Tuesday, 9 October 2018

ECTRIMS 2018: will MS become one again?

I arrived in Berlin yesterday and already I am seeing ECTRIMS 2018 turning into a battle between the lumpers and splitters, i.e. is MS one, two or three diseases. 


Making Berlin one again

Roche, who has ocrelizumab licensed for relapsing and primary progressive MS want MS to be one disease. On the other hand, Novartis who have just submitted siponimod to the FDA for SPMS want it to be at least two diseases. This new battle helps nobody. We have been running the #MS-is-1-not-2-or-3-diseases for several years on this blog and I am not going to change my position on this.

Our MS as a length-dependent axonopathy hypothesis makes a strong case of MS being one disease, which is why we are arguing that advanced MS (formerly known as progressive MS) is modifiable. This principle underpins our #Chariot-MS and the #Oratorio-Hand studies and explains the positive low-dose oral methotrexate and ASCEND (natalizumab) trials. If we had interpreted the results of the low-dose oral methotrexate progressive trial from over 20 years ago correctly we would have had licensed therapies for progressive MS decades ago; yes, decades ago.

In reality, the salami slicing-up of MS into relapsing and non-relapsing forms, and of chronic progressive MS into primary and secondary progressive MS, was driven by money. When the interferon trials started it was important to make MS an orphan disease, i.e. to having fewer than 200,000 patients classified as having the disease. Being an orphan disease allowed Pharma (Bayer-Schering) to access the market with one pivotal trial, gave them market exclusivity and allowed them to charge much more for their product. The consequences of this is that we have divided MS into being many diseases, which is to the detriment of people with MS. The consequences of this are not trivial. Being diagnosed as having MS is bad enough, but then being diagnosed as having secondary-progressive disease is like getting another disease. The latter is still interpreted by most people with MS as now having a disease that is not modifiable. For example, in the NHS we are meant to stop DMTs in patients who develop SPMS. There are also many other reasons to avoid a diagnosis of SPMS.

An analogy to the RRMS vs. SPMS dichotomy is being diagnosed with a low-grade tumour, that on average is quite indolent and slow growing, however, after time the tumour mutates to become highly-malignant, life-threatening and often terminal. Just as people fear their tumour mutating, and becoming 'terminal', people with relapsing MS live in fear of developing progressive MS.

Recruitment for our PROXIMUS trial, which is now closed and being analysed, has been a victim of MS being two and not one disease. We made the mistake of calling it a secondary progressive trial. Very few of my colleagues referred patients for this trial simply because it meant diagnosing their patients as having early SPMS. Almost every neurologist I know avoids making a diagnosis of SPMS as long as possible because of the repercussions it has for their patients.

I think we need to turn the clock back and get rid of arbitrary, non-science, based definitions of MS. They don't help us clinically. MS begins long before the first clinical attack. Similarly, progressive MS is present from the start of the disease. There is simply no magic point in time when you become SPMS. Dividing MS into relapsing and progressive phases may have helped Pharma get interferons licensed under the orphan-drug act, made them lots of money, but it is now doing the field of MS a major disservice. 

Now that there are marketing reasons to keep MS sliced-up as multiple diseases I can only imagine the Pharma shenanigans that will emerge. ECTRIMS-BERLIN 2018 is witnessing the first shots of this epic battle. Who will win? At least this new battle buries the dogma that advanced, or progressive, MS is not modifiable. We have won one battle only to replace it with another one. 

I am determined to remain an optimist and view this change in perspective as being positive for the field; at least both sides believe progressive MS is now modifiable.  

CoI: multiple 

4 comments:

  1. " MS begins long before the first clinical attack"

    Really?

    So how to explain this?

    MRI evidence suggests that late onset MS is due to true late onset rather than late presentation

    https://onlinelibrary.ectrims-congress.eu/ectrims/2018/ectrims-2018/228525/sarah.quraishi.mri.evidence.suggests.that.late.onset.ms.is.due.to.true.late.html?f=media=3*search=S.%20Quraishi*listing=3*browseby=8


    Obrigado

    ReplyDelete
    Replies
    1. "MRI evidence suggests that late onset MS is due to true late onset rather than late presentation"

      Suggests PPMS is not just MS w/o relapses in later progressive stage.

      Delete
  2. Does it make any difference if MS in 1 or 2 or 3 diseases, as long as all get treated? RRMS with many DMTs, PPMS with ocrevus and SPMS with siponimod?

    ReplyDelete
  3. Nice post; more of this please. This kind of post is what made this blog what it is.

    ReplyDelete

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