Sunday, 21 December 2014

ClinicSpeak: predicting progression in MS

How predicting prognosis affects DMT decision making. #ClinicSpeak #MSBlog #MSResearch

"This study below is kind of what I do in clinical practice using a different technique. When looking at patients with early MS I put them into three categories; those with a active MS and a poor prognostic profile, those with active MS and an intermediate prognostic profile and those with inactive MS and a favourable prognostic profile. The latter patients are not eligible for DMTs under NHS England guidelines and are monitored to see if there disease become active, i.e. if they move into one of the other active categories. We tend to define activity as being clinical (relapses) or MRI (subclinical) activity in the last 12 months. Those patients in the active and poor prognostic category tend to have highly-active MS or rapidly-evolving severe MS and as a result tend to be offered access to highly-effective DMTs first-line; the latter is always in accordance with our NHS England prescribing guidelines. Those patients in the intermediate group are the most challenging and take the most time in clinic with regard to counselling. When you have a choice it always takes more time. We know if we leave you to face the natural history of MS the majority of you would end-up disabled; all it takes is sufficient time for this occur. We therefore offer you a choice of DMTs and more recently we have been able to include alemtuzumab for this groups of patients; please note alemtuzumab has a very liberal 1st-line license in the UK and Europe and therefore patients need to be told about its potential risks and benefits. Some neurologists disagree with this approach, but may change their practice once they get comfortable using alemtuzumab 1st-line. At the top of the decision making tree is the choice between an induction therapy and a maintenance-escalation approach; the philosophy of these two treatment approaches is so different that this decision should be made first. The whole aim of our treatment approach is to try and shift as many patients into the inactive, favourable prognostic groups using DMTs. Only be doing this will we reduce the overall burden of MS; the latter is what drives our treat-2-target approach of NEDA with zero-tolerance."

Scott et al. Relapsing multiple sclerosis patients treated with disease modifying therapy exhibit highly variable disease progression: A predictive model. Clin Neurol Neurosurg. 2014 Dec;127C:86-92.

OBJECTIVE: To describe a "new natural history" of multiple sclerosis (MS), characterizing three patterns of progression in Relapsing MS (RMS) patients during the "treatment era," using newly developed definitions. By utilizing our simple model we intend to predict which patients are most likely to reach an EDSS of 6.0.

METHODS: We stratified MS progression into three distinct patterns: aggressive MS (AMS), intermediate MS (IMS) and mild MS (MMS), based on Expanded Disability Status Scale (EDSS) score rate of change. These groups were compared for progression of EDSS before and after reaching these definitions.

RESULTS: The three groups remained significantly different in terms of disability throughout their disease courses p≤0.001; 98% of the patients used disease modifying treatments (DMTs). AMS patients represent a significantly more disabling and aggressive form of MS than the IMS group.

CONCLUSIONS: Transition from relatively mild MS to aggressive course may begin at any time in the first 15 years, despite DMTs. Our definition for AMS is unique and identifies a group of patients who become permanently disabled within two years after a variable amount of time in a benign phase, despite treatment with modern DMTs.

CoI: multiple


  1. Are there also patients with inactive MS and a poor prognosis?

  2. What is the definition of high versus low lesion low on MRI ?

    1. Excellent question! Would love to see an answer posted........... and/or maybe an item in the blog glossary

  3. In the conclusion the authors state:"Transition from relatively mild MS to aggressive course may begin at any time in the first 15 years, despite DMTs." Isn't this the purpose of the DMTs, to control inflammation and to prevent transition to aggressive disease? If patients are still progressing despite treatment is this a failure by clinicians to initiate a timely switch to an induction therapy? Or maybe it would be more effective to treat patients with an induction therapy from the onset rather than continuously use less effective DMTs and that way save money and better prevent disability in the long term.

    1. This data is from the age of the original DMT which were not that effective in creating NEDA, I suspect the story will be different in the future with more eefective treatments


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