It is time for NEDA

#MSResearch its NEDA time!!
Is it time to target no evident disease activity (NEDA) in multiple sclerosis? Giovannoni G, Turner B, Gnanapavan S, Offiah C, Schmierer K, Marta M. Mult Scler Relat Disord. 2015;4:329-33

The management of multiple sclerosis is becoming increasingly complex with the emergence of new and more effective disease-modifying therapies (DMT). We propose a new treatment paradigm that individualises treatment based on a choice between two interchangeable therapeutic strategies of maintenance-escalation or induction therapy. We propose treating- to-target of no evident disease activity (NEDA) as defined using clinical and MRI criteria. This algorithm requires active monitoring with a rebaselining MRI, at a point in time after the specific DMT concerned has had sufficient time to work, and at least annual MRI studies to monitor for subclinical relapses. Disease activity on the maintenance-escalation therapy arm of the algorithm indicates a sub-optimal treatment response and should trigger a discussion about switching, or escalating, therapy or the consideration of switching to the induction therapy arm of the algorithm. In comparison, disease activity on an induction therapy arm would be an indication for retreatment or a switch to the maintenance-escalation therapy arm. We envisage the definition of NEDA evolving with time as new technological innovations are adopted into clinical practice, for example the normalisation of whole, or regional, brain atrophy rates and cerebrospinal fluid neurofilament levels.





THIS IS OPEN ACCESS PLEASE FOLLOW THE LINK-CLICK AND DOWNLOAD & READ

IF YOU ARE A NEUROLOGISTS PLEASE DOWNLOAD- CLICK AND READ AND PUT INTO PRACTISE


At present, NEDA is a composite of three related measures of disease activity: (i) no relapses; (ii) no disability progression and (iii) no MRI activity (new or enlarging T2 lesions or Gd-enhancing lesions, Kwhich in our view represent “subclinical relapses”). 
The presence of any of these says your disease is not sufficiently under control. Do something about it,or make sure your neuro does something about this. This is NEDA today.

Dadalti Fragoso Y  says "Although reaching NEDA status has become the goal of many trials and papers, not all researchers like this expression. The concept has still to evolve and the expression “no evidence of disease activity” is controversial. Disease activity in MS goes beyond relapses, disability and MRI images". Why some of us do not like the expression "no evidence of disease activity" (NEDA) in multiple sclerosis. Mult Scler Relat Disord. 2015;4(4):383-4. He says "One major pitfall of the expression NEDA is the fact that there may be evidence that the disease is active in a manner that is not translated into relapses, new lesions on imaging or disability progression" and " Finally, another negative aspect of the expression NEDA is the false sense of security that it may pass to patients, who might interpret the lack of disease activity as cure".


However not to aim for NEDA in the first place is surely a lack of ambition in doing your best for the people in your care and it is arrogant to think that people cannot understand that "no evidence of" means that one can not see this undesirable thing but it is not the cure. 



Yes NEDA focuses on the three evil amigos in NEDA. This is because neuros can do something to achieve this.

However, we can have the four or more evil amigos and so the definition should not be set in stone. NEDA does not mean disease free but it says we are stopping the things that we can measure as being harmful.  

(iv) NEDA-4 is no evidence of brain atrophy. This is a tricky one for some pharma, because their drugs are not good on stopping atrophy and companies lacking agents that affect this aspect are not going to want this in the psyche of neuros.

However, having a shrinking brain is not good, so it should be Bo-Ho and adiós to those drugs and time to escalate to something that does stop atrophy. The other problem with atrophy is that it is not always a standard scan offered...what happens when the scanner is upgraded and their are treatments that cause pseudoatrophy where taking away swelling due to inflammation and makes it look like your  brain is shrinking. Also whilst atrophy does imply nerve loss, this outcome misses a lot of nerve loss. 

So should we have NEDA-5 (v) Maybe no evidence of neurofilament in the cerebropsinal fluid (would you have a lumbar puncture as part of your yearly MOT health check?) or blood or maybe something like NEDA-6 is no cognitive problems. However there is no point measuring lots of things, if they are measuring the same outcome. 

What's in a name it could be called NEDA 2015 this year and NEDA 2018 in 3 years when it will mean something different. Whilst we would like to have "no progression" as part of the equation, at present there is not enough tools to achieve this in progressive MSers although having no disability progression inpart captures this.

However, we think that targeting the three evil amigos as soon as possible will limit the time when progression rears its ugly head and if a cost effective DMT could be found NEDA-3 for the three evil amigos should be a desirable target as these elements are often part of progression. 

As we get better and better treatments we can add more and more desirable outcomes.

CoI: This is a TeamG output. 

Labels: