From the horse’s mouth

The following is an online presentation from Prof. Richard Burt on their latest HSCT results. His presentation was embargoed until today. Enjoy.

When I was asked whether or not these are the most important trial results I have seen in the MS space. What do you think I said?

31 thoughts on “From the horse’s mouth”

  1. Why was the DMT group so poor, so absolutely garbage in their disease progression and relapse percent? How can rebif in the ocrevus trial be 15.2% for 96 weeks (maybe 10% at 60 weeks), and here be nearly 80%?? What were they giving these patients? How can the editors not make them publish a huge asterisk after the data to say “well yeah, we were pretty poor at dividing our initial patients into our groups?”

    Can you plainly state what you think of the results, considering that at least 21 patients were on tsyabri in this trial (what was their breakdown? How could they be this bad at 5 years? what was their resulting disease progression and lesion formation?)

  2. “I have zero ,none,pharmaceutical suport”

    “There has never had been”(suport)

    “We where limited to hematologic journals (between 1995 and 2009) there was no interest from the neurology community”

    “Finally in 2009 we reported a paper in Lancet neurology”

  3. “I have zero ,none,pharmaceutical suport”

    “There has never had been”(suport)

    “We where limited to hematologic journals (between 1995 and 2009) there was no interest from the neurology community”

    “Finally in 2009 we reported a paper in Lancet neurology”

  4. Also the new layout of the blog is not as good as the old layout. Posts are not arranged as a timeline- I did not see the post by mousedoc about the HSCT trial until I scrolled far down on this post- it never appeared for me on the front page. I also see that the three other posts listed as “read more” are not listed at all on the front page- Food Coma, Smouldering MS, and How to Manage RRMS have all disappeared off of the front page. Instead, I see posts from over a week ago- it is confusing and makes navigating time consuming as I fear I have missed posts. There is no listing of posts by time on the left anymore- it is buried inside the hamburger. Also, the large text means I cannot quickly scan through the posts and ignore or highlight posts I’d like to see. It takes up too much space on my phone. Just my opinion

    1. Chris, there is a list of recent posts in the drop-down menu on the right. You can also swipe left and right to move between posts in chronological order. If you are on a PC and using a mouse as soon as you move the cursor left or right of the main page at the tope a large arrow appears that allows you to move through the posts in chronological order.

  5. Hugely exciting. I am guessing you will say the results are very impressive – and possibly game-changing for the MS world. So pleased it looks like HSCT works incredibly well for those with highly relapsing MS. Any chance it might eventually be considered as a treatment for those of us with RRMS – but who have fewer relapses?
    Rachel Horne

      1. Very ironic indeed. What is the point of a drug that stops relapses but does nothing to go into spms when I believe spms is there all along…….

  6. Hi Dr. G, Wheelchair Kamikaze here. Congrats on the new blog, I wish you much success with it.

    In regards to the presentation by Dr. Burt, he reiterates his old mantra of “no inflammation, no results”. However, in the slide comparing the RRMS results with those achieved in early SPMS patients, it’s clear that the SPMS patients achieved EDSS stability over the course of five years. While this isn’t the same as the improvement seen in the RRMS patients, isn’t the cessation of progression in early SPMS patients something of an achievement in and of itself?

    I’m just wondering if, by focusing solely on the improved EDSS scores of the RRMS patients, Dr. Burt and other HSCT practitioners aren’t missing the forest for the trees. Any progressive MS patient would certainly take stability over the insidious, ongoing progression they are forced to suffer through. Geez, what I would give for five years of no progression…

    It’s a shame that we aren’t seeing any trials of HSCT on progressive patients. Thoughts?

    1. I am glad you saw this diamond. Yes, HSCT does work in progressive MS it just takes longer to see the effects and they are less obvious. This is related to reduced reserve, lag, etc. that is all captured in our length-dependent axonopathy hypothesis. Yes, in the UK we have been discussing doing a progressive trial for exactly these reasons. The downside is the risks and that some MSers tolerate the chem poorly.

    2. “HSCT has seen some very positive results, but it is an aggressive treatment. This means it comes with high short and long-term risks and complications. These include:

      – an increased, long-term risk of developing infections
      – an increased risk of developing cancer and autoimmune conditions, such as thyroiditis
      – early menopause
      – fertility problems.

      “The chemotherapy has its own side effects too. These include an increased risk of bleeding and bruising, fatigue, loss of appetite and hair loss.

      “For people with a higher level of disability before the transplant, chemotherapy can also do more harm than good. Chemotherapy treatments can lead to a further loss of mobility and worsened neurological function.”–what-to-expect

      As someone with long term, slow PPMS, I would not consider HSCT, nor indeed any form of immune system destruction. I do not believe this to be the answer for PMS. I fear research into MS becoming increasingly corralled into this route of therapy.

  7. Thanks for that. 2 questions if I may:

    1) Alemtuzumab on the side, why would patients stay on Tysabri or Fingolimod if we know that they will progress to SPMS?
    Are they not better off heading towards HSCT instead while they are still in the earlier stages of their disease?

    2) Does HSCT normalise brain atrophy rates?

  8. This is very interesting. I wonder how Hstc compares to Cladribine . I new DMDs do not stop ms. I personally was on Fingolimod 7 years from diagnosis which although stopped relapses did nothing to stop progressing.

    How Hstc and cladribine compare to transitioned from Rrms to Spms?

    Wheelchairkamikaze I like your observation


  9. I can certainly see why many PwMS will/would opt for HSCT.

    For me personally, with longstanding, slow PPMS, I would have far more fear of the neurotoxicity of chemo than any possible benefit. And is one not left with an “aged” immune system after treatment, meaning that there are long term risks?

  10. Dr. Richard Burt is a physician that all physicians should aspire to be. He has not “sold his soul to the devil” as many others have.

    It tells that HSCT is very safe with zero deaths and should be utilized a lot more and a lot earlier. It is too bad it is used only for < 5% of the RRMS population right now with highly active disease not responsive to current DMDs.

    It tells me that the term HSCT is misleading in that stem cells play a very small part of it and are only needed to repopulate our immune system earlier to prevent infection.

    It is the chemotherapy part of the protocol, cyclophosphamide I believe, that is outperforming all the other DMD drugs by a landslide (minus alemtuzumab and ocrezulimab). The DMDs looked at perform dismally, including natalizumab, fingolimod and DMF.

    It also tells that the current immunotherapies are definitely not the answer to stop and reverse progressive disease. The researchers, secondary to financial backing of pharma, are "barking up the wrong tree" for treating progressive disease for years.

    While "possibly" slowing progression of the disease, a progressive patient will end up with the same disastrous inevitable clinical outcome in the long run.

    For researchers, neurologists, pharma, steering committees and governing bodies to willfully ignore meaningful treatments of progressive disease (neuroprotection, remyelination and neurorestoration ) for the last 1/4 century will not be remembered kindly in history.

  11. I hope that publication of the results of this trial will force the medical establishment to begin offering HSCT more widely.

    It is clearly and indisputably the most effective treatment for MS currently available.

    Had I had the opportunity to consider aHSCT when I was diagnosed, the treatment would have been easier on me and I might now be active and working instead of dealing with (a thankfully now stable) edss of 6.5 which has destroyed my life.

    It’s time for medics to stop being complacent with the “wait & see” approach. There is no longer any excuse for waiting to see just how bad MS symptoms can get before offering a treatment which demonstrably works, is much cheaper and has a better safety profile than the significantly less effective drugs which are dispensed like smarties.

    PEOPLE with MS are not statistics. We have (or had) lives and deserve better. There is no longer any need for 85% of those with RRMS to develop SPMS. It can be halted early, preventing years of pain and distress for tens of thousands of people in the UK.

    We need support from neurologists, haematologists and the NHS. We need to have a voice and to be listened to.

    To the Doctors on this forum, I have a question. If it was yourself or your child with a new diagnosis of MS, what treatment would you choose and when ?

    1. Dear Phoenix2507 Thanks for your comment. I couldn’t agree with you more; the ‘wait & see’approach belongs to the dinosaurs. The problem we have is that HSCT is still only offered as a 2nd/3rd line therapy under the NHS. To move it to 1st-line we probably need to do a trial of say HSCT vs. Alemtuzumab and/or ocrelizumab and/or natalizumab.

      I hope you realise that at Barts-MS we are very supportive of your perspective, but our hands are tied by strict NHS England guidelines.

      1. I am so pleased to hear that Prof G.
        I am fortunate to have had HSCT but I regret that it wasn’t sooner and I am furious that the complacent approach of my neurologist meant that nothing was done for me until I took control of my treatment plan and made it happen.
        I was able to research and am tenacious, but many people aren’t and few are able to fundraise for private treatment.
        Part of the problem is also that nationally the neurology & haematology disciplines need to be working together on this. The ABN needs to give clear direction.
        Whilst the powers that be are stopping clinical excellence, people are suffering and lives are being ruined. When there was no treatment I can understand, but now there are published results for a treatment that is cheap, effective and very easily available.
        What process has to happen in order to make it generally accessible ? I don’t understand why it can’t be when it is carried out in the nhs at Kings and Hammersmith and privately at London Bridge. Why can it not be extended.

      2. Thank you Prof G.
        I don’t understand why it isn’t offered generally when Imperial College are already doing so. It is available privately at London Bridge too, so it can’t be a clinical issue.
        CQCs could save huge amounts of money from DMDs that are no longer needed month on month.
        Who has to push this so that others don’t end up in the same position as me – unable to work, struggling by on disability benefits, and unnecessarily disabled.
        I ran my own business, was contributing to the economy, employed other people. Now I am forced to spend 80% of my time in bed ! No one should live like this when there is a treatment that can kick it into remission for the majority.
        There is no need for it to take years, that will be too late for thousands of others who can live their best lives, given the chance.
        Whilst it too late for me to recover the existing damage, I hope that my current remission is permanent. I have to do all I can to help others avoid ending up like me.
        I would like to understand what the barriers are that have to be overcome to get this accepted by the NHS. It is already being done and Dr Burt’s trial has compared it to DMDs. That is the point.
        In addition DMDs are only followed up in trial for 2-3 years and the HSCT trial exceeds that. So why is it not good enough. Who has to approve it ?

      3. So ‘would I like to understand what the barriers are that have to be overcome to get this accepted by the NHS’. The adoption of innovations is a slow and complicated process. One of the reasons why we run this blog and are so heavily engaged in MS education is help drive adoption of innovations. However, what we can do is only a drop in the ocean of what is required to achieve real behavioural change.

    2. I couldn’t agree with you more! I went to Sheffield 2 years ago walking with a walking frame very difficult, i was denied stem cells (thanks for that) i wouldn’t fit protocol i continued with crap fingolimod went rapidly downhill stuck now on a wheelchair unable to walk /stand up with carers 3xday. Taken Cladribine i think it has slowed things down i must THANK Barts for that. I still wondered how less i would have progressed had i had the stem cells, you said it we are numbers to many doctors. A change must happen.

  12. I’m really excited to see this approach gathering pace. Alemtuzumab has done a great job for me from an MS perspective but I’ve had 3 new autoimmune issues crop up afterwards, so I wonder if HSCT protocol like this might not be a future option should I need it.

    However, it also occurs to be that by selecting people with such active disease they have really stacked the trial to produce eye catching results. Things like the changes in lesion volume seem like they could be heavily influenced by the combination of such strong anti-inflammatory treatment and the natural regression to the mean that occurs as lesions disappear during remission. Similarly with regards to edss scores etc, how much of this is the product of a regression to the mean once inflammation is switched off? The much more modest results seen in progressive disease would fit with this as well.

    Is this a fair assessment?

    1. The reason why HSCT does not work as well as in SPMS and PPMS is timing and the same reason why all DMTs are less effective. If you have accumulated enough damage prior to HSCT that damages then drives worsening that is independent of focal inflammation, etc. The message is we have to treat MS effectively and early. You don’t have to use HSCT to achieve this; HSCT simply gives you a greater chance of getting on top of the disease cascade.

      1. Thanks for that – I’ve read that post a few times now, it’s excellent.

        I’m in the position now where I’ve had 5 years of NEDA in terms of new clinical symptoms, relapses, and MRI changes (with atrophy apparently in normal range for my age). But the amount of damage present on the scan has been extensive from first diagnosis, so it is concerning to wonder how much has been primed for the future.

        I’m hopeful that perhaps whatever damage there is has healed well and that being well for such a long stretch is indicative of a positive outlook. It’d be nice if better measures like neurofilament etc. became widely available so I’m not having to guess at what’s going on below the surface though!

      2. Unfortunately, there is little we can to treat previous damage. What you need to do is now practice a brain-healthy lifestyle and to avoid getting co-morbidities. The latter is to maximise your outcome over your lifetime. Hopefully, in the future, we will have add-on treatments to prevent ongoing and delayed neuroaxonal loss and treatments to restore function.

      3. “with atrophy apparently in normal range for my age”

        May I ask which DMT you have been taking for the last 5 years?

  13. I was NEDA on tecfidera for a year and half, then moved to alemtuzumab then three and half years ago. Not sure they are being properly disciplined in how atrophy is being monitored, but that was the commentary on the reports.

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