Nov 4, 2023·edited Nov 4, 2023Liked by Gavin Giovannoni
Daughter diagnosed in 2019 with RRMS, aged 15.
IRTs were not discussed and we had no knowledge of them although we were convinced the ‘hit it hard early’ was the way to go.
Mum had MS and we were too familiar with the consequences of being under treated.
She started on Dimethyl Fumarate but did move on to Ocralizumab after 12 months.
Our research led us to believe HSCT would bring her the best long term outcome. Her paediatric neurologist was supportive of our opinion but aside from considering other criteria age was a factor.
A few months after turning 18 she was approved for treatment under Dr Kazmi. Unfortunately not NHS funded due to no new lesions on MRI but other factors pointed towards a less favourable long term outlook (heavy lesion load/age at diagnosis/lesion location).
She is now almost 3 months post transplant and doing well.
She’ll be involved in a Q&A session along with 3 others discussing their experience of HSCT at the AIMS Summit at the end of the month.
Being just 19 she is keen to share her perspective on her experience in the hope that others young people in similar situations become aware of their options. (Not named on the programme as only recently been confirmed)
After careful consideration she took the decision to go through fertility preservation treatment as she considered the risk of infertility too high to leave to chance.
The more I read your newsletter, the more I realize my fear and lack of knowledge has not served me well. I like to think of myself as smart, but MS has pushed me to a level of denial that I am astonished at. Denial and some early trauma related experiences that have contributed to my "toughing" it out on my own, not believing I deserved to receive help etc. I am now looking at Cladribine - 61 years old with increasing progression in the last 4 years, - if this can help me stabilize into the future, I think it is time to advocate for myself and begin a treatment, better later than never. It is so hard for me to contact my neurologist to ask for this potential, which is bananas, but there ya go. A giant, heartfelt thank-you for all you do.
Lastly, how does on measure the MRI metrics of brain volume loss 'reversal' or arrest since we do NOT measure volumetric analyses in 99% of clinics worldwide ???
Thank god in 2015 my daughter aged 17 had the option of lemtrada … 3 months after diagnosis . Normal life since , stable MRI x 8 she now works in NHS , keep fighting the good fight Prof Giovannoni , for the cures and risky treatments , patients need to choice .
As a person who has been treated with Alem, I’m not able to concur with Doc Avasarala. Lots of cancer treatments, among others, are ‘laced with severe side effects’ but are utilised in the care of patients. I can’t say categorically, but understand that the majority of people who seek to end their lives at centres such as those in Switzerland have neurological conditions. Secondly, NHS England data from some 10 years ago, states that the average age of death for PwMS is 66 and that 73% die under the age of 75years. Now in anyone’s book they’ve got to be mighty good reasons to hit MS early and hard, and this doesn’t take account of the challenging job of living with this disease!
I’ve previously joked that ProfG can be vulnerable to being all doom and gloom, as I’ve been so far in this comment, but I do know that I’m currently not depressed or too horribly disabled due to enjoying a good quality of life and having done so for the past six years, thanks to receiving Alem.
I was a month from my 51 birthday when I was diagnosed and the neuro told me I’d likely had MS for years, which reflecting back, I think is probably the case. The subsequent neuro told me that I wasn’t eligible for anything stronger than dimethyl fumarate, exclaiming to me the escalation model (as if this were the only approach to treatment) Thank goodness I’d discovered the Bart’s MS Blog, ProfG vids on YouTube and the guidelines on DMTs by the ABN! After sending a couple of strongly worded emails I was referred to a centre in London and a month before my 52 birthday began my first round of infusions.
The delay caused by this resulted in a second relapse in six months and cost me the use of legs for walking any more than a mile/2 on a good day and I do have some balance issues, quite a lot of pain and some fatigue and cog fog, but, and it feels like a Very Big But, I’ve not deteriorated since the treatment finished in 2017. Now a month from my 60th birthday I’m clearly no spring chicken and I don’t think I was treated early after disease onset, I do however think Alem, for all the associated risk factors, can be ‘life saving’ Treatment with it should be on a person by person basis and any PwMS precluded from receiving it should be based on their health status and not on the risks - these can be managed, primarily through quite rigorous monthly monitoring for four years.
As well as being a strong proponent of flipping the pyramid and use of Alem and ASCT ProfG, as we all know, promotes healthy living too and I wonder if choosing to do this has assisted with my levels of well being since treatment. I would certainly endorse ProfG position on this.
I would always advocate those who are newly diagnosed to learn all about DMTs, their rights as patients, about eligibility criteria and to push for the most effective treatment they can get and that their if their neuro refuses treatment on flimsy or erroneous grounds then ask to be referred to another neuro - preferably one like ProfG who work to flipping the pyramid.
ProfG concerning the ‘cure’ word: I remember reading something you’d written during the past eight years that said ASCT and Alem should be considered in terms of achieving ‘remission’. You explained that a lot of oncologists talk about cancer being in remission and not ‘cured’ because it can always come back. I’ve found this a very helpful way to think of how Alem has worked for me, epecially knowing that the damage already done, alongside my increasing age, causes PIRA, and therefore Alem is wonderful, but not some panacea.
Nov 5, 2023·edited Nov 5, 2023Liked by Gavin Giovannoni
Peter Attia, quoting US data says that if you're over 65 and you fall and break something (say femur or hip) - your 12-month mortality, (the probability you will be dead in 12 months after that break) is 15 to 30%.
From age 50 on, we are supposed to shut up, get old and die already. We had a good run. We needn't bother ourselves or our providers with our needs, wants, opinions, suggestions, or questions about our care or what is available our there in terms of meds etc.
This makes me feel so sad, upset and disconsolate. I was given Cladribine a year or so after my diagnosis of PPMS. Then symptomatic treatment. For years I have been asking for AHSCT with no luck. It took a worsening of my MS with new lesion on spinal cord to get Ocrevus. Surely by this stage it’s too late. I will probably cost the NHS more money than AHSCT as my disability increases. Surely health professionals want to improve the health of patients. The tools are there so why not use them? Why not be pro active rather than reactive? I wouldn’t be as disabled as I currently am with my life becoming an existence
I'm hoping to attend the AIMS summit this year. Also due to get a second opinion from Dr Sharrack at Sheffield in a couple of weeks as to whether I'm 'eligible' for HSCT considering current 'inactive' disease and NEIDA on latest scan after starting ofatumamab in January... Glad this is available for me to attend to get more information and speak to others in similar situation.
Hi Giovanni, as far as I understand if you're under the care of an NHS neurologist you should always be entitled to a second opinion from another neuro - you don't need to change neurologist.
I initially saw another neuro privately, who shared the same opinion as my current neuro (that it's best for me to stay on Kesimpta until another relapse, at which point I should reassess), but when I pressed again, my neurologist said he would refer me to Royal Hallamshire in Sheffield (where they had the first large scale randomised trial into AHSCT for RRMS). It's been a long process and I still don't know whether I will be eligible after my apt. with Prof Sharrack, but I think it's worth pressing them to find out...
I'm now just over 3 years since diagnosis and am on my 2nd DMT, though have only officially had one major relapse (when I was diagnosed), but this relapse affected my walking and I'm now a wheelchair user, so I'm keen to stop further progression sooner rather than later.
Hi Melissa. I have PPMS which is seemingly given up on.
Never has IRT been mentioned to me, the first I’ve heard of it was when Prof G brought it up.
I’ve been knocked back every time I have asked for AHSCT. I cant have it they say and the reason being cause I have PPMS. No one has explained to me why that’s a reason! Why yet again my PPMS is a reason.
I know someone with PPMS who managed to get AHSCT on the NHS and is now doing very well. Me on the other hand is getting worse and will probably cost the NHS more money than the cost of HSCT as the disease progresses . The trials exclude me from them because of my age which angers me because I had been asking for HSCT for years.
Not sure if I have the energy or ability to fight anymore
No because of PPMS is a common answer I have found.
I'm sorry to hear this, Giovanni. I've been told I'm not eligible on the NHS either as my disease isn't 'active' enough. I will still be attending the AIMS summit on Saturday to speak to more people and consider my options. All the best to you.
Fly’s in the face of what Prof G advocates ie early intervention!
Just staggering that we have to get worse before treatment is offered!
Money over sensible and humane treatment saving the nhs money in the long term. We all know what MS will do at some point for all of us MSers to varying degrees. Are we not worth a better life?
I have some general Qs, not about AHCST or Cladribine. Alemtuzumab is a drug that has severe thyroid complications and alemtuzumab-induced clinical challenges posed by spontaneous, bidirectional switching between hyperthyroidism and hypothyroidism. Guidelines recommend monitoring thyroid function pre-treatment and every three months for four years following alemtuzumab treatment but others include secondary autoimmune disorders and idiopathic thrombocytopenic purpura, anti-glomerular basement membrane disease, neutropenia, hemolytic anemia and vitilgo among others. I inherited a patient as well, with severe thyroid eye disease following Alemtuzumab use. It is a drug laced with severe side-effects. First do no harm.
Additionally, can someone throw light on the FDA letter (?) to Dr Burt @ NWU and the closure of his lab at NWU ?
When I first me my (current neuro) in mid 2021 he discussed all the options
Told me straight up aHSCT was the best thing for me at my age (35 at the time) and lemtrada as #2
Then he basically said ocrevus and Tysabri are effectively similar. I felt quite informed and if I was JC negative could start Tysabri asap.
The choice was made for me to go into Tysabri due to JC status, Covid still being a huge unknown (this was pre vaccine roll out in australia) and also uncertainty of what Covid would do long term and how effective vaccines would be with b cell depleters
Additionally not being immune compromised due to delta wave was important as antivirals didn’t exist then so with Tysabri it made a lot of sense to start there
We are at a position where ill probable move to an IRT next but if what you are saying my window for efficacy of Mavenclad or lemtrada might have passed now since I started on Tysabri and I’m getting older ?
If Covid wasn’t a thing then I’d probably have gone lemtrada first option
That probably diminishes to a point as I age and on Tysabri longer. For the moment grass is greener as my neuro said in switching away at this point when things are stable
What about for me ppms and on ocrevus? How do I find out?
I can’t believe how difficult it is to know what you should have, what you are eligible for etc etc is this the same for all diseases? As previously said no one has ever mentioned anything about IRT to me
Is the window for efficacy on Lemtrada still looking promising for people who have been on Ocrevus since diagnosis, for 3/4 years and approaching 40? I’m in this category and getting concerned about the growing infection risk on Ocrevus, but looking at the placement of my lesions I am not happy about descalating to a less effective DMD.
Nov 4, 2023·edited Nov 4, 2023Liked by Gavin Giovannoni
I am not qualified to advise. But I did the switch at age 41 when I was PML- and NEDA3. I approached this rationally following this logic:
1) front loading risk to when I am fitter (i.e. now Vs later), 2) the potential of BVL normalisation 3) the potential of a cure 4) the derisking of Tysabri's adverse events relating to immune reconstitution (kicking the can down the road) 5) re-establishing immuno-surveilance once I celebrated my 40th when cancer risks starts increasing materially.
The cost to me was a minimal risk of heart issues (didn't materialise) and about 20% risk of thyroid secondary immunity. Something that can be fixed with a daily pill.
Dear Prof. Giovannoni, I respect your work a lot and I convinced my neuro to put me on cladribine because of it. But as much as would really love the idea that it can offer long-term full remission, the data are not there as they are is with alemtuzumab..
Didn’t work for me. I had it in 2018 but disability has progressed. No one ever told me about the effect of Cladribine on me. It feels that it’s just me with ppms that is left in the dark
Daughter diagnosed in 2019 with RRMS, aged 15.
IRTs were not discussed and we had no knowledge of them although we were convinced the ‘hit it hard early’ was the way to go.
Mum had MS and we were too familiar with the consequences of being under treated.
She started on Dimethyl Fumarate but did move on to Ocralizumab after 12 months.
Our research led us to believe HSCT would bring her the best long term outcome. Her paediatric neurologist was supportive of our opinion but aside from considering other criteria age was a factor.
A few months after turning 18 she was approved for treatment under Dr Kazmi. Unfortunately not NHS funded due to no new lesions on MRI but other factors pointed towards a less favourable long term outlook (heavy lesion load/age at diagnosis/lesion location).
She is now almost 3 months post transplant and doing well.
She’ll be involved in a Q&A session along with 3 others discussing their experience of HSCT at the AIMS Summit at the end of the month.
Being just 19 she is keen to share her perspective on her experience in the hope that others young people in similar situations become aware of their options. (Not named on the programme as only recently been confirmed)
Wonderful! Please thank your daughter for me, Lehmann. - her input will be invaluable xx
What were her thoughts and your thoughts on the risk of infertility?
After careful consideration she took the decision to go through fertility preservation treatment as she considered the risk of infertility too high to leave to chance.
The more I read your newsletter, the more I realize my fear and lack of knowledge has not served me well. I like to think of myself as smart, but MS has pushed me to a level of denial that I am astonished at. Denial and some early trauma related experiences that have contributed to my "toughing" it out on my own, not believing I deserved to receive help etc. I am now looking at Cladribine - 61 years old with increasing progression in the last 4 years, - if this can help me stabilize into the future, I think it is time to advocate for myself and begin a treatment, better later than never. It is so hard for me to contact my neurologist to ask for this potential, which is bananas, but there ya go. A giant, heartfelt thank-you for all you do.
Lastly, how does on measure the MRI metrics of brain volume loss 'reversal' or arrest since we do NOT measure volumetric analyses in 99% of clinics worldwide ???
Thank god in 2015 my daughter aged 17 had the option of lemtrada … 3 months after diagnosis . Normal life since , stable MRI x 8 she now works in NHS , keep fighting the good fight Prof Giovannoni , for the cures and risky treatments , patients need to choice .
As a person who has been treated with Alem, I’m not able to concur with Doc Avasarala. Lots of cancer treatments, among others, are ‘laced with severe side effects’ but are utilised in the care of patients. I can’t say categorically, but understand that the majority of people who seek to end their lives at centres such as those in Switzerland have neurological conditions. Secondly, NHS England data from some 10 years ago, states that the average age of death for PwMS is 66 and that 73% die under the age of 75years. Now in anyone’s book they’ve got to be mighty good reasons to hit MS early and hard, and this doesn’t take account of the challenging job of living with this disease!
I’ve previously joked that ProfG can be vulnerable to being all doom and gloom, as I’ve been so far in this comment, but I do know that I’m currently not depressed or too horribly disabled due to enjoying a good quality of life and having done so for the past six years, thanks to receiving Alem.
I was a month from my 51 birthday when I was diagnosed and the neuro told me I’d likely had MS for years, which reflecting back, I think is probably the case. The subsequent neuro told me that I wasn’t eligible for anything stronger than dimethyl fumarate, exclaiming to me the escalation model (as if this were the only approach to treatment) Thank goodness I’d discovered the Bart’s MS Blog, ProfG vids on YouTube and the guidelines on DMTs by the ABN! After sending a couple of strongly worded emails I was referred to a centre in London and a month before my 52 birthday began my first round of infusions.
The delay caused by this resulted in a second relapse in six months and cost me the use of legs for walking any more than a mile/2 on a good day and I do have some balance issues, quite a lot of pain and some fatigue and cog fog, but, and it feels like a Very Big But, I’ve not deteriorated since the treatment finished in 2017. Now a month from my 60th birthday I’m clearly no spring chicken and I don’t think I was treated early after disease onset, I do however think Alem, for all the associated risk factors, can be ‘life saving’ Treatment with it should be on a person by person basis and any PwMS precluded from receiving it should be based on their health status and not on the risks - these can be managed, primarily through quite rigorous monthly monitoring for four years.
As well as being a strong proponent of flipping the pyramid and use of Alem and ASCT ProfG, as we all know, promotes healthy living too and I wonder if choosing to do this has assisted with my levels of well being since treatment. I would certainly endorse ProfG position on this.
I would always advocate those who are newly diagnosed to learn all about DMTs, their rights as patients, about eligibility criteria and to push for the most effective treatment they can get and that their if their neuro refuses treatment on flimsy or erroneous grounds then ask to be referred to another neuro - preferably one like ProfG who work to flipping the pyramid.
ProfG concerning the ‘cure’ word: I remember reading something you’d written during the past eight years that said ASCT and Alem should be considered in terms of achieving ‘remission’. You explained that a lot of oncologists talk about cancer being in remission and not ‘cured’ because it can always come back. I’ve found this a very helpful way to think of how Alem has worked for me, epecially knowing that the damage already done, alongside my increasing age, causes PIRA, and therefore Alem is wonderful, but not some panacea.
Peter Attia, quoting US data says that if you're over 65 and you fall and break something (say femur or hip) - your 12-month mortality, (the probability you will be dead in 12 months after that break) is 15 to 30%.
It is not all MS!
I forgot to ask what are MSers like me with PPMS meant to do? Just sit back suffer in silence and watch and feel MS tear us apart?
It’s just not fair or humane. Of course if we have money we can go abroad and have AHSCT. Unfortunately I can’t afford it so guess i will suffer
From age 50 on, we are supposed to shut up, get old and die already. We had a good run. We needn't bother ourselves or our providers with our needs, wants, opinions, suggestions, or questions about our care or what is available our there in terms of meds etc.
This makes me feel so sad, upset and disconsolate. I was given Cladribine a year or so after my diagnosis of PPMS. Then symptomatic treatment. For years I have been asking for AHSCT with no luck. It took a worsening of my MS with new lesion on spinal cord to get Ocrevus. Surely by this stage it’s too late. I will probably cost the NHS more money than AHSCT as my disability increases. Surely health professionals want to improve the health of patients. The tools are there so why not use them? Why not be pro active rather than reactive? I wouldn’t be as disabled as I currently am with my life becoming an existence
I'm hoping to attend the AIMS summit this year. Also due to get a second opinion from Dr Sharrack at Sheffield in a couple of weeks as to whether I'm 'eligible' for HSCT considering current 'inactive' disease and NEIDA on latest scan after starting ofatumamab in January... Glad this is available for me to attend to get more information and speak to others in similar situation.
How did you manage to have an appt for a second opinion on AHSCT? Do you have to change Neuros? I cannot find out why I’m not eligible for it!
Hi Giovanni, as far as I understand if you're under the care of an NHS neurologist you should always be entitled to a second opinion from another neuro - you don't need to change neurologist.
I initially saw another neuro privately, who shared the same opinion as my current neuro (that it's best for me to stay on Kesimpta until another relapse, at which point I should reassess), but when I pressed again, my neurologist said he would refer me to Royal Hallamshire in Sheffield (where they had the first large scale randomised trial into AHSCT for RRMS). It's been a long process and I still don't know whether I will be eligible after my apt. with Prof Sharrack, but I think it's worth pressing them to find out...
I'm now just over 3 years since diagnosis and am on my 2nd DMT, though have only officially had one major relapse (when I was diagnosed), but this relapse affected my walking and I'm now a wheelchair user, so I'm keen to stop further progression sooner rather than later.
Hi Melissa. I have PPMS which is seemingly given up on.
Never has IRT been mentioned to me, the first I’ve heard of it was when Prof G brought it up.
I’ve been knocked back every time I have asked for AHSCT. I cant have it they say and the reason being cause I have PPMS. No one has explained to me why that’s a reason! Why yet again my PPMS is a reason.
I know someone with PPMS who managed to get AHSCT on the NHS and is now doing very well. Me on the other hand is getting worse and will probably cost the NHS more money than the cost of HSCT as the disease progresses . The trials exclude me from them because of my age which angers me because I had been asking for HSCT for years.
Not sure if I have the energy or ability to fight anymore
No because of PPMS is a common answer I have found.
I'm sorry to hear this, Giovanni. I've been told I'm not eligible on the NHS either as my disease isn't 'active' enough. I will still be attending the AIMS summit on Saturday to speak to more people and consider my options. All the best to you.
Fly’s in the face of what Prof G advocates ie early intervention!
Just staggering that we have to get worse before treatment is offered!
Money over sensible and humane treatment saving the nhs money in the long term. We all know what MS will do at some point for all of us MSers to varying degrees. Are we not worth a better life?
Thank you, so appreciate all you are doing to advocate high efficiency treatments early!
I have some general Qs, not about AHCST or Cladribine. Alemtuzumab is a drug that has severe thyroid complications and alemtuzumab-induced clinical challenges posed by spontaneous, bidirectional switching between hyperthyroidism and hypothyroidism. Guidelines recommend monitoring thyroid function pre-treatment and every three months for four years following alemtuzumab treatment but others include secondary autoimmune disorders and idiopathic thrombocytopenic purpura, anti-glomerular basement membrane disease, neutropenia, hemolytic anemia and vitilgo among others. I inherited a patient as well, with severe thyroid eye disease following Alemtuzumab use. It is a drug laced with severe side-effects. First do no harm.
Additionally, can someone throw light on the FDA letter (?) to Dr Burt @ NWU and the closure of his lab at NWU ?
Jagannadha Avasarala, MD, PhD
U of KY Medical Center
Every risk needs pondering with weights. What is the likelihood of any of those adverse events happening?
I mean you are an MD right....do you treat with real stuff or just homeopathy?
When I first me my (current neuro) in mid 2021 he discussed all the options
Told me straight up aHSCT was the best thing for me at my age (35 at the time) and lemtrada as #2
Then he basically said ocrevus and Tysabri are effectively similar. I felt quite informed and if I was JC negative could start Tysabri asap.
The choice was made for me to go into Tysabri due to JC status, Covid still being a huge unknown (this was pre vaccine roll out in australia) and also uncertainty of what Covid would do long term and how effective vaccines would be with b cell depleters
Additionally not being immune compromised due to delta wave was important as antivirals didn’t exist then so with Tysabri it made a lot of sense to start there
We are at a position where ill probable move to an IRT next but if what you are saying my window for efficacy of Mavenclad or lemtrada might have passed now since I started on Tysabri and I’m getting older ?
If Covid wasn’t a thing then I’d probably have gone lemtrada first option
Prof G has anecdotal data fresh out of the oven that could comfort you actually.
Link?
I think the window for early treatment varies and it is longer in people on natalizumab.
Happy to consent to any disclosure forms (don't think you need any but I could be wrong) if you are planning to write a case study down the line....
That probably diminishes to a point as I age and on Tysabri longer. For the moment grass is greener as my neuro said in switching away at this point when things are stable
It’s a catch 22 I guess.
What about for me ppms and on ocrevus? How do I find out?
I can’t believe how difficult it is to know what you should have, what you are eligible for etc etc is this the same for all diseases? As previously said no one has ever mentioned anything about IRT to me
Hi,
Is the window for efficacy on Lemtrada still looking promising for people who have been on Ocrevus since diagnosis, for 3/4 years and approaching 40? I’m in this category and getting concerned about the growing infection risk on Ocrevus, but looking at the placement of my lesions I am not happy about descalating to a less effective DMD.
Are you able to elaborate on this? I’m in a similar position as Christian and would consider switching to Alemtuzumab if it seemed prudent.
I am not qualified to advise. But I did the switch at age 41 when I was PML- and NEDA3. I approached this rationally following this logic:
1) front loading risk to when I am fitter (i.e. now Vs later), 2) the potential of BVL normalisation 3) the potential of a cure 4) the derisking of Tysabri's adverse events relating to immune reconstitution (kicking the can down the road) 5) re-establishing immuno-surveilance once I celebrated my 40th when cancer risks starts increasing materially.
The cost to me was a minimal risk of heart issues (didn't materialise) and about 20% risk of thyroid secondary immunity. Something that can be fixed with a daily pill.
Thanks for the feedback. How are you since you’ve gone to Lemtrada. Seems like we are in a similar boat
Are there currently any ongoing CarT trials in SPMS?
The first trial will target early relapsing and more advanced (aka progressive) MS.
How do i register my interest in taking part in this trial? I have PPMS
Dear Prof. Giovannoni, I respect your work a lot and I convinced my neuro to put me on cladribine because of it. But as much as would really love the idea that it can offer long-term full remission, the data are not there as they are is with alemtuzumab..
Yes and no. In the 13+ year follow up of the phase 3 CLARITY cohort over 50% of those treated with cladribine didn't need another DMT.
Didn’t work for me. I had it in 2018 but disability has progressed. No one ever told me about the effect of Cladribine on me. It feels that it’s just me with ppms that is left in the dark
Thank you for your reply. But is that equivalent to having zero disease activity?
Unfortunately we don't know because they were not followed up annually with MRI scans.