“My post below from yesterday has generated a lot of discussion. The immunological observation that alemtuzumab leaves the rebooted immune system in a mess and HSCT doesn’t is not a trivial one. It means that in terms of long-term safety HSCT may in fact be safer than alemtuzumab despite a higher early risk associated with the procedure. The only way we are going to sort this out is by doing a head-2-head study. In addition the study should be large enough and done well enough to get HSCT licensed as a treatment for MS. Without a license the payers won’t pay for the procedure and neurologists would be forced to continue prescribing licensed therapies. It is clear that as a community you want the option of having a HSCT. If that is the case you need to start a lobby, or petition, to get the MS Society, NHS, NIHR, MRC, Wellcome Trust, etc. to take notice and fund a trial. If you want us to help lead the lobby we would be willing to do so. My resistance to HSCT as a legitimate treatment for MS is gradually dissipating a as I read and understand more about the procedure and its immunological effects.”
“I had a very interesting discussion this week with immunologists and MSologists about induction therapies. My definition of an induction therapy is any therapy that is given intermittently as a short course and works by depleting a subset, or subsets, of cell(s) and results in long-term remission of MS disease activity. In comparison to maintenance therapies, retreatment with an induction therapy is only necessary if MS disease activity reemerges. Current examples of induction therapies are alemtuzumab, cladribine, HSCT (hematopoietic stem cell therapy) or bone marrow transplantation (BMT) and possibly the anti-CD20s (rituximab, ocrelizumab and ofatumumab).”
“The most interesting aspect of our discussion was the discussion about what happens to the immune system when it reconstitutes itself. I haven’t quite appreciated that with HSCT, or BMT , may be a better rebooter in that it results in a much healthier immune system post-induction; i.e. the reconstituted immune system post-HSCT may be closer to normal than the immune system post-alemtuzumab and the other therapies. This insight is in fact blindingly obvious; MSers are at very high risk of developing secondary autoimmunity post-alemtuzumab compared to post-HSCT. If HSCT became widely available as a treatment for MS this observation may make it more appealing than alemtuzumab. The other factor is efficacy; based on the open-label studies of HSCT, the reported NEDA rates seem to be higher than those achieved with alemtuzumab treatment, which implies that HSCT is likely to be more effective than alemtuzumab. I was also surprised to find out that in the UK HSCT will probably turn out to be cheaper than treating someone with alemtuzumab. All these factors (healthier post-induction immune system, greater efficacy and more cost-effective, make it essential that we do a trial comparing alemtuzumab to HSCT. May be we should take the ZEUS trial forward. What do you think?”
You are asking MS'ers if the most effective treatment out there should have more trials so that it can become mainstream? I don't understand why you would need to ask that. It's like asking 15 years ago should we persist with alemtuzumab Vs interferon. It makes me questions motives of neurologists when many say they are looking for the best treatment out there for their patients but they ignore the data published and then hide behind the fact that it's not licences by NICE.You are the experts, you can change opinion by proposing changes with scientific back up to NICE. Stop hiding behind them and try and make a difference for your patients who say by day are losing a piece of their life to this disease.
Who are the people who are going to change opinion? If it were only that simple. This is exemplified by the re purposing issue, there is placebo controlled data and still no one has a clue how this can be done and here you are asking to compete against licensed products, is a different kettle of fish. Having been banging a against a brick wall for a few years it is not simple
I think you need to explain more what HSCT is. As I understand it the term refers to stem cell replacement, but it is actually removing your own stem cells from your blood, chemotherapy and then replacing your stem cells with your own. Is that correct? (I know there is more to it)
Please have a look at the diagram onhttp://multiple-sclerosis-research.blogspot.com/2015/05/hsct-hamburg-experience.htmlThe idea is to mobilise your own stem cells from the bone marrow and you harvest these stem cells of blood cells called CD34+ and then store them and then destroy the current immune system with drugs and then you transplant the CD34+ stem cells and they then grow to produce new white blood cells giving you an immune repertoire hopefully without MS. Whilst your immune cells are repopulating you are at real risk from infection and I heard the risk of death was about 0.5% which is a 10% drop from what it used to be. Because of the mortality risk, it has been seen as a third line treatment
These academic discussions are all very interesting, but never address the issue which is most relevant to people with MS. People with MS don't want to become disabled / continue to accrue disability. With disability comes the loses (sport, relationships, work, quality of life). I can't understand why the researchers / neuros can't understand this most basic concept. We need treatments which maximise the chance of us not becoming disabled. As a neuro you should be vigorously encouraging your patients to take those treatments which maximise their chances of living a normal life. I know two women who have had MS for c15 years. One is bed bound and on her last legs. The other is about as disabled as you can imagine – her teenage children have done terribly at school as a result and her husband can't work because of the stress. These are the real risks of not taking any treatment / taking low efficacy treatments. Of course the neuros don't see this final stage – the poor old MS nurse gets the crappy end of the stick. If only the so-called specialists would start treating MS like cancer as MS can be as devastating and needs to be whacked down as early as possible rather than allowed to fester on.
Theoretically anyone with active MS can be prescribed alemtuzumab, which is the major sledgehammer available, yet few MSers seem to wanting this and neuros don't seem to want to prescribe this so I suspect it is a two way street.However, is suspect access treatments is going to get tougher as austerity takes hold.
I think this is sad. Please don't throw out the baby with the bath water. Yes, alemtuzumab is not perfect and we should be looking for better alternatives, but its the best we have available at the moment. As you've said on countless occasions, time is brain, and waiting a few years for a nonmyeloablative HSCT to possibly become accepted practice whilst putting today's MSers off alemtuzumab because of its side effects makes a difficult decision more difficult if we feel you don't believe in it.
Not sure where the idea comes from about lack of belief in activity. Not from me
Wasn't lack of belief in activity, it was Prof G's yesterday's post- HSCT gives better immune system, possibly more effective, cheaper. Just concerned it would put MSers off going for alemtuzumab if they think something better is around the corner
If HSCT could achieve the same benefit but without the undoubted negative side-effects of alemtuzumab, then I'm sure we'd be all for it. How much would it cost the NHS though?
HSCT, which would possibly be a cheaper option than alemtuzumab, is not round the corner and is some way from it. The MIST trial is some way off finishing away and as you know it takes time before regulators give thumbs up.The grass will always be greener in the future but people have to make choices now, with what is available now. If you wait for something that may never happen, that is your choice as it is you that has to live with the consequence of your choice.
Your poll results, you hardly gave people enough time to vote and only published the results once. I think you need to explain in more detail the trials and the current results, and.give people more time to vote. You were very vague about HSCT and I don't believe have ever stated until the above article that current published literature shows HSCT to be more efficient than alemtuzumab. You ask MS'ers here is the most effective treatment we have, do you want it? I think they will say yes. But patients like to have treatments endorsed by their doctors as you are the experts.
Not enough time to vote…..so about a few minutes was not enough time:-)
Finally it seems that Team G is recognising that alemtuzmab is going to cause greater health issues in the long term and may catastrophically fail as an MS treatment.This post reads like someone trying to cover their backside.
Oh rubbish.If it fails as a treatment that is the fault of MSers and Neuros and the regulators, and pharma for the cost, but i suspect it is probably on borrowed time until it is knocked off its perch.
I think that the blog has been very clear about the potential problems associated with alemtuzumab, which as MD says may mean it's on borrowed time.
What's happened about the Coles Cambridge trial called CAMTHY when they are trying to prevent the autoimmunity problems associated with alemtuzumab?
where do you believe HSCT will fall in MS treatment chronology ? 2nd line or 3rd ?
It is currently third line, should it be first
I think there is risk in HSCT especially in the long long termHowever you have to look at what it can possibly do? And that is buy time not only to enjoy life at a better quality but also to give you guys chance to get the real cure and the real cause, I csnt believe after all these years, that people are still having to live with make do treatments rather than real cures, or shouldCynicism creep in with regards to how much money is being made by not finding a cure?
Gosh, reading these comments makes me wonder why Team G continues this blog. MSers are expecting miracles, blaming neurologists for their illnesses and oncoming disabilities.There is such a bad culture of entitlement. MS is incurable. We're told so from the get-go. We ought to ready ourselves for the worst but hope for the best. That way we wont be disappointed and angry.And Prof G, Stop telling people you can cure MS. you're CAUSING TROUBLE IN THE LONG RUN.
Dammed if you do, dammed if you don;t
"Gosh, reading these comments makes me wonder why Team G continues this blog. MSers are expecting miracles, blaming neurologists for their illnesses and oncoming disabilities.There is such a bad culture of entitlement. "I'm very puzzled by what you mean here. I've yet to meet someone with MS who blames their neurologist for ongoing disability. I'm sure there may be some, just as with everything in life, some people will always look to ascribe blame but that has little to do with MS per se. Nor do I understand your comment about a culture of entitlement, it sounds very Tory-esq to me and very far removed from the truth in the majority of cases. Nor have I read anything on this blog suggesting a cure is imminent but nor do I agree that this is not possible one day. If 'entitlement' to you is synonymous with not giving up then I'm sorry to hear this.
I think that MSers are entitled to the best treatment available, that some don't seem to be getting it is a source of great frustration to them and us. We're trying to ensure that this changes and the blog can and does influence this from what we hear behind the scenes.Rest assured than no-one in team G is giving up any time soon.
It seems HSCT would be of value for a subset of msers with highly active disease. I would choose this over Alemtuzimab easily if I fit this category. If this trial gets us closer at having this as an option, I'm all for it. However I suspect if the results show HSCT as superior it will not be approved as an option.I guess the question is what is necessary to get approval? You've said it yourself that pharma and the regulators have reached an agreement and I don't see how HSCT fits into this arrangement.
Not sure if it will be powered to show superiority or on-ineriority.Why is it necessary to get approval?…..payment for the procedure and importantly malpractise insurance for the neuro and maybe the rules
Put HSCT up to NICE and ask them to approve as a treatment. The literature is already out there from various studies showing it is more efficient than anything current available.Or do what most drug companies do and prove it is more efficient than a poor drug like interferon..
You have to go to MHRA/EMA/FDA first who is going to pay£30K to speak to regulators. Please tell me how this is done
Could crowd funding help with this? While its a year's wage for me I would have thought this figure would be quite achievable. I'd happily donate if it helps get HSCT on the map.
Is there a risk that if you use HSCT that all the drug companies will get annoyed as you are prescribing a treatment that doesn't need their expensive less effective drugs? Would not it be amazing to see a doctor work out… Hey, here is a really efficient treatment that could SAVE the NHS millions of pounds a year in drugs and follow up care.. Let lobby to get it in now. Will it ever happen????
Simple answer…probably not……its too difficult and costly. If someone knows how contact me
Brother, you sound exceedingly angry. Calm down and chew some Valerian root.
Frurstrated
I dont want to appear negative but i hope it spurs someone to prove me wrong
MD's – what is your honest opinion of HSCT.. Stop the disease and then see if one of your re-myelinating treatments or MSC's could help patients even further? Or do you bucket it in the same vane as CCSVI??
I see problems getting approval.It should stop relapsing MS but am not sure that it is the answer for progressionCCSVI has dubious science The logic of HSCT is clear and the data is already there for HSCT and if this is no good, you may as well chuck all other other drugs away as it is the ultimate immune reset. The question is how soon after diagnosis you should do this. The question is whether you have to be so aggressive or can you do the same with current treatments or other approaches, experimentally we can without the risks of HSCT.
We seem to need ZEUS desperately.
what you need is JESUS not ZEUS !
I'd love to see it available as a first line treatment. The previous polls run on here show massive interest. I start lemtrada next week. Given a choice I'd choose HSCT.
Anon, good luck with the Lemtrada. I had my first infusion 9 years ago and am doing well. The infusions (5 days and 3 days the second year) really were that big a deal. The main issue was boredom – take a good book. Wait six months after the infusion and then take a view on how you are doing – i think you'll find you made the right choice. I've had no relapses for 9 years and MRIs show no activity. I was classified as having "quite aggressive" rrms. Best wishes.
That's good to hear. Any problems such as Graves disease after your treatment?
How will ZEUS be different than the MIST trial if they include HSCT to the control arm ?
I think in the Mist trial, the comparator arm is any approved MS therapy. This new trial will be restricted to Alemtuzumab as the comparison.The Mist trial seems ambiguous since the comparator ranges from anything from Copaxone to Tysabri. The choice is up to the patient I believe.
I meant Alum !!
I've had HSCT myself, and I would love to take a neuroprotective now to cover off that aspect as well. There's almost certainly no harm in it, I'm willing to pay for it myself, the science is solid (and I accept it's not yet fully proven), and I'd sign any disclaimer to say the risk is on my head. Despite all this, can I access it in the UK? Like hell I can. And if I try, I'm treated with absolute disdain. The system is ridiculous.On a side note, having gone abroad for HSCT myself, I think it should be allowed in the UK on the same basis as the cancer treatments which they let through after Phase II, with a Phase III happening the real world (and license retracted if results appear to differ from the Phase II in a negative way).This is a serious, serious disease, and you have a relatively small window to do something about it to prevent the onset of disabilities, so access to treatment is time critical. Nobody has 10 years to wait for these trials to play out. If the evidence is there (and there's over 2 decades worth of trials for HSCT already), the stats and risks should be provided to patients, and let them decide what they want to do.I'd echo the point of Anon above in that neurologists really need a reality check and to grasp that what we want is to NOT BECOME DISABLED. This doesn't mean "I want to become only a bit disabled" or "I want to become disabled more slowly". If there is a treatment out there that offers even the slimmest chance of this, I want to take it. If there are risks involved in that, by all means educate me as to what they are, but those should be my risks to take. I don't want to be railroaded into a wheelchair because the etiquette of the medical establishment says it's the politically correct thing to do!My neurologist should be on MY side. Lay out ALL the options, no spin, no marketing, no politics just hard facts and figures. And let me make a choice as to what risks I'm prepared to wager against protecting my ability to walk/work/live a normal life.That's my view, anyway.
Have you got epilepsy, etc.
Well said Matt.
There has been talk of trying to change the licencing system, but what is the phase III…a registry?. Because if there is free access after phase II who would volunteer for a phase III when there is a chance they will not get the active drug?Next what is the end point going to be? Cancer can have quite a hard edge when it comes to outcome. Death rate catches he news,we often hear the body count but virtually never here figures of the injured. The problem is MS does not progress that fast…so what outcome measure do we use time to an EDSS point, brain volume change?MS Stat2 will cost a few millions for every million we could give 10,000 MSers a statin for a year, so for 5 million that's 50,0000 a year or 10,000 or5 years. To address the comment posted by anon 11.00 Do we ask every body to eat loads of fried eggs before getting their cholesterol checked:-) so they can get on a statin:-0
Isn't phenytoin and other such drugs approved for other uses for pain etc
phenytoin is an anti convulsant so anti epileptic however in our hands this is not the best neurprotectant it was used because you can give high doses quickly as time was of the essense and I think DrKapoor did a fanastic job recruiting people to optic neuritis trial in just over a week from symptom onset
Yeah very true regarding speed of itWhat is the best you guys believe and would your prescribe on a named patient basis etc
What do we make of conflicting reports into HSCT for PPMS and spms? Even Dr Burt who is adamant his treatment is for RRMS had previously had success treating spms, with lower edss and early in the disease
The science behind HSCT is firmly focussed as a treatment for RRMS, I would not recomend anybody undertaking the procedure until approved…so there you have the party line. I would especially say I would not recomend that progressive MSers pay for this procedure….there are risks and for many it will not have the benefit that you desire which is to halt and reverse progression. Will SPMSers and PPMSers benefit from this….I am sure the answer is yes as many progressive MSers have active disease but this is clearly not the answer to progressive ms unless it stops progressive ms materialising. I think there are otherways to achieve this aim.
"Other ways to achieve this aim"..great..realistically how long before they're available to the people that need it..??
You know the answer to this questions already because without the studies nothing can happen, so how long does it take…it depend on how much support you get.
What other ways are there to achieve this?It's easy to say we're getting there there's options etc but we have only one life one chance so we need answers and options now What do you do for rapidly orogressive Ms, surely there's an inflammatory and neurodegeneration aspect so Hsct and then a neuroprotective is the option?I've started with testosterone as its the lnly one I can access currently until someone gets another on the marketPlus yes there Harm in testosterone but it's longer term and if I can have 20 years of functioning I'd sign up right now
I did not say we are getting there, I said I believe there are other ways…these need to tried.If you have gadolinium enhancing lesions then a DMT/HSCT maybe an option, but the only option available is DMT, you want me to say yes go ahead try this or that but you know I need to sit on the fence.
Yeah l get that and we know it's impossible to be drawn on somethjng but your opinion is only that and not medical advice Appreciate it though
Do you?what you said Do you think of walking on a plank.its safe I say wont do you any harm actrr all it is two metres wideyou spend thousand quid to walk on a plankyou forgot to say plank was thirty metres up and you have one leg and a tremor and cant see.You fall and dieYour parent says MD said it was safe to walk on a plank
Hows the testosterone going so far? To me seems logical. A lot of people use ot to enhance sports performance! So if it does something to ms then it's got to be worth a shot! Excuse the pun!
Not really noticed anything yet but then it's at 5mg as opposed to 10mg initially and I thinkThey say it takes months to work, there are some differences which are common with testo but not for Ms that ive realised
I bet you've grown a wicked beard and a mean Adam's apple though!!
Beards pretty good Matt! My levels were within normal range but when you look at the range it caters for 18-70 year olds so you can have low levels for your age and be within range