I was a meeting this weekend and presented a talk in which I discussed MS being a length-dependent axonopathy. I made the case why progressive MS is modifiable and presented the positive results of the oral low dose methotrexate and ASCEND (natalizumab) trials and said that we had thrown the baby out with the bathwater. If we had interpreted the results of the oral low-dose methotrexate progressive trial from over 20 years ago correctly we would have had licensed therapies for progressive MS decades ago.
I was then told by one of the participants at the meeting that the parcelling 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 to access the market with one pivotal trial, gave them market exclusivity and allowed them to charge much more for their drugs. 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 worse. The latter is interpreted by most people that their disease is not modifiable and that they are not eligible for DMTs. This is incorrect; remember #ThinkHand. In England we are meant to stop DMTs in the SPMS phase. There are also many other reasons to avoid the 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 and terminal. Just as people fear their tumour mutating, and becoming ‘terminal’, people with relapsing MS live in fear of developing progressive MS.
Our PROXIMUS trial, which is now over a year behind in recruitment, 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 have referred patients for this trial simply because it means 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. I recently wrote a short commentary for MSARDs arguing the MS begins long before the first clinical attack, I plan to write a piece on the observations that 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 has done the field of MS a major disservice.