Sunday, 10 August 2014

Age and PPMS disease course

Are you a PPMS pessimist? There is no need to be. #MSBlog #MSResearch

"The following paper demonstrates that the prognosis of PPMS is poor with age being the most important risk factor predicting outcome. More than 50% of PPMSers need a walking stick within 10 years of disease onset. This is unacceptable and we really need to do something to alter the course PPMSers; no wonder PPMSers feel frustrated and left out. This data will help us design future trials for PPMS. I have previously discussed in detail the issue of therapeutic lag and hope PPMS trialists are taking this into account when designing trials. We simply need to make PPMS trials longer and event driven to make sure we are not missing a treatment effect because our trials are too short. Fortunately, the fingolinod PPMS trial is event driven; so the trial has a good chance of giving us a definitive result. Since noting therapeutic lag I have changed my opinion about the chances of the fingolimod in PPMS trial being positive to over 50%. I know that a lot of my colleagues disagree with me and have heard them stating that the study will be negative. At least nobody can  accuse me of being a PPMS pessimist. I think Novartis will be reporting the headline results of trial in late December or early January. Fingers crossed!"


"The age predicting disease progression is now a common theme across the spectrum of MS and needs a lot of attention. If the main driver of progressive MS is age-related and involves mechanisms that underpin premature ageing we need to join forces with the ageing researchers to work with them. May be what we need in progressive MS are drugs and treatments that target ageing. This is why brain health is becoming so important for MSers."

Epub: Koch MW, Greenfield J, Javizian O, Deighton S, Wall W, Metz LM. The natural history of early versus late disability accumulation in primary progressive MS. J Neurol Neurosurg Psychiatry. 2014 Aug 4.

BACKGROUND: Primary progressive multiple sclerosis (PPMS) is the least common MS disease course and carries the worst prognosis. In relapsing-remitting multiple sclerosis (RRMS) disability accumulation occurs in two distinct phases, but it is unclear whether this is also true for PPMS. Here we investigate factors associated with early and late disability accumulation in PPMS.

METHODS: We investigated the influence of sex, age at disease onset and onset symptoms on time to, and age at, Expanded Disability Status Scale (EDSS) 4 and 6, as well as the time from EDSS 4 to 6 in PPMSers.

RESULTS: We identified 500 PPMSers. The analyses on time to EDSS 4 included 358 PPMSers, and those on time to EDSS 6 included 392 PPMSers. The median times to EDSS 4 and EDSS 6 were 5 and 9 years. The analyses on age at EDSS 4 included 360 PPMSers, and those on age at EDSS 6 included 402 PPMSers. The median ages at EDSS 4 and EDSS 6 were 51 and 55 years. Older age at onset and bilateral motor onset symptoms were independently associated with a shorter time to both EDSS 4 and EDSS 6. Sex and other onset symptoms were not associated with time to, or age at, landmark disability. Only age at onset was significantly associated with the time from EDSS 4 to EDSS 6.

CONCLUSIONS: Age at disease onset is the most important predictor of disability accumulation in PPMS. Bilateral motor onset symptoms were associated with quicker disease progression. In contrast to RRMS, we found no evidence for distinct phases of disability accumulation in PPMS. Disability accumulation in PPMS appears to be affected by the same factors throughout its course.

6 comments:

  1. Hmmm... isnt't this divide between RRMS and PPMS artificial anyway? Isn't it that some people (=men) don't know they have MS until they get to a late stage when disease progresses without clear relapses - then they get diagnosed with PPMS?
    Is there a clear difference in pathology of SPMS and PPMS? ( i.e. would a pathologist blinded to which type of MS the patient had be able to tell which sample is SPMS (with no relapses) and which is PPMS?)

    Just wondered.

    J.

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    1. I would tend to agree with the regard to SPMS and PPMS

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    2. There was also a presentation at AAN suggesting that MS lesions on 7T MRI in SPMS and PPMS are indistinguishable in location, distribution, and presence of a central venule

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  2. Since profound mitochondrial changes occur after demyelination (and also ageing), I think this is the area to focus on for PPMS:

    http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3184498/

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  3. When are results expected to be released in the filingomoid trials?

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