Isn’t it time we removed the EDSS blinkers? #MSResearch #MSBlog #ResearchSpeak
“The study below demonstrates how poor a predictor relapses are when it come to predicting the onset of the clinically-apparent secondary progressive stage of the disease. Are you surprised? I am not.”
“I personally don’t think relapses are the disease (MS). Relapses are simply a response of the immune system to what is causing MS. This is why in natural history studies, and the placebo-arms of clinical trials, relapses (and focal MRI activity) are such a poor predictors of disability outcomes. Relapses and focal MRI activity are only predictive of disability outcomes when you are on a DMT. Why? I suspect focal inflammatory MS lesions, the pathological substrate for relapses and MRI activity, are the immune system’s response to the the underlying cause of MS and are not MS; i.e. they are not a surrogate of the disease, if they were a surrogate they will be predictive of outcome on and off treatment. This is why MSers who do are doing well on natalizumab develop rebound activity when the drug is washed out; i.e. the immune system finds something in the brain and spinal cord and attacks it. What is interesting is whatever is causing MS does little harm in the absence of an immune response; the one proviso is this statement refers to short and the intermediate term outcomes (< 10 years). We can only answer the long-term question once we seen what happens to MSers who have been on natalizumab for more than 10 years. Anyone prepared to predict?”
“The other mistake the researchers below make is to define SPMS clinically. All the accumulating evidence points towards progressive MS beginning long before it becomes clinically apparent. This is why we need a biological definition of progressive MS that can be applied before MSers become disabled. Only by doing this will be able to prevent, or at least successfully, treat SP and PPMS. There is no point waiting for the horse to bolt. It is about time we, the MS research community, removed our EDSS-blinkers. Hopefully, research funded via the International Progressive MS Alliance will allow this to happen.”
Skoog et al. Continuous prediction of secondary progression in the individual course of multiple sclerosis.Mult Scler Relat Disord. 2014 Sep;3(5):584-92
BACKGROUND: Prediction of the course of multiple sclerosis (MS) was traditionally based on features close to onset.
OBJECTIVE: To evaluate predictors of the individual risk of secondary progression (SP) identified at any time during relapsing-remitting MS.
METHODS: We analysed a database comprising an untreated MS incidence cohort (n=306) with five decades of follow-up. Data regarding predictors of all attacks (n=749) and demographics from patients (n=157) with at least one distinct second attack were included as covariates in a Poisson regression analysis with SP as outcome.
RESULTS: The average hazard function of transition to SPMS was 0.046 events per patient year, showing a maximum at age 33. Three covariates were significant predictors: age, a descriptor of the most recent relapse, and the interaction between the descriptor and time since the relapse. A hazard function termed “prediction score” estimated the risk of SP as number of transition events per patient year (range <0.01 to >0.15).
CONCLUSIONS: The insights gained from this study are that the risk of transition to SP varies over time in individual patients, that the risk of SP is linked to previous relapses, that predictors in the later stages of the course are more effective than the traditional onset predictors, and that the number of potential predictors can be reduced to a few (three in this study) essential items. This advanced simplification facilitates adaption of the “prediction score” to other (more recent, benign or treated) materials, and allows for compact web-based applications (http://msprediction.com).