Relapses vs. MRI-activty vs. progression vs. brain atrophy

"Some of you who have been following this blog and my recent posts will realise that I have had a change of mind. I have been sceptical about the publications showing a very poor correlation between relapses (frequency and severity) and disease progression. Apart from relapses in the first two years, after the first attack, there is no correlation between subsequent relapses and long-term outcome. Therefore reducing relapses or rendering MSers relapse-free, after the first two years, may not prevent or delay the onset of SPMS and may therefore not impact on long-term prognosis. In fact, we don't have the necessary long-term data that suppressing the relapses in the first two years is effective either. However, the short to intermediate-term data looks very promising; i.e. the earlier, and more actively, you treat MS the better the outcome." 

"Data from several emerging DMTs now supports the natural history studies and the observation that there is a disconnect between relapses and disease progression and importantly an impact on brain atrophy. We have evidence that brain atrophy is a good surrogate of disability progression. Brain atrophy is the biomarker that best captures loss of neurones and axons and is probably the most important MRI biomarker of disability progression to have emerged; in particular atrophy of the grey matter."

"What would you want from your DMT; being relapse-free, without the DMT necessarily having an impact on long-term disability, or brain atrophy? Would you prefer a DMT to delay the rate of brain atrophy, with the promise of this will translate into long-term disease progression? Many of you will say this is a no-brainer; i.e. I want to be relapse-free, disease-progression free, MRI disease activity-free and with a reduction in the rate of brain atrophy to a rate that is expected for age. I agree that it may be a no-brainer, but is it achievable? The current crop of DMTs don't offer this treatment target, or we don't have the data yet, to show that we can achieve this in the long-term."

"May be you should be asking your neurologist what is the evidence that the DMT they are recommending prevents or delays the acquisition of long-term disability and what does the DMT do in relation to brain atrophy? I would be interested in knowing their answers."

"I am at a meeting in Barcelona and I am about to give my "Treatment Highlights ECTRIMS" talk for a second time and will focus on getting this point across! I will update you on the feedback."

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