Thursday, 22 March 2012

Relapses count

Lublin et al. Effect of relapses on development of residual deficit in multiple sclerosis. Neurology. 2003 Dec 9;61(11):1528-32. 

OBJECTIVE: To determine the percentage of MSers with residual deficits following MS exacerbations and the magnitude of those deficits using a database of pooled placebo patients from clinical trials.

METHODS: A database of MSers assigned to the placebo group in several randomized clinical trials was queried to determine those patients with Expanded Disability Status Scale (EDSS) and Scripps Neurologic Rating Scale assessments prior to, at the time of, and after an acute exacerbation of MS. The extent of deficit present at these time points was compared to determine the acute effect of exacerbations and the degree of persistent disability.

RESULTS: Forty-two percent of MSers had residual deficit of at least 0.5 and 28% had residual of > or =1.0 EDSS units, at an average of 64 days after an exacerbation. The results were reproduced across subsequent exacerbations and were sustained over time. The subgroup of MSers with measurable change in EDSS during the exacerbation had more extensive residual impairment on the follow-up visits. Similar results were seen when the Scripps score was examined.

CONCLUSION: MS exacerbations produce a measurable and sustained effect on disability.

"This data from trials suggests that relapses do count for MSers with persistent or residual disability after relapses. Would you want to continue having relapses if you could have them stopped with a DMT? In addition, there is increasing evidence  that DMTs have a long-term impact on disease course, the most striking data is the impact on survival at 21-years."
Other posts of interest:

18 Feb 2012
Conclusions: There was a significant survival advantage in this cohort of patients receiving early IFNB-1b treatment versus placebo. The treatment-related increase in survival was unchanged by the inclusion of baseline ...

29 May 2011
There is one caveat to these data; IFNbeta has many actions in the body and the improvement in survival may be due to other mechanisms independent of MS. For example, IFNbeta may improve survival by preventing ...

17 Feb 2012
"This delay in disability progression on DMTs has also translated into an improved survival rate." "With this and other ... Post of interest: Multiple Sclerosis Research: MS and survival - long-term betaferon ... 29 May 2011; ...

6 comments:

  1. This study is a little dated is it not? I could ask a number of questions about this study, but I'll restrict it to just one.

    Published in 2003, this study predates Tysabri. From the evidence I have seen, Tysabri has had a significant effect on the number of relapses in many MS patients, limiting the number of relapses in those who have seemingly aggressive form of the disease.

    How would you view Tysabri in this context? and supplementary question - and probably more difficult- is it the case that on this drug recovery is "better", i.e. less sustained disability. Asking for an experiential view only.

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  2. Excellent question, I wish I had the answer.

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  3. Re: "Dated study"

    I posted this study to remind people that relapses in themselves are associated with the acquisition of disability. Even if their long-term prognostic significance is uncertain. In other words suppressing relapses is an end in itself.

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  4. Re: "Natalizumab"

    As it is so effective in suppressing relapses it is also very effective in delaying disease progression. In fact a lot or MSers find themselves improving on Natalizumab.

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  5. Hi Prof G,

    The term ‘relapse’ has come up a lot recently as a marker of measuring the severity and progression of RRMS. I understand the pattern of the RRMS graph - it’s what defines the ‘spikes’ I’m unsure of.

    I’d be grateful if we could we go back to basics for a moment:

    How do you identify a ‘relapse’ in comparison to the usual ebb and flow of symptoms? I’m thinking in particular of the large number of RRMS patients with fluctuating symptoms in their ‘remissions’.

    I would imagine that suddenly not being able to walk unaided for several months is a relapse.

    But, for example, is a mild symptom, such as tingly hand for two weeks classed as a relapse?

    Is a symptom (eg. foot drop) returning for a month, after an absence of 6 months classed as a relapse?

    In my experience, symptoms come and go independently and at different times, but there always seems to be something hanging around. I’ve never been sure how this relates to a pattern of ‘relapses and remissions’.

    Also do you have links to these articles you referred to earlier today:

    “…several publications have now shown that MSers on DMTs who continue to relapse and/or acquire new MRI lesions do very badly in terms of future disability progression.”

    Thanks

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  6. Re: "What defines the ‘spikes’?"

    Please read my previous post: http://multiple-sclerosis-research.blogspot.de/2011/07/what-is-relapse.html

    An issue alluded to is pseudo-relapses; these are typically a recrudescence of symptoms from previous relapses that occurs after exercise or heat or occur in association with an infection. These symptoms usually come and go over hours.

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