Saturday, 16 July 2016

Defining Progression

Lorscheider J, Buzzard K, Jokubaitis V, Spelman T, Havrdova E, Horakova D, Trojano M, Izquierdo G, Girard M, Duquette P, Prat A, Lugaresi A, Grand'Maison F, Grammond P, Hupperts R, Alroughani R, Sola P, Boz C, Pucci E, Lechner-Scott J, Bergamaschi R, Oreja-Guevara C, Iuliano G, Van Pesch V, Granella F, Ramo-Tello C, Spitaleri D, Petersen T, Slee M, Verheul F, Ampapa R, Amato MP, McCombe P, Vucic S, S├ínchez Menoyo JL, Cristiano E, Barnett MH, Hodgkinson S, Olascoaga J, Saladino ML, Gray O, Shaw C, Moore F, Butzkueven H, Kalincik T; MSBase Study Group. Defining secondary progressive multiple sclerosis. Brain. 2016  pii: aww173. [Epub ahead of print]

A number of studies have been conducted with the onset of secondary progressive multiple sclerosis as an inclusion criterion or an outcome of interest. However, a standardized objective definition of secondary progressive multiple sclerosis has been lacking. The aim of this work was to evaluate the accuracy and feasibility of an objective definition for secondary progressive multiple sclerosis, to enable comparability of future research studies. Using MSBase, a large, prospectively acquired, global cohort study, we analysed the accuracy of 576 data-derived onset definitions for secondary progressive multiple sclerosis and first compared these to a consensus opinion of three neurologists. All definitions were then evaluated against 5-year disease outcomes post-assignment of secondary progressive multiple sclerosis: sustained disability, subsequent sustained progression, positive disability trajectory, and accumulation of severe disability. The five best performing definitions were further investigated for their timeliness and overall disability burden. A total of 17 356 patients were analysed. The best definition included a 3-strata progression magnitude in the absence of a relapse, confirmed after 3 months within the leading Functional System and required an Expanded Disability Status Scale step ≥4 and pyramidal score ≥2. It reached an accuracy of 87% compared to the consensus diagnosis. Seventy-eight per cent of the identified patients showed a positive disability trajectory and 70% reached significant disability after 5 years. The time until half of all patients were diagnosed was 32.6 years (95% confidence interval 32-33.6) after disease onset compared with the physicians' diagnosis at 36 (35-39) years. The identified patients experienced a greater disease burden [median annualized area under the disability-time curve 4.7 (quartiles 3.6, 6.0)] versus non-progressive patients [1.8 (1.2, 1.9)]. This objective definition of secondary progressive multiple sclerosis based on the Expanded Disability Status Scale and information about preceding relapses provides a tool for a reproducible, accurate and timely diagnosis that requires a very short confirmation period. If applied broadly, the definition has the potential to strengthen the design and improve comparability of clinical trials and observational studies in secondary progressive multiple sclerosis.


How do you define progression becomes important when you have a treatment for progression or sadly when you are excluded from treatment because you have progression. This is important when you are being included in trials. You can look at what has happened retrospectively in this study people were assigned to whether they were progressive and 5 years later they reassessed this,  The best definition included a 3-strata progression magnitude in the absence of a relapse, confirmed after 3 months within the leading Functional System and required an Expanded Disability Status Scale step ≥4 and pyramidal score ≥2. It reached an accuracy of 87% compared to the consensus diagnosis. 

Seventy-eight per cent of the identified patients showed a positive disability trajectory and 70% reached significant disability after 5 years which means that they get it wrong 22% of the time. The development of progression occurred about 35 years after diagnosis.

The median is the number given which is the 50% mark when the details are ranked from lowest to highest. The Quartiles given is where the 25% and 75% mark is. 

4 comments:

  1. Is the label 'secondary progressive' really helpful at all as far as PWMS are concerned? I was diagnosed with MS 18 years ago, with very little disability. I now need two sticks to walk quite short distances and a wheelchair for anything longer. So my disease has definitely 'progressed'. But I still have what you might call 'inflammatory activity'. A year ago, I had a bout of trigeminal neuralgia that lasted six weeks. A couple of months ago, I had a lot of problems with my bladder (urgency and frequency) that have now gone away. So do I have RRMS or SPMS? It seems to me it isn't useful to give me either of those labels, it is much better to say that I still have inflammatory activity, so I should be given a drug that helps with that (my choice of drug would be Cladribine, if that's OK).
    I think there are a lot of PWMS who are in my position and that's why I'd say that trying to come up with 'a standardized objective definition of secondary progressive multiple sclerosis' is not helpful. I think you should junk the term 'secondary progressive' and concentrate on whether people still have inflammation. Is there any chance of that?

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    1. Good point and this is why another new definition relates to active MS as this aspect responds to DMT whether you are progressive or not and it is clear that progression becomes evident a few years before relapses cease

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  2. This is the curse of neurologists...all the years of medical education and then limited tools to treat..hence all this effort into diagnosis and classifications.

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  3. lol Adam Bomb: this is a joke about neurologists (armchair neurologist cartoon): https://www.google.com.au/search?q=armchair+neurologist+joke&rlz=1C1CAFA_enAU697AU697&espv=2&biw=1440&bih=799&source=lnms&tbm=isch&sa=X&ved=0ahUKEwjV-JDt_vzNAhVG5WMKHdjZCvYQ_AUIBigB#imgrc=sN6TJJHDZmXVXM%3A

    This is neurologists thinking they've 'overcome' the joke and changed - https://www.google.com.au/search?q=armchair+neurologist+joke&rlz=1C1CAFA_enAU697AU697&espv=2&biw=1440&bih=799&source=lnms&tbm=isch&sa=X&ved=0ahUKEwjV-JDt_vzNAhVG5WMKHdjZCvYQ_AUIBigB#imgrc=sN6TJJHDZmXVXM%3A

    They specifically mention MS as one of the specialities where they've made the difference: thanks to MRIs lol. The self congratulatory article doesn't discuss the limitations of the MRI lol. It's not in keeping with the self back-patting.

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