Predictive value of NEDA and brain atrophy in MS


REPORT FROM ECTRIMS – BARCELONA, SPAIN – OCTOBER 7-10, 2015 – A recent longitudinal study investigated whether MS patients with ongoing disease activity while on treatment had different clinical, radiological and neuropsychological outcomes at one year compared to those with no evidence of disease activity (NEDA), defined as no relapses, no three-month EDSS progression and no new MRI activity (Nygaard et al. PLoS One 2015;10:e0135974; free full text at

Overall, 46% of treated MS patients had evidence of disease activity and demonstrated EDSS progression (+0.4 points). In contrast, NEDA patients showed a slight improvement in EDSS scores (-0.3 points), which may be due to an absence of relapse-related short-term disability. Cognitive function was stable in both groups but patients with disease activity had a significantly higher rate of subcortical grey-matter (GM) atrophy compared to healthy controls.

Also important to long-term outcomes is the rate of brain volume loss, which is significantly higher in MS patients compared to age-matched controls. Accordingly, several authors have suggested a combined metric of NEDA + atrophy (NEDA-4) for predicting disability progression. The proposed cut-off value for percent brain volume change (PBVC) is -0.4%/year, which is roughly the atrophy rate that distinguishes MS from healthy controls (De Stefano et al. J Neurol Neurosurg Psychiatry 2015; epublished April 22, 2015; free full text at

The predictive value of NEDA and NEDA-4 at six-year follow-up was examined in a post-hoc analysis of data from the FREEDOMS and FREEDOMS II trials and extensions of fingolimod (Kappos et al. ECTRIMS 2015; abstract 570). Patients who did not achieve NEDA in year 1 of treatment were significantly more likely to have a relapse (hazard ratio 2.16), six-month confirmed disability progression (HR 1.79), either relapse or disability progression (HR 1.79), or to reach EDSS 6.0 (HR 1.60) at six-year follow-up.

Similarly, patients who did not achieve NEDA-4 in the first year of treatment were at significantly higher risk of relapse (HR 1.81), disability progression (HR 1.61), either relapse or disability progression (HR 1.72) or to reach EDSS 6.0 (HR 2.85). Failing to achieve NEDA-4 was also associated with a significantly higher risk of annual brain volume loss >0.4% (HR 2.94). The authors concluded that NEDA appears to correlate more with relapses and focal inflammation, whereas NEDA-4 is a better predictor of brain volume loss and long-term disability outcomes.

A separate analysis of FREEDOMS/FREEDOMS II data reported that fingolimod-treated patients were four-fold more likely to achieve NEDA-4 compared to those on placebo (odds ratio 4.41) (Freedman et al. ECTRIMS 2015; abstract P626). The likelihood of NEDA-4 was higher in patients aged < 30 years (OR 6.37), >2 relapses in the prior two years (OR 5.48), and baseline EDSS score >3.5 (OR 8.20), suggesting that younger patients and those with significant disease activity would obtain the most benefit from therapy. Odds ratios were similar for females and males (4.25, 4.80).

Reviewer: Dr. Daniel Selchen, Head of Neurology, St. Michael’s Hospital, Toronto, Canada

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