might be more informative of long-term outcomes, the researchers reasoned.

“Disease modifying therapies do not reach full clinical efficacy until after several weeks to months, and NEDA must be adapted accordingly when utilized as an outcome measure,” they wrote.

In the re-baselined analysis, 52% of the patients achieved NEDA-3.

“Although there was no increase over time in the proportion of pwMS [people with MS] achieving NEDA in year one, there was an increase over time in the proportion of pwMS achieving NEDA when rebaselining, suggesting we are getting better at stabilizing the disease early,” the researchers wrote.

The average time to EDSS 6 was significantly longer, by nearly 15 years on average, for patients who achieved NEDA-3 in the re-baselined analysis — 44.5 years in those achieving NEDA-3 vs. 29.6 years among those not achieving NEDA.

“NEDA-3 from rebaseline after 1 year, once treatment is stabilized, can predict the long-term disease course in MS,” the researchers wrote.

NEDA-3 and high-efficacy DMT

Those treated initially with high-efficacy disease-modifying therapies (DMTs) — namely Lemtrada (alemtuzumab), Gilenya (fingolimod), or Tysabri (natalizumab) — were more likely to achieve long-term NEDA-3 than those who started on moderate-efficacy therapies, specifically Copaxone (glatiramer acetate), Aubagio (teriflunomide), Tecfidera (dimethyl fumarate), or interferon therapies, analyses indicated.

“Starting a high efficacy DMT is associated with longer time to NEDA failure than starting moderate therapies,” the researchers wrote, adding the result “supports the importance of early diagnosis and high efficacy therapy early in the disease course to prevent long-term disability.”

Among patients who achieved NEDA-3 after re-baselining, the average time to NEDA-3 fail was about 4.8 years for those receiving high-efficacy DMTs vs. 3.1 years in those receiving moderate-efficacy therapies.

Most patients with NEDA-3 failure had failed to achieve one of the three indicators of disease activity included in the score, most commonly new MRI activity, analyses also showed.

“New MRI lesions were the most common cause of NEDA failure (63%), followed by new relapses (50%) and EDSS change (25%),” the researchers wrote.