I finished yesterday emotionally burnt-out; “broken and useless, no longer working or effective” or “kaput” as the Germans would say. I did an all-day clinic with my registrar off sick; it was hard and brutal.
On my way home I wondered to myself if I should change the name of my MS clinic to the ‘Smouldering MS Clinic’. Virtually all of my patients had smouldering MS or as some of you would prefer me to call it PIRA (progression independent of relapses).
With our aggressive campaigns of treat-early-and-effectively, treat-2-target, zero-tolerance, NEDA (no evident disease activity) I think we have exposed the real MS, i.e. smouldering disease. Almost all my follow-up patients were NEDA yesterday and doing ‘well’. However, when I interrogated them almost all of them had subtle symptoms and signs of disease worsening. Worsening fatigue, cognitive slowing, reduced walking distance, dropped feet on exertion, nocturia, sexual dysfunction, numbness and clumsiness of the hand, subtle unsteadiness of gait, poor balance in the dark and when tired, increased leg spasms at night, reduced auditory discrimination, problems with night vision, etc.
The new norm is smouldering MS or more likely the realisation that MS is smouldering MS. Our anti-inflammatory DMTs are doing what we say they should do, i.e. they are stopping focal inflammatory lesions and relapses, but are they getting to the core of the disease, ‘smouldering MS’? I suspect not.
I have argued several times before on this blog that focal inflammation is not MS and that the real disease is what is driving the immune system to produce the focal inflammatory events. I suspect that effective DMTs are simply converting relapsing-forms of MS into what we used to call primary progressive MS.
If you have MS this post will be very depressing, but as soon as the MS community faces up to the above the better. We would then start directing our limited resources to tackle smouldering MS.
I would encourage the funders (government, charitable, private and pharma) to start to divert their R&D spend to addressing smouldering MS. What needs to be done? I would encourage out-of-the-box thinking and support alternative hypotheses of MS. We need deep phenotyping and biomarker studies. More trials on drugs targeting CNS B-cells and plasma cells, microglia inhibitors or activators (both need to be tested), drugs that target astrocyte and oligodendrocyte biology, antiviral trials and trials targeting ageing mechanisms. I would also include systems biology and the impact of diet, etc. on smouldering disease. We need a “Smouldering MS March of Dimes” event to raise the money to get on top of the real MS.
I would like to thank you all for helping out with our grant naming survey. It is clear that from a scientific perspective PIRA (progression independent of relapses) won out. However, smouldering MS came a close second and most commentators prefer this name to describe PIRA to people with MS and their families, i.e. smouldering MS is a lay-term for PIRA. I, therefore, suggest we keep both names in the MS lexicon and use them interchangeably when discussing the real MS.
Don’t be fooled into a false sense of security that because you are NEDA that your MS is under control. We clearly need to go beyond NEDA to tackle MS.