Rotstein DL, Healy BC, Malik MT, Chitnis T, Weiner HL. Evaluation of no evidence of disease activity in a 7-year longitudinal multiple sclerosis cohort. JAMA Neurol. 2015 Feb;72(2):152-8


With multiple and increasingly effective therapies for relapsing forms of multiple sclerosis (MS), disease-free status or no evidence of disease activity (NEDA) has become a treatment goal and a new outcome measure. However, the persistence of NEDA over time and its predictive power for long-term prognosis are unknown.


To investigate NEDA during 7 years as measured by relapses, disability progression, and yearly magnetic resonance imaging (MRI).


Patients were selected from the 2200-patient Comprehensive Longitudinal Investigation of Multiple Sclerosis at Brigham and Women’s Hospital (CLIMB) cohort study. Patients were required to have an initial diagnosis of clinically isolated syndrome or relapsing-remitting MS and a minimum of 7 years of prospective follow-up that included yearly brain MRI and biannual clinical visits (n = 219). Patients were analyzed independent of disease-modifying therapy. Patients were classified as having early (recent-onset) MS if they were 5 years or less from their first MS symptom at enrollment or otherwise considered to have established MS (>5 years from onset).


NEDA was defined as a composite that consisted of absence of relapses, no sustained Expanded Disability Status Scale score progression, and no new or enlarging T2 or T1 gadolinium-enhancing lesions on annual MRI. Relapses, progression, and MRI changes were also investigated as individual outcomes.


A total of 99 of 215 patients (46.0%) had NEDA for clinical and MRI measures at 1 year, but only 17 of 216 (7.9%) maintained NEDA status after 7 years. No differences were found in NEDA status between patients with early vs established MS. A dissociation was found between clinical and MRI disease activity. Each year, 30.6% (64 of 209) to 42.9% (93 of 217) of the cohort had evidence of either clinical or MRI disease activity but not both. NEDA at 2 years had a positive predictive value of 78.3% for no progression (Expanded Disability Status Scale score change ≤0.5) at 7 years. Only minor improvement was found in the positive predictive values with additional follow-up of 1 to 3 years.


NEDA is difficult to sustain long term even with treatment. NEDA status at 2 years may be optimal in terms of prognostic value in the longer term. Our results provide a basis for investigating NEDA as an outcome measure and treatment goal and for evaluating the effect of new MS drugs on NEDA.

If you are interested in NEDA you can read this open access paper. 

Do DMT cause NEDA in Relapsing MS, yes they can do and some are better than others. The best appears to be HSCT telling us that relapsing disease is driven by the actions of the immune system

Do the same DMT cause NEDA in progressive MS. I think the current view is that they probably do not do this at least quickly (using lower limb function as an out come)  as evidenced with rituximab, alemtuzumab, caldribine and HSCT, because progressive MS appears to require a different approach to treatment (although some with say Singolimod), not to say that pwProgressive MS will not loose disease activity with such treatments as they do and that has been seen in trials (fingolimod & rituximab etc).

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  • The problem with the CLIMB study it was done largely in an era when we were not treating-2-target. This is why the NEDA rates are so low, i.e. patients were left on DMTs even though their MRIs may have showed new lesions. In the treat-2-target era I suspect NEDA rates will approach 80%. If you are not NEDA you will move onto more effective therapies. Those left on existing treatments will responders, therefore in each-group NEDA rates will improve.

  • The rates are shockingly poor.
    Just moving onto another therapy while you decline is a total lack of respect of MS patients quality of life.
    Get HSCT on the main list ASAP is the answer.

    • Table 2 in the paper contains year-by-year data; one can probably "re-baseline" starting at year 1 instead of year 0. Just by looking, this does not appear to dramatically improve the long-term outcomes

    • Rebaselining once the drug has had time to work, fair enough. But every year is nothing more than manipulating and presenting data to make it look better than it is. Classic example is the Lemtrada extension study, which I have asked about on another post. I am certainly loosing confidence every time you mention 'rebaselining', how do we know this isn't occurring more often than it needs to?

  • Prof. G, to be fair,the authors of the paper did not have tools at their disposal to shut down inflammation effectively. They have been "treating to target" long before the term was popularized, and experimented with reasonable off-target approaches, including a bunch of chemotherapeutics from your "off-label" list. For example, they pioneered cyclophosphamide in MS.

    • Re: "Prof. G, to be fair,the authors of the paper did not have tools at their disposal to shut down inflammation effectively."

      I agree; I simply stressing the point that we need to look to more recent data sets to get an idea of how much more effectively we are managing MS now that we were in the past.

  • Looking at those stats, I realise once more just how honest my medical team have been with me about the efficacy of DMTs to be expected in my case and I am so grateful for that, that I haven't had the added pain of therapies which were never going to work.

  • G: I think that this is a very significant article and warrants a more detailed "discussion" post….

    A panel discussion, videos, etc…. Sustainable long-term NEDA is what we are all after.

  • Perhaps this is an ignorant statement, but the percentages for placebo don't look so bad – at least biotin showed something similar???

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