Barts-MS rose-tinted-odometer: ★
I have just been chastised by someone from a Swiss Pharma company for suggesting that siponimod is a cul-de-sac DMT. Why can’t someone who is diagnosed and labelled as having SPMS who is started on siponimod be switched to any other DMT? I agree, but the absurdity of the situation arises because of the rigidity of the Lublin classification of MS (see below) and the salami-slicing of MS into multiple disease entities.
The cul-de-sac is based on the assumption that once you have progressive MS, either primary progressive or secondary progressive MS, you can’t become unprogressive and be subsequently re-diagnosed as having relapsing-remitting MS. This is explicit in the Lublin classification system that defines the clinical course of MS. According to Lublin progressive MS is a one-way street.
The reason we find ourselves in this ridiculous situation is that MS was salami-sliced up into three and four diseases in the 1990s to allow interferon-beta to get licensed under the US Orphan Drug Act. The Orphan Drug Act states that to be an orphan disease there have to be fewer than 200,000 US citizens with the disease. There are clearly more than 200,000 people with MS in the US, but there were less than 200,000 people with relapsing-remitting MS, secondary progressive MS or primary progressive MS in the 1990s. Subsequently, a fourth category was added to the classification system of clinically-isolated syndrome (CIS). Fortunately, CIS is gradually disappearing as the McDonald criteria are gradually nibbling away at this pseudo-category of MS.
Few people are aware of the history of MS becoming four diseases, but the consequences of this to the field have been enormous. For one it means that Pharma has had to do trials in all four ‘pseudo-MS disease states’ at great expense to the field. It has had major psychological effects on people with the disease. When you tell people they have SPMS it is like telling them they have a second disease that until recently was unmodifiable.
The other consequence of MS being three or four diseases is that once you have been diagnosed as having SPMS we are mandated under NHS England guidelines to stop DMTs. This is why most neurologists in the UK avoid labelling their patients as having SPMS.
The Lublin classification system is based on a clinico-radiological worldview of MS and is not underpinned by biology. If you take a biological worldview of MS, which is the correct philosophy based on our current thinking of what constitutes a disease, then MS is one disease and not three or four diseases.
Interestingly, I have been asked by the CONY Virtual Conference organisers to give a keynote plenary lecture on this exact topic, which I recorded yesterday.
The good news is that this Pharma Executive tells me that the Swiss Neurologists have decided that the Lublin classification system is incorrect and that according to the Swiss it will be fine to reverse out of the secondary-progressive cul de sac and to relabel their patients as having relapsing MS and to be able to switch their patients from siponimod to ofatumumab once it is licensed in Switzerland. I sincerely hope the Swiss neurologists publish their new classification system of MS, or MS roadmap, as the Lublin one is out-of-date. More importantly, will the Swiss neurologists be prepared to convince the NHS of their wisdom?
Lublin et al. Defining the clinical course of multiple sclerosis: the 2013 revisions. Neurology 2014 Jul 15;83(3):278-86.
Accurate clinical course descriptions (phenotypes) of multiple sclerosis (MS) are important for communication, prognostication, design and recruitment of clinical trials, and treatment decision-making. Standardized descriptions published in 1996 based on a survey of international MS experts provided purely clinical phenotypes based on data and consensus at that time, but imaging and biological correlates were lacking. Increased understanding of MS and its pathology, coupled with general concern that the original descriptors may not adequately reflect more recently identified clinical aspects of the disease, prompted a re-examination of MS disease phenotypes by the International Advisory Committee on Clinical Trials of MS. While imaging and biological markers that might provide objective criteria for separating clinical phenotypes are lacking, we propose refined descriptors that include consideration of disease activity (based on clinical relapse rate and imaging findings) and disease progression. Strategies for future research to better define phenotypes are also outlined.