lol. it's not that i don't appreciate these posts, i do immensely. i feel it's far too early to be calling things a cure, but i agree - if we don't start asking what's a cure and how close are we now, we'll never know what to look for. but that little devil inside me has to ask: how is it fair to call media sensationalist on hsct (and i believe the same could be extended to portrayal of lemtrada in the media) because it mentions the word cure, then do a talk about curing ms and discussing hsct, lemtrada, ocrelzumab and claradbine as the comparative candidates?i do understand the difference: there is a huge difference between calling something a cure and discussing what a cure could look like and referencing it to how close we are with what we've got now. but you can see why it looks confusing to an outsider? ps. thank you for posting the slides. despite the little devil who can't resist making trouble, I do sincerely appreciate the slides. they are super informative on current theories and are far more helpful than the ole tired discussions on relapse rates (relapses do matter a lot, but i want to know more than a drug's relapse rate control). thank you!
I am trying to be provocative and have used NEDA at 15 years as a working definition for a cure. It is clear that none of the patient groups have been followed long enough to make a claim of a cure. However, if we don't define it we won't find it.
Most of the patient populations (at least online) considers cure to be NEDA + Restoration of lost function be it complete or significant.This is why most believe that cure equates to Stem Cell's believing that stem cells result in regenerative measure.The overlap in stem cell reporting that has happened has resulted in this across a broad range of disease and/or disability.Only now is this starting to be addressed as the Stem Cell global research community see's the unstable tall wall that has been built by media. However, its not simply media. There has been a trend in research papers to use terms that make the reporting thereof more colorful lets say.Now they realize the wall built can fall down crushing a whole lot of promising research. The reporting has resulted in stem cell clinics making all forms of claims and thus creating a sized mess across all aspects of stem cells and patient populations.NEDA 15 is an interesting baseline. The immediate question that comes to my mind is onset times of MS being that of young adults (17-25).Since currently the mechanisms resulting in MS are quite unknown though clues lay everywhere is NEDA 15 a good baseline? NEDA 25 would of course be too long a term, aka: Am 25 now and not pronounced cured until 50.Indeed some form of protocol is important to be established towards real world goals. There does however also need be a push towards the realization in patient populations that "Cure" and restorative medicine are two very very different things.Amongst younger folks who perhaps have not incurred sized disability NEDA 15 makes much sense.Towards the older populations (who also tend be the ones as noted in prior correspondence) these are the ones who are highly vocal. Understandably so. Time runs short. But their irresponsibility in said vocalization precedes them doing much harm along the path.
Oh, BTW... Thank you for this!I have posed out the question to many since the aHSCT study in Canada abut this. NEDA has not truly been measured at all across DMT's and some sparks need happen to get clinicians to track and report DMT efficacy now that in terms of time some of these meds are reaching watermarks in time.
4% oonverting to spms after 10 years on lemtrada was reported here. While this is very good. How do you treat those 4%.And then what is going to be the rate after 30 years. Will it be an additional 4% every decade for 12% total after 30 years. Hopefully those 4% are just non-responders but what if time increases the non-responders.
4-5% converting to SPMSS was set against 50% if you did nothing in the same time frame. I spoke to Doctor Coles some time ago and that 4% tended to be the people that started the drug later in their disease course and were people who do worse in terms of responding to the drug.
i understand that the problem with treatment choices for ms is that the numbers are all averages across a population level: there is little predictive information on how each treatment affects an individual's ms. with that context in mind, is there any way that CRAB drugs be a 'cure' according to the current discussion of what a 'cure' could look like for any individual person with ms?
I cannot see how you can speak of a cure until there is a highly effective therapy for progressive MS with little apparent relapse activity / PPMS.
How did this talk go down with your colleagues? Did it generate any discussion and if so what was said?
Until you confirm that highly effective treatments like alemtuzumab and HSCT stop progression to SPMS and halt relapse activity then a cure mention is way to premature.It is possible that highly effective treatments delay the onset of SPMS, isn't the average 50% covert to SPMS 10 years after disease onset and then 90% 25 years? If at 25 years after treatment you have stopped that conversion then a cure can be called. (Reduction could work if highly effective treatment is given early and that shows to be the best responders as your slides imply) i think you could use the term remission much more effectively then cure. 5 or 10 years no activity = remission. 25 years = cure.
There is a school of thought that PPMS is actually SPMS following a benign course of RRMS - what is your opinion of this ?Also from your slides one arm says SPMS is possibly driven by degeneration and another arm says that it is possibly immune driven. Could it be the later for one person and the former for another. I think this could be possible as HSCT seems to halt progression for some and not others.
Agreed. Maybe there is no PPMS. Just SPMS that had an undiagnosed or even clinically silent RRMS phase. Also interested to hear Prof G's thoughts on this?
My understanding is that ms phenotypes are based on clinical presentations. They were invented before neuros knew much about ms/progression (ie. before the wide use of MRIs and other tools – in 1996) and so don't necessarily reflect disease pathology. My understanding (and I could be wrong) is that they cannot tell whether the SPMS and PPMS processes are the same or different, so it's all a guessing game. To make a true distinction between SPMS and PPMS, in my view they need to know the pathology of each and the differences between them: basing it on relapses alone because relapses are so observable is a bit misguided. A mousedoc from this site once called “new lesions” mini relapses, whether they are accompanied by a relapse or not. That made sense to me and my experience with my partner’s MS. Progressive MS, particularly early progressive MS, could be the result of both degeneration and be immune driven.or maybe there is a little bit of progressive MS in most people who are diagnosed with RRMS (I forgot the name of the theory, but Prof G’s theory is that you could have some functions be RRMS and some progressive). My view is that as long as lesions are being created and there are treatments that suppress lesion formation, it matters less what type of MS you have in terms of accessing treatment. My worry with MS phenotypes is how many people are denied treatment who could benefit from it, solely on the basis of the way they present with their MS. Better neuros have been treating people SPMS who show inflammation/new lesions with treatments despite those treatments not necessarily being approved for SPMS – which is great for better neuros and their patients, but not so much for those who are denied it whose neuros haven’t caught on yet. My partner apparently has RRMS. She had over 12 lesions between spine and brain at diagnosis and has had no identifiable relapses, ever. She was initially misdiagnosed with PPMS. She has now had 2 different treatments targeting the immune system. Both helped lessen some of her existing symptoms to different degrees: I’m taking that to be a good sign regardless of the fact that she’s never had an identifiable relapse.
it has been suggested that people are classed as active which helps to say some elements of their condition will respond to them current medications.With the beasties some strains get one attack and go progressive others relapse and remit
with the fluctuations in the severity or frequency of existing symptoms and lack of identifiable relapses: it is theoretically possible that what looks like progressive during one period may actually be more relapsing and remitting over a longer and different period. the first neuro sent my partner home with ppms on diagnosis without offer of any treatment on the basis of our then very naive and insightless understanding of her then symptoms and on the basis of her longest standing symptom (bladder) not improving after iv steriods which were at diagnosis given randomly in timing. first neuro's contact details were given by the ms society.it took 5 months in total to transfer to new neuro (about 2 months to figure out we need another neuro and another 3 months to get what the gp pushed as an 'urgent' appointment). the new neuro offered treatment on presentation on the basis of same mris as the old neuro, at first the suggestion was gilenya, then after reassurance from my partner's oncologist, the offer was from gilenya to tysabri or lemtrada, at my partner's election, with the recommendation being tysabri or lemtrada. by the time of the second appointment with neuro 2, the new mri had shown an enhanced lesion and the recommendation was to hurry. by the time we saw the second neuro, we understood enough about ms to explain that my partner hasn't had recognisable relapses, but that the treatment she received for breast cancer had lots of ups and downs symptom wise - there was always something or other. it's entirely possible she never had an identifiable relapse and it's entirely possible she may have had a relapse which was put down to side effects of her breast cancer treatment. it could have 'relapsed' and 'remitted' without us remembering (there were a lot of things going on) or it could have all hit at once (she was diagnosed with ms 2 years after finishing cancer treatment, which included ovarian suppression or 5 years of induced menopause) or she could have been progressive. at the second appointment in feb last year, my partner's neuro told us she didn't think my partner had ppms like diagnosed with neuro 1, but likely spms or rpms or maybe even rrms. still, she was at that time prepared to give either tysabri or lemtrada - my partner chose tysabri on the basis that she would have hsct in the short future. in june we had a long chat and the neuro confidently revised phenotype to rrms. it was a few months before my partner was to depart for russia so a part of me wondered if it was a 'give you hope' diagnosis - we don't really know but seeing as you're doing this anyway, we may as well give you hope. i asked my partner's neuro (a bit more tactfully than my explanation here) - and she had a longish serious chat about it with us to assure us (me) it was a real diagnosis which was not based on pity lol. It worries me when all this progression and relapsing remitting is based on clinical experience, which seems from my perspective to differ according to whose door you knock on. hopefully my experience with my partner's ms is less rather than more common and hopefully the stories of desperation i read from people with ms are not indicative of everyone's experience today.
I know of several individuals who are doing the HSTC and use of alemtuzumab in Brazil. I find it important study of extended follow-up with individuals with MS, as only will discover the success or failure of a treatment if such monitoring. Now perhaps permanent cure may speak even as treatments for progressive forms of MS are emerging and show the actual effectiveness as well...
Was the talk recorded? I presume not, but if it was, then it would be great to upload it too.
No it wasn't recorded just imagine all those slides in 15minutes
At this point in time reading the papers i can conclude that alemtuzumab and HSCT reduces relapses, atrophy and delays SPMS... now if you ask me this is a cure? As ProfG says it all depends of how we define the C word. For example patients with cancer get treatment, and like in MS some do better than others for unknown reasons, some enter long term remission and some years later it can be claimed that they are "cured", to me 15 years NEDA status seems like an elegant criteria, as its the same used for the so called "bening MS". When we get to this point to claim people with MS are cured, every patient will want to get their chance to get cured and then we will finally say farewell to escalating therapys.
the difference between the cancer analogy and ms is that in cancer, they mostly guesstimate the odds of contracting another cancer. in my partner's case, she was told if she makes it to 5 years without the cancer returning things are looking great, if she makes it to 10 years she is considered in remission. she still has a higher chance of getting another breast cancer than a typical person, but after the 10 year mark any future cancer is considered new, not a recurrence. i'm not sure they have equivalent information for ms. if "it's" (aka activity) is gone for 10 years, what are the chances of it coming back? I'm not sure is any info available to answer it. and so psychologically there is nothing but the waiting game.
Anonhttps://www.surveymonkey.co.uk/r/ZYQGLQL Use of the internet by people living with Multiple Sclerosis to gain information about their medications
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