#NeuroSpeak: reclaiming MS as one disease

Redefining what is a relapse and making MS one disease? #1-disease-not-2-or-3-diseases #NeuroSpeak

I was reminded at a meeting last night why it is important to publish consensus statements. Barts-MS hosted a UK NEDA meeting in 2014. As a group of UK MSologists we reached a consensus that we would stop referring to new MRI activity as 'MRI activity' and start to refer to it as a 'subclinical relapse'. In other words we all agreed to change our working definition of a what constitutes a relapse. This is not new. I was involved in another consensus meeting in 2010, held by the CMSC, during which we came to the same conclusion and published our recommendations in 2013. The problem is we didn't publish our meetings conclusions. I will now harass the chair of the meeting to get typing. 

We also did a survey on this topic in 2014 and you the community who read this blog agreed with us. 



Changing the definition of what constitutes a relapse has implications for how we use DMTs in clinical practice and challenges the older NICE guidance on not being able to escalate DMTs on MRI criteria alone. To escalate from a platform, or a 1st-line, DMT you need to have clinical attacks. However, the newer NICE guidance allows alemtuzumab to be prescribed to pwMS with active MS defined either clinically or on MRI and to retreat on MRI activity . The latest guidelines therefore recognise that clinical attacks and MRI activity mean the same thing biologically; i.e. that MS is active. This position statement is also in keeping with the new 2013 Lublin criteria of classifying MS disease activity. 

One of the consequences of this change is that pwPPMS who have active scans will be reclassified as having relapsing MS. This is not a bad thing because it starts to bring MS back under one umbrella. This also become less relevant with the emergence of effective DMTs for PPMS. Ocrelizumab now has a US label for relapsing forms of MS and PPMS. Is there a population of people with MS that is not covered by this label? Yes, patients with inactive MS defined clinically and on MRI. The latter is disease course agnostic. 

All this supports our campaign that MS #1-disease-not-2-or-3-diseases.

Cook et al. Use of Magnetic Resonance Imaging as Well as Clinical Disease Activity in the Clinical Classification of Multiple Sclerosis and Assessment of Its Course: A Report from an International CMSC Consensus Conference, March 5-7, 2010. Int J MS Care. 2012 Fall;14(3):105-14.

It has recently been suggested that the Lublin-Reingold clinical classification of multiple sclerosis (MS) be modified to include the use of magnetic resonance imaging (MRI). An international consensus conference sponsored by the Consortium of Multiple Sclerosis Centers (CMSC) was held from March 5 to 7, 2010, to review the available evidence on the need for such modification of the Lublin-Reingold criteria and whether the addition of MRI or other biomarkers might lead to a better understanding of MS pathophysiology and disease course over time. The conference participants concluded that evidence of new MRI gadolinium-enhancing (Gd+) T1-weighted lesions and unequivocally new or enlarging T2-weighted lesions (subclinical activity, subclinical relapses) should be added to the clinical classification of MS in distinguishing relapsing inflammatory from progressive forms of the disease. The consensus was that these changes to the classification system would provide more rigorous definitions and categorization of MS course, leading to better insights as to the evolution and treatment of MS.

Lublin et al. Defining the clinical course of multiple sclerosis: the 2013 revisions. Neurology. 2014 Jul 15;83(3):278-86.

Accurate clinical course descriptions (phenotypes) of multiple sclerosis (MS) are important for communication, prognostication, design and recruitment of clinical trials, and treatment decision-making. Standardized descriptions published in 1996 based on a survey of international MS experts provided purely clinical phenotypes based on data and consensus at that time, but imaging and biological correlates were lacking. Increased understanding of MS and its pathology, coupled with general concern that the original descriptors may not adequately reflect more recently identified clinical aspects of the disease, prompted a re-examination of MS disease phenotypes by the International Advisory Committee on Clinical Trials of MS. While imaging and biological markers that might provide objective criteria for separating clinical phenotypes are lacking, we propose refined descriptors that include consideration of disease activity (based on clinical relapse rate and imaging findings) and disease progression. Strategies for future research to better define phenotypes are also outlined.

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