Are MS drugs a waste of time......for progressive MS

Lorscheider J, Jokubaitis VG, Spelman T, Izquierdo G, Lugaresi A, Havrdova E, Horakova D, Trojano M, Duquette P, Girard M, Prat A, Grand'Maison F, Grammond P, Pucci E, Boz C, Sola P, Ferraro D, Spitaleri D, Lechner-Scott J, Terzi M, Van Pesch V, Iuliano G, Bergamaschi R, Ramo-Tello C, Granella F, Oreja-Guevara C, Butzkueven H, Kalincik T; MSBase Study Group. Anti-inflammatory disease-modifying treatment and short-term disability progression in SPMS. Neurology. 2017 Aug 9. pii: 10.1212/WNL.0000000000004330. doi: 10.1212/WNL.0000000000004330. [Epub ahead of print]

OBJECTIVE: To investigate the effect of disease-modifying treatment on short-term disability outcomes in secondary progressive multiple sclerosis (SPMS).
METHODS: Using MSBase, an international cohort study, we previously validated a highly accurate definition of SPMS. Here, we identified patients in MSBase who were either untreated or treated with a disease-modifying drug when meeting this definition. Propensity score matching was used to select subpopulations with comparable baseline characteristics. Disability outcomes were compared in paired, pairwise-censored analyses adjusted for treatment persistence, visit density, and relapse rates.
RESULTS: Of the 2,381 included patients, 1,378 patients were matchable (treated n = 689, untreated n = 689). Median pairwise-censored follow-up was 2.1 years (quartiles 1.2-3.8 years). No difference in the risk of 6-month sustained disability progression was observed between the groups (hazard ratio [HR] 0.9, 95% confidence interval [CI] 0.7-1.1, p = 0.27). We also did not find differences in any of the secondary endpoints: risk of reaching Expanded Disability Status Scale (EDSS) score ≥7 (HR 0.6, 95% CI 0.4-1.1, p = 0.10), sustained disability reduction (HR 1.0, 95% CI 0.8-1.3, p = 0.79), or change in disability burden (area under the EDSS-time curve, β = -0.05, p = 0.09). Secondary and sensitivity analyses confirmed the results.
CONCLUSIONS: Our pooled analysis of the currently available disease-modifying agents used after conversion to SPMS suggests that, on average, these therapies have no substantial effect on relapse-unrelated disability outcomes measured by the EDSS up to 4 years.

I'm back....(What! you didn't notice that I've not been around and that there were slow responses).

I been in the Third World.....................of internet access, with zero email and essentially no access to the web...with even the paid-for "high speed" (yeah right) net.


Where?..........yep you got it........in the USA. 

In a number of National Parks the internet access has been woeful

Who would have thought that a gas (petrol) station in the middle of nowhere, would turn out to be a cyber oasis compared to the dearth for International Travellers.


However, I saw an amazing example of "thinkhand" and why giving access to people in wheelchairs access to treatment to save upper limb function is something we really must do. 


If you look at the picture above you can see on the right of the top of the waterfall there is a platform, which is full of people watching the waterfall. This waterfall is 308 feet (94 metres), where the top is some 600 feet down the canyon.  


I was passed on the way up the canyon, by a hand-driven wheelchair, OK with some help from their partner and encouragement by the kids. They were at the top looking down by the time I got there. Why shouldn't we stop deterioration of loss of hand function.


Anyway more news from the MSBase people and they haven't done a post on this one but it is something the Pharmaceutical nihilists will be shouting out loud about why it is OK to do nothing. This study suggests that use of DMT does not influence the course of secondary progressive MS if used after onset.


ProfG will be sitting on a beach somewhere in the USA pondering what this means for his therapeutic lag idea, but more importantly what it could mean if hand function was the main outcome. 


The take home message of this story is more reason not to use DMT in SPMS. Which is not what we have been saying.

There were about 25% in the untreated ground that had MRI lesions and about 20% in the treated group (so not effectively treated)

However, you can see the (median) follow up was for only two years although it was longer for many people, and when the ASCEND trial of natalizumab looked  and there was no change in EDSS over two years. However if the trial was followed for 3 years then they was an influence. So the follow up in this study may not have been long-enough for the therapeutic lag effect to show itself, (if it existed, which it didn't when it was looked for).

Likewise, I really would like to see if you look at the effect of only highly-effective DMT/HSCT use and subsequent course of MS. Yes, I know that use of CRAB drugs is the real life situation, but the picture is going to be muddied if you include use of CRAB drugs. 

We know progression will often occur because this has already been seen with alemtuzumab and HSCT, but will the rate of decline change? 

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