Understarters Orders...whats the plan to ensure the race ends in a good outcome

This weekend's post about alemtuzumab not working in some people after fingolimod begs the question "How we should transition people from fingolimod onto something else?"

We have had this debate about natalizumab already. Look for the posts on this aspect.


These drugs are not killing drugs... they are trapping drugs and for fingolimod they trap disease-causing cells in lymphoid tissue and for natalizumab they trap-disease causing cells in the blood. 

They do not stop the disease process and so the disease causing cells can accumulate and are trapped, whilst drug treatment is in place.

However, see these cells as racehorses waiting to run into your brain, and they are "under starters orders" waiting to go. The gates open and "they're off"

Remove drugs and the cells escape, get into the brain and disease activity occurs.

Whilst some people view progressive MS, as a different disease, this I think is a dumb view and importantly a dangerous view. It is very clear than there are many people with active lesions that come and go as the progressive course carries on. If you look in the pathology of people with progressive MS there are active lesions.

It is clear that some people with progressive MS benefit from immune-inhibition.

However, I think it is also the case that the "racehorse drugs" allow the accumulation of damaging cells in people with progressive MS to such an extent that the drugs convert their subclinical relapsing pathology into relapsing-active MS, with a time-bomb ticking once drugs are stopped.

This is because the horses are all lined up and waiting to go.

Stop drugs and relapse occurs...this is sometimes called Rebound. 
Call it "resumed (synchronized) relapse" in case you don't like the word rebound...but they are damaging by what ever name you call them and it need to be avoided.

Does this happen? Sure it does! DrK a case report please

DrK says "Here you are MD: Davion JB, et al. Two cases of relapses in primary progressive multiple sclerosis after fingolimod withdrawal. J Neurol 2016;263: 1361–3.

However, how do you treat somebody with PPMS and rebound with no licensed options available?  We will hopefully see soon..."

Thanks DrK!

We are in the race for the "Mod me toos" and "Mods in progressive MS" and there are loads and loads of trials in relapsing MS and we will see them in progressive MS too if siponimod gets a green light. 

If deemed a success companies may contiune to supply drug as this gives them important safety data, but if the study is deems to have failed drug supply may be stopped, or if it is a small company a failure means they are gone and drug supply will be stopped

If it clear to me, that you need to ask "Once the trial ( I am volunteering for) finishes, what are the plans after the trial if it is a success or a failure? What happens when the drug stops and what is in place to limit rebound?

Rebounds won't have happen in everybody but if they do, people can not afford to loose more brain, because we haven't thought of a solution and got a plan in place. This goes out to pharma and the neuros.