Disability improvement
Is multiple sclerosis a progressive, irreversible, unidirectional disease?
Is multiple sclerosis a progressive, irreversible, unidirectional disease?
A recent subscriber said that people with MS should expect their MS to get relentlessly worse and that it is unidirectional. Dare I disagree?
After participating in the alemtuzumab CARE-MS trials, I saw many pwMS who were disabled who received alemtuzumab notice disability improvement or stabilisation, with many going into long-term remission. Some of these trial subjects are now living free of disability with no evident disease activity, more than 15 years since they were treated with alemtuzumab. Are they cured of having MS? I think so, which is why I added a line, albeit under construction, to my London Tube map of MS with stops labelled 'long-term remission,' 'MS cure, ' and 'normal ageing. '
The same observations have been reported with AHSCT, and disability improvement is noted with other high-efficacy DMTS when used early, albeit at a much lower rate.
Sadly, MS treatments don’t impact normal ageing, so when pwMS get into their late 50s and 60s, they often notice worsening disability, which is not always due to MS disease activity, but rather superimposed ageing on a damaged nervous system. What protects you from ageing is brain or neuronal reserve, and if MS reduces your reserve, you will notice the effects of ageing earlier. So, not all worsening is MS; it can be ageing and/or another disease superimposed on MS.
I have in the past been heavily criticised for using the C-word. If MS is an organ-specific autoimmune disease with defined mechanisms or if it is due to a virus, e.g EBV, then it should be curable. Don’t you agree? If we don’t define what an MS cure looks like, we will never find it. Maybe you disagree?
Please see ‘To cure or not to cure MS, that is the question (24-Aug-2023)’.
How many of you noticed disability improvement when you started DMTs? Do you agree or disagree with my position on this issue? Is it time to re-examine what a cure for MS looks like? If we don’t, HCPs and pwMS will continue to shun the high-risk treatments such as alemtuzumab, AHSCT and CD19-targeted CAR T-cells.
Objective: To characterize effects of alemtuzumab treatment on measures of disability improvement in patients with relapsing-remitting multiple sclerosis (RRMS) with inadequate response (≥1 relapse) to prior therapy.
Methods: Comparison of Alemtuzumab and Rebif Efficacy in Multiple Sclerosis (CARE-MS) II, a 2-year randomized, rater-blinded, active-controlled, head-to-head, phase 3 trial, compared efficacy and safety of alemtuzumab 12 mg with subcutaneous interferon-β-1a (SC IFN-β-1a) 44 μg in patients with RRMS. Prespecified and post hoc disability outcomes based on Expanded Disability Status Scale (EDSS), Multiple Sclerosis Functional Composite (MSFC), and Sloan low-contrast letter acuity (SLCLA) are reported, focusing on improvement of preexisting disability in addition to slowing of disability accumulation.
Results: Alemtuzumab-treated patients were more likely than SC IFN-β-1a-treated patients to show improvement in EDSS scores (p < 0.0001) on all 7 functional systems. Significantly more alemtuzumab patients demonstrated 6-month confirmed disability improvement. The likelihood of improved vs stable/worsening MSFC scores was greater with alemtuzumab than SC IFN-β-1a (p = 0.0300); improvement in MSFC scores with alemtuzumab was primarily driven by the upper limb coordination and dexterity domain. Alemtuzumab-treated patients had more favorable changes from baseline in SLCLA (2.5% contrast) scores (p = 0.0014) and MSFC + SLCLA composite scores (p = 0.0097) than SC IFN-β-1a-treated patients.
Conclusions: In patients with RRMS and inadequate response to prior disease-modifying therapies, alemtuzumab provides greater benefits than SC IFN-β-1a across several disability outcomes, reflecting improvement of preexisting disabilities.
Classification of evidence: This study provides Class I evidence (based on rater blinding and a balance in baseline characteristics between arms) that alemtuzumab modifies disability measures favorably compared with SC IFN-β-1a.
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Please note that the opinions expressed here are those of Professor Giovannoni and do not necessarily reflect the positions of Queen Mary University of London or Barts Health NHS Trust. The advice is intended as general and should not be interpreted as personal clinical advice. If you have problems, please tell your healthcare professional, who will be able to help you.
so many of your pieces (and the drug trials) seem to be aimed at people relatively recently diagnosed .
but with only(sorry!) 7000 people diagnosed every year, and over 150,000 people in uk living with MS, then surely there are hundreds of thousands of people decades into MS - from before there were DMTs.
where are the trials - or even just some basic thinking - on this big patient group?
pharma wont be interested - most of us will have other long term conditions, simply because we're older.
and we wont be a coherent group - the biggest clue in multiple sclerosis is surely the word 'multiple' (its not just the lesions)
but i think its not only me feels discussions with neurologists are more like a battle / begging for whatever-drug-we-might-possibly-qualify-for rather than a coherent approach to minimise progression and maybe even reverse disability.
relying on mris doesnt help at all: my most recent mri says im stable, but my body doesnt quite agree.
I think its hard to take disability improvement seriously when most of these trials if not all are conducted in RRMS cohorts. To me RRMS is early stage ms or ms that is being kept at bay by the bodies own repair / replenishing processes. As time goes by or people age, ms grows in power like anger in the Hulk, were ms overpowers everything the body tries to do to repair itself. For me, real disability improvement can be measured in spms or ppms cohorts alone and only with combination therapies (i.e immuno therapies PLUS remyelinating therapies ) . The drugs need to slow the immune system attacks as well as repair the damage in these moments of cease fire. Ms is like an evolution of wars… first starts with petty theft, then grows to serious crime, then spreads into militia before going nuclear. Peace for ms is far from reach. A relentless war of zero sum.