Monday, 22 October 2012

Research: PPMS and SPMS are the Same Entity

Orbach R, Zhao Z, Wang YC, O'Neill G, Cadavid D Comparison of Disease Activity in SPMS and PPMS in the Context of Multicenter Clinical Trials. PLoS One. 2012;7(10):e45409. Epub 2012 Oct 1

BACKGROUND: Retrospective single center natural history studies have shown that times to reach disability milestones and ages at which they are reached are similar in primary (PPMS) and secondary (SPMS) progressive multiple sclerosis suggesting that they may be phenotypic variations of the same disease.

OBJECTIVE: Here we compared longitudinal disease activity in SPMS and PPMS in the context of international multicenter clinical trials.

METHODS: We analyzed all objective outcome measures that were systematically collected over 2 years for all subjects randomized to placebo arms in one SPMS and one PPMS clinical trial over the last decade. Conventional and exploratory definitions of clinical disease activity were used. Disease activity was analyzed in 3 different categories intermittent activity, progression, and improvement. Conventional MRI measures and one patient reported outcome measure of quality of life were included when available for comparison. Heat maps were drawn for all results followed by hierarchical clustering.

RESULTS: There were 101 outcome variables from 206 SPMS subjects and 79 outcome variables from 135 PPMS subjects. The comparison revealed that SPMS and PPMS subjects exhibited similar disease activity over 2 years in all but two of the variables in common worsening in the EDSS sensory system was more common in PPMS while worsening on the 9 hole PEG was more common in SPMS. Intermittent activity was the most common pattern of disease activity in SPMS and PPMS. Clinical worsening and improvement occurred at similar frequency in both.

CONCLUSION: Longitudinal disease activity was nearly identical in SPMS and PPMS subjects in the context of the two multicenter international clinical trials we examined.
The conclusions say it all, but we do not think that primary and secondary disease are different but similar variations of a theme


  1. What does this mean for treatment? Surely trials should combine SPMS and PPMS if they are the same.

    Does it tell us anything about the nature of this disease? Primarily neuro-degenerative?

  2. For trials neuros will probably prefer to keep groups similar and seperate as this adds some variability, although the cupid trial involved both SP and PP MSers. Hopefully it says treatment for one treatment for the other.

    "Nature of disease"...maybe.

  3. What does this idea say about those of us who started progressing at a younger age? I think somewhere else progression was related to aging. Are we prematurely old in some way? Or is it something else?

  4. The older you are at diagnosis the increased risk is that you get PPMS

  5. Also seems to be the case that men as a rule generally tend to progress faster than women as a rule, suggesting at least in pre-menopausal women oestrogen is neuroprotective (as seen in stroke studies).
    It also depends on where the lesions are, how many and relapse frequency etc.


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