Jan 9, 2023·edited Jan 9, 2023Liked by Gavin Giovannoni
I’m a person with MS who has recently been told by my consultant at NNUH (Norwich) that I must stop taking Tysabri - which has successfully treated my rapidly evolving RRMS for 8 years - because there is no safety data available regarding risks of PML in Tysabri patients post 6 yrs (I’m very low JCV+). I have been told that all they will offer me instead is Tecfidera and to wait for another disabling relapse before I’m allowed anything else. This feels like going backwards to me and leaving me open to certain relapse and disability. Would I be eligible for the trial? It’s a real worry that this is the advice I’m receiving in this day and age and that trials like this aren’t on the radar of our hospital or healthcare providers. I shall certainly spread the word amongst my community.
Re: "because there is no safety data available regarding risks of PML in Tysabri patients post 6 yrs (I’m very low JCV+)"
This is not is correct. There are patients who have been on Natalizumab for well over 10 years. In our centre we continue Natalizumab in patients with a low index, but switch them to 6-weekly infusions (extended interval dosing). If we do switch we now tend to switch to anti-CD20 therapy (ocrelizumab or ofatumumab) to prevent rebound disease activity.
Thank you so much for this information. It’s really helpful and encourages me to go back and ask my consultant to consider these other options, especially to prevent rebound activity. I’ve been approached for advice on this by other patients in a similar position so will share with them. Your blog is invaluable. Thank you.
No you would not be eligible for the STAR-MS trial. To be eligible you would have to have disease activity on natalizumab, I..e it would have to failing you.
This would exclude a lot of potential people from the trial. Natalizumab is an extremely effective drug so you don’t have many people showing disease activity on it. I had high JCV titres so my consultant wanted me to come off it. I was offered all of the other drugs on the STAR MS trial but told that I didn’t qualify for HSCT so like so many others I paid to have the treatment abroad. I don’t understand the logic in qualifying for other drugs like Lemtrada with all of its side effects but not qualifying for HSCT.
A heads-up: I am reading alemtuzumab papers this week to raise a "smartish" question on anti-drug antibodies. Please expect an email with charts from me before the end of the week.
As someone who was severely disabled by undiagnosed and untreated MS for a long time, due to gross medical negligence (gaslighting), I don't think this applies to me. I think this is about people who are diagnosed and treated when they develop MS? You could only cure me if you undid the damage MS has done to me, so the myriad symptoms go away, I am no longer disabled, and I get my brain back ('significant cerebral atrophy'). Please do find a cure for that!
No! I think it’s exciting to think outside the box. You are making connections that just might make this disease curable. Like other trials and DMDs, this wouldn’t be for me, but there are many of us who didn’t have much choice. I say go for it! And thank you, as always.
Any experiences to share with us about the risks and benefits of alemtuzumab vs. AHSCT? Was your HCP comfortable with you taking on the risk of alemtuzumab treatment?
HCPs looking after pwMS on the NHS don't control the budgets. High-cost drugs are paid centrally by NHSE. AHSCT is relatively cheap, I.e. £28,000-£30,000 as a one-off upfront cost. The other high-efficacy DMTs are in the region of £18,000/year.
I have been listening to this podcast and would like to share my experience and my story, I find the fact there is a faction of MS neurologists do not look on AHSCT as a major choice extremely frustrating. I had to fight really hard agains my initial neurologist to get a referral to Sheffield for the treatment. Even though I knew I fulfilled the criteria.
The treatment has changed my life!
Before I had the treatment I was struggling to function day to day due to fatigue, getting up to go to the toilet was difficult and I would have had to give up work. The driving force in my life was to get AHSCT as I saw this as the best hope I had. I had also seen my father die through MS in 2009 and I was following a very similar tradgectory which meant I was prepared to accept the risks. (which are massively misrepresented). I became eligible for the treatment when I has an immune reaction to Tysabri.
The next question is has it worked?
The answer to this is yes I am now more active, cognitively I have completely retrained as a cloud architect and have been working full time for the last 12 months. This is something I could not have comprehended before the treatment.
Has my disability got better?
I am waiting on my new EDS score however I spent 5 years not being able to use my core. I have now managed to reenguage my core muscles and am learning to walk by not carrying all my weight through my shoulders. This is through being extremely regimented about doing Pilates and Physiotherapy and I now can use my core and my walking is improving slowly.
Given the option again would I have the same treatment.
Yes! It has not been easy but the alternative is a lot more difficult.
Thanks a lot for your informative posts! It's a sources of valuable information for patients beyond the UK too. Fourth months ago I had HSCT (Cy+ATG). Unfortunately after the hospital I got an infection and my EBV titre went very high for a couple of days (PCR value 23 000 UI). Does it mean that my new T and B cells were reinfected with EBV and if so, could it, in your view, jeopardize the treatment (I afraid it did and am considering a second tentative given that the treatment itself went well with zero side effects).
EBV reactivation is quite common after HSCT and at present we don't know if it affects outcome. EBV reactivation may have the opposite effect and act as a natural vaccine and stimulate immunity that then keeps the virus under control. In addition, we don't know if it is a mutated EBV that causes MS and the EBV that reactivates may be the non-mutated version. As you can see there are many unanswered questions.
I have been following your posts about smouldering MS, the role of microglia, and about the large interest in BTK inhibitors in MS. That is, I have tried to understand HSCT in relation to fig 3 in your 2022 paper! There is usually much focus about how HSCT affects the adaptive immune system, but I have not seen anything on the innate immune system, though I assume this is also reconstituted. Do you know if BTKi are relevant for patients who have been through HSCT?
If HSCT stops smouldering MS over decades, I would probably not mind if you said to me it was a cure, but I would also appreciate it if you added something like "or at least stops MS for the next X decades into the future". If I have pneumonia, antibiotics could cure it, but I might get it again at some later time in the future - not sure if that analogy works, though...
I was refused access to the STAR-MS trial on the basis that I have had MS for more than 10 years (even though I didn't get a diagnosis from a doctor till 2017). Has that criteria now changed? I did the screening tool and it wasn't asked.
I still keep wondering whether I could have convinced one of the doctors in charge of STAR-MS that I'd had MS less than 10 years as I didn't have a diagnosis. Or would they have read my medical records and seen that I very obviously did? It would be easier for me to accept if there was nothing I could have done.
Regarding improving T cell response to EBV, have you considered micro dosing Rapamycin? The data shows it improves vaccine response in people with diminished immune systems(basically reversing the clock). Peter Attia takes Rapamycin for it's general health benefits, maybe it's time for an N of 1 experiment.
Unfortunately in Australia we can’t get aHSCT until we fail 3 DMTs
My main concerns with it are
What is the best protocol? There are a few (aHSCT BEAM etc) and which one is most effective. What is the data on each?
What is the optimal age to start. Eg I’ve seen some do aHSCT at late 30s or 40s and it fails them
Is that a cure? Probably not. Maybe long term remission would be a better term
Also some lax lyrical without really discussing the risks : infertility, secondary auto immune diseases, Covid risks and infections etc
If you are a 29 year old woman does it make sense to get this treatment with the risk of infertility?
What about with Covid and significant risk of infection leading to fatalities.
What centres are the best?
Compare that to say ocrevus or Tysabri. You know the protocol is the same everywhere. You monitor specific risks but that’s it. The experience of Tysabri in the UK, or Australia or the US is the same whereas it differs wildly with aHSCT
I’d love this to be the silver bullet and even my neuro said this would probably be the most effective treatment in our first meeting almost 2 years ago. But alas we don’t offer it first line and I don’t have the cash to go Russia or Mexico during a pandemic.
I would have leapt at the chance to get HSCT in this country as part of a clinical trial, instead of having to pay for it to be done abroad. For me it’s been well worth the money because not only have I been in remission for 4 years but I have virtually no MS symptoms now, which is quite amazing considering that the right side of my body was progressively becoming weaker and when I relapsed I spent months at a time in a wheelchair. The only problem with the word “cure” is that everyone would expect these improvements.
💰Forty thousand American dollars bought me my legs and my life back, and I had five years of bliss. 💪Stem cell is amazing! Twenty five years ago I was diagnosed with MS. After a fairly aggressive beginning I decided to be a pioneer and try stem cell. I opted not to do chemo at the time and was told I’d likely need a booster. When I eventually relapsed, the Israeli clinic I went to had increased prices to $100 000, so I begrudgingly took lemtrada (but it has served me well other than a few pesky side effects). I believe stem cell or whatever they are calling it now is the best and safest chance of a cure for anyone with MS. And anyone who has the opportunity to have it would be doing themselves a huge disservice and quite literally destroying their lives by not doing it. This trial being offered is a dream opportunity not to be wasted. It’s about time stem cell is recognised as a first-line treatment and a cure for the most devastating cruel disease. And yes, all those involved in the industry will be out of a job and the drug companies will lose billlions. But hey, people will have their lives back!
Thank you for your informative articles that give hope intertwined with data. Wanted to PM this question but - wisely- you don’t give that option. Question: Have you or your colleagues looked at complementary healthcare for MS? Curious about this study: 👇🏼
Thank you for this. I am trying to get a Facebook account with little success (I may have had one years ago and suspect I didn’t close it down properly etc). I will keep trying.
I’m a person with MS who has recently been told by my consultant at NNUH (Norwich) that I must stop taking Tysabri - which has successfully treated my rapidly evolving RRMS for 8 years - because there is no safety data available regarding risks of PML in Tysabri patients post 6 yrs (I’m very low JCV+). I have been told that all they will offer me instead is Tecfidera and to wait for another disabling relapse before I’m allowed anything else. This feels like going backwards to me and leaving me open to certain relapse and disability. Would I be eligible for the trial? It’s a real worry that this is the advice I’m receiving in this day and age and that trials like this aren’t on the radar of our hospital or healthcare providers. I shall certainly spread the word amongst my community.
Re: "because there is no safety data available regarding risks of PML in Tysabri patients post 6 yrs (I’m very low JCV+)"
This is not is correct. There are patients who have been on Natalizumab for well over 10 years. In our centre we continue Natalizumab in patients with a low index, but switch them to 6-weekly infusions (extended interval dosing). If we do switch we now tend to switch to anti-CD20 therapy (ocrelizumab or ofatumumab) to prevent rebound disease activity.
Thank you so much for this information. It’s really helpful and encourages me to go back and ask my consultant to consider these other options, especially to prevent rebound activity. I’ve been approached for advice on this by other patients in a similar position so will share with them. Your blog is invaluable. Thank you.
No you would not be eligible for the STAR-MS trial. To be eligible you would have to have disease activity on natalizumab, I..e it would have to failing you.
This would exclude a lot of potential people from the trial. Natalizumab is an extremely effective drug so you don’t have many people showing disease activity on it. I had high JCV titres so my consultant wanted me to come off it. I was offered all of the other drugs on the STAR MS trial but told that I didn’t qualify for HSCT so like so many others I paid to have the treatment abroad. I don’t understand the logic in qualifying for other drugs like Lemtrada with all of its side effects but not qualifying for HSCT.
I really feel for you Kelly I'm at NNUH and find them very behind the times and it is extremely frustrating. Hope you keep well xx
A heads-up: I am reading alemtuzumab papers this week to raise a "smartish" question on anti-drug antibodies. Please expect an email with charts from me before the end of the week.
Do you think it is irresponsible to discuss MS as being a potentially curable disease?
As someone who was severely disabled by undiagnosed and untreated MS for a long time, due to gross medical negligence (gaslighting), I don't think this applies to me. I think this is about people who are diagnosed and treated when they develop MS? You could only cure me if you undid the damage MS has done to me, so the myriad symptoms go away, I am no longer disabled, and I get my brain back ('significant cerebral atrophy'). Please do find a cure for that!
No! I think it’s exciting to think outside the box. You are making connections that just might make this disease curable. Like other trials and DMDs, this wouldn’t be for me, but there are many of us who didn’t have much choice. I say go for it! And thank you, as always.
Any experiences to share with us about the risks and benefits of alemtuzumab vs. AHSCT? Was your HCP comfortable with you taking on the risk of alemtuzumab treatment?
I am really not a massive fan of guest posts but would be happy to write down my experience if it helps with your recruitment efforts?
But I need to finish reading (and understanding/codifying) this first: https://www.frontiersin.org/articles/10.3389/fimmu.2020.00124/full
Re: "I am really not a massive fan of guest posts but would be happy to write down my experience if it helps with your recruitment efforts?"
Yes, please we need the MS community to get behind this study.
I owe you this much at the least. Will get back to you with a draft in a few days.
Re "We are finding that most MS Teams are not even discussing certain DMTs at AHSCT at their MDT (multidisciplinary team) meetings. "
Not sure how the NHS works, but could this be for budget reasons?
Does anybody by chance monitor the costs of treatments prescribed by MS teams? Is there an allocated budget for MS DMT prescription?
If that be the case, just a few patients on high cost treatment could blow up the whole budget
HCPs looking after pwMS on the NHS don't control the budgets. High-cost drugs are paid centrally by NHSE. AHSCT is relatively cheap, I.e. £28,000-£30,000 as a one-off upfront cost. The other high-efficacy DMTs are in the region of £18,000/year.
I have been listening to this podcast and would like to share my experience and my story, I find the fact there is a faction of MS neurologists do not look on AHSCT as a major choice extremely frustrating. I had to fight really hard agains my initial neurologist to get a referral to Sheffield for the treatment. Even though I knew I fulfilled the criteria.
The treatment has changed my life!
Before I had the treatment I was struggling to function day to day due to fatigue, getting up to go to the toilet was difficult and I would have had to give up work. The driving force in my life was to get AHSCT as I saw this as the best hope I had. I had also seen my father die through MS in 2009 and I was following a very similar tradgectory which meant I was prepared to accept the risks. (which are massively misrepresented). I became eligible for the treatment when I has an immune reaction to Tysabri.
The next question is has it worked?
The answer to this is yes I am now more active, cognitively I have completely retrained as a cloud architect and have been working full time for the last 12 months. This is something I could not have comprehended before the treatment.
Has my disability got better?
I am waiting on my new EDS score however I spent 5 years not being able to use my core. I have now managed to reenguage my core muscles and am learning to walk by not carrying all my weight through my shoulders. This is through being extremely regimented about doing Pilates and Physiotherapy and I now can use my core and my walking is improving slowly.
Given the option again would I have the same treatment.
Yes! It has not been easy but the alternative is a lot more difficult.
This is terrific news! I’m very happy for you.
Great to hear this. Thanks for sharing.
Dear Prof Gaving,
Thanks a lot for your informative posts! It's a sources of valuable information for patients beyond the UK too. Fourth months ago I had HSCT (Cy+ATG). Unfortunately after the hospital I got an infection and my EBV titre went very high for a couple of days (PCR value 23 000 UI). Does it mean that my new T and B cells were reinfected with EBV and if so, could it, in your view, jeopardize the treatment (I afraid it did and am considering a second tentative given that the treatment itself went well with zero side effects).
Thanks in advance for your opinion.
EBV reactivation is quite common after HSCT and at present we don't know if it affects outcome. EBV reactivation may have the opposite effect and act as a natural vaccine and stimulate immunity that then keeps the virus under control. In addition, we don't know if it is a mutated EBV that causes MS and the EBV that reactivates may be the non-mutated version. As you can see there are many unanswered questions.
I have been following your posts about smouldering MS, the role of microglia, and about the large interest in BTK inhibitors in MS. That is, I have tried to understand HSCT in relation to fig 3 in your 2022 paper! There is usually much focus about how HSCT affects the adaptive immune system, but I have not seen anything on the innate immune system, though I assume this is also reconstituted. Do you know if BTKi are relevant for patients who have been through HSCT?
If HSCT stops smouldering MS over decades, I would probably not mind if you said to me it was a cure, but I would also appreciate it if you added something like "or at least stops MS for the next X decades into the future". If I have pneumonia, antibiotics could cure it, but I might get it again at some later time in the future - not sure if that analogy works, though...
Re: "BTKi are relevant for patients who have been through HSCT"
No. BTKi are still in phase 3 so they have not been tested post HSCT. However, there is a rationale for testing BTKis post and induction therapy.
I was refused access to the STAR-MS trial on the basis that I have had MS for more than 10 years (even though I didn't get a diagnosis from a doctor till 2017). Has that criteria now changed? I did the screening tool and it wasn't asked.
No that is still and exclusion criteria. It is from symptom onset not diagnosis.
I still keep wondering whether I could have convinced one of the doctors in charge of STAR-MS that I'd had MS less than 10 years as I didn't have a diagnosis. Or would they have read my medical records and seen that I very obviously did? It would be easier for me to accept if there was nothing I could have done.
Regarding improving T cell response to EBV, have you considered micro dosing Rapamycin? The data shows it improves vaccine response in people with diminished immune systems(basically reversing the clock). Peter Attia takes Rapamycin for it's general health benefits, maybe it's time for an N of 1 experiment.
Unfortunately in Australia we can’t get aHSCT until we fail 3 DMTs
My main concerns with it are
What is the best protocol? There are a few (aHSCT BEAM etc) and which one is most effective. What is the data on each?
What is the optimal age to start. Eg I’ve seen some do aHSCT at late 30s or 40s and it fails them
Is that a cure? Probably not. Maybe long term remission would be a better term
Also some lax lyrical without really discussing the risks : infertility, secondary auto immune diseases, Covid risks and infections etc
If you are a 29 year old woman does it make sense to get this treatment with the risk of infertility?
What about with Covid and significant risk of infection leading to fatalities.
What centres are the best?
Compare that to say ocrevus or Tysabri. You know the protocol is the same everywhere. You monitor specific risks but that’s it. The experience of Tysabri in the UK, or Australia or the US is the same whereas it differs wildly with aHSCT
I’d love this to be the silver bullet and even my neuro said this would probably be the most effective treatment in our first meeting almost 2 years ago. But alas we don’t offer it first line and I don’t have the cash to go Russia or Mexico during a pandemic.
Useful podcast Prof G, you're certainly raising awareness of the trial.
Thank you for letting everyone know about this.
Karen
I would have leapt at the chance to get HSCT in this country as part of a clinical trial, instead of having to pay for it to be done abroad. For me it’s been well worth the money because not only have I been in remission for 4 years but I have virtually no MS symptoms now, which is quite amazing considering that the right side of my body was progressively becoming weaker and when I relapsed I spent months at a time in a wheelchair. The only problem with the word “cure” is that everyone would expect these improvements.
💰Forty thousand American dollars bought me my legs and my life back, and I had five years of bliss. 💪Stem cell is amazing! Twenty five years ago I was diagnosed with MS. After a fairly aggressive beginning I decided to be a pioneer and try stem cell. I opted not to do chemo at the time and was told I’d likely need a booster. When I eventually relapsed, the Israeli clinic I went to had increased prices to $100 000, so I begrudgingly took lemtrada (but it has served me well other than a few pesky side effects). I believe stem cell or whatever they are calling it now is the best and safest chance of a cure for anyone with MS. And anyone who has the opportunity to have it would be doing themselves a huge disservice and quite literally destroying their lives by not doing it. This trial being offered is a dream opportunity not to be wasted. It’s about time stem cell is recognised as a first-line treatment and a cure for the most devastating cruel disease. And yes, all those involved in the industry will be out of a job and the drug companies will lose billlions. But hey, people will have their lives back!
Finally a heartfellt post about Hsct
For all the zealots that want to heard
Congrats
Not a fan of aHSCT I take it
NHS Scotland are giving me novatrone there saying to me ahsct is to dangerous there both chemotherapy treatment
Thank you for your informative articles that give hope intertwined with data. Wanted to PM this question but - wisely- you don’t give that option. Question: Have you or your colleagues looked at complementary healthcare for MS? Curious about this study: 👇🏼
https://www.sciencedirect.com/science/article/abs/pii/S2211034822009713
Dear Mindy
Would you be kind enough to point me to the forum please? Thank you.
Thank you for this. I am trying to get a Facebook account with little success (I may have had one years ago and suspect I didn’t close it down properly etc). I will keep trying.
Hi Mindy, I have got into Facebook and waited a few days to be accepted into the two groups, are you able to nudge them your end? Thank you.