The newsletter addresses the differences between maintenance-escalation disease-modifying therapies and immune reconstitution therapies (IRTs) and why it is important to know about this distinction.
If I was at the start of my MS journey I would seriously consider an IRT. However, having had MS for over 25 years and successfully maintained by natalizumab at this stage of life I will stick with my current treatment. However I believe an IRT is a very serious contender for newly diagnosed. Hit it hard and hope it’s a ‘cure’.
My feeling on this is that most patients strive for a cure, to be fixed, or at least the closest thing. This is true of all levels of healthcare. Putting the efficacy of HSCT or Alemtuzumab to one side, there is also the mental satisfaction / reward of 'nipping it in the bud' 'fighting hard' 'moving on'. In contrast, maintenance therapy's serve as a constant reminder that the disease is lurking and you're merely keeping it at bay. That is my own experience (on Ocrevus) and one of the reasons i am seeking out an IRT currently - the others being the higher efficacy, potential for improvements, impact on smouldering MS of course. The difficulty for patients is the point in the disease course at which these decisions need to be made in order to be most effective. I imagine a lot of patients who pursue HSCT are scared into it by a nasty relapse or as a last throw of the dice. Maybe less so with Alemtuzumab as it doesn't have the fatality cloud hanging over it or the hair loss, which seems to be a marker for something being seriously wrong. It is much easier to push these decisions down the road......take the risks if you need to but often then it is too late. Not easy.
My neuro team have suggested that I switch from Ocrevus to Kesimpta. I presume it’s down to ease of administration and one less bed space taken up every six months. I have a question with regard to the pre-meds. As you know methylprednisolone, antihistamines and pain relief are administered prior to each Ocrevus infusion. Why will these not be required with Kesimpta? Is it because the dosage of anti-CD20 is smaller?
I am in full decision to switch: alemtuzumab or ocrelizumab?
I’m a woman and I had my diagnosis of RRMS in 2018 with optic neuritis. Negative rachicentesis and some small lesions, no spinal cord but “only” at the level of the brain. My EDSS was, and still is, equal to 1.
I started with Tecfidera, but after a year and a half my 3 MRIs showed new lesions, some active. So I switch with Fingolimod.
After a year of Fingolimod and 2 still not clean resonances, with 3 new lesions, one of which is active. (My lesions are localized on the left periventricular region, the new active lesion is in the right periventricular area and dull lesions are at the level of the corpus callosum in the right frontal site.)
So here I am now, at 34, with a new therapy change.
My neurologist first proposed Lemtrada to me as the most effective therapy in my case and considering the change from Fingolimod. Then, given my fear of serious side effects and my doubts, she proposed me Ocrelizumab as a safer alternative (she told me that it is also effective but it is true?).
I wouldn’t want to miss the opportunity to make a super effective drug like Lemtrada now that I’m fine, but I don’t know if the risks are actually there.
I am reading your articles to get an idea but it is not easy…
Please, could you give me information that will help me clarify my ideas?
As my MS is classified by you as relapsing Secondary Progressive MS, Please can you seriously consider whether I am having a relapse at the moment & if I can be prescribed a course of methylprednisolone tablets 500mg daily for 5 days - please.
I have had MS for almost 17 years & have only ever felt THIS bad, with such severe mobility issues, exhaustion & eyesight problems when I have had a relapse.
“ Overview. An exacerbation of MS (also known as a relapse, attack or flare-up) is the occurence new symptoms or the worsening of old symptoms. It can be very mild, or severe enough to interfere with a person's ability to function.”
I definitely feel that this is a severe exacerbation (involving vision issues; severe weakness & poor balance) which is interfering with my mobility, safety or overall ability to function,
Hi Prof G., thank you for a great post. Without a doubt, I would choose IRT in a heart beat. The accumulation of severe disability, loss of qualify of life with a grisly prognosis was in clear sight at diagnosis in 2014. Unfortunately, at that time I did not know HSCT was an option and went immediately for Alemtuzumab instead. That choice was a waste of valuable years waiting to see if it was effective for my very aggressive/rare MS. On my third round of Alemtuzumab I had a severe adverse reaction - it proliferated my lymphocytes instead of depletion - and jettisoned me into a major relapse, setting me further back. If I had done HSCT at the outset I could have used those years instead for a real chance of avoiding losing everything. I would risk my life to get rid of this disease and get a decent quality of life back.
I was treated by yourself and professor Miller, 21 years ago at Queen's Square with Mitoxantrone.Yes it saved my life, but if I knew then what I know now having lived with MS for 21 years and suffering the many complications of it, I would don't have had it and would not recommend it to anyone. Angela
I would love to get Mavenclad.. but in my Country I need to be worse (like more than 4 in EDSS)... I'm 0.5 at the moment..
I have 3 heart conditions besides MS and a Pacemaker.. I didn't tolerate interferon (and I developed the conditions while on it), So, they are thinking what to give me but because I'm "ok" they don't worry to much..
I would prefer to be inmunosupressed for a while (2 years of mavenclad) and then deal with my heart the rest of the time instead of that trial and error that never stops.. I tend to react bad to drugs..
But.. again.. I need to be worse to get Mavenclad.. (only 1 attack, 2 lessions and drop foot for now)
I am in the Republic of Ireland and have a diagnosis of HARRMS since 2014. I have had glatiramer acetate, dimethyl fumarate, natalizumab, alemtuzumab and am currently on ocrelizumab. All of these medications have given sub optimal responses aside from alemtuzumab, and my neurologist is presenting my case today for HSCT in the UK. I am conflicted about HSCT but feel it is my only real tangible option. There is a part of me that wonders if I should have a third round of alemtuzumab instead, as better the devil you know and all that. If you were in my shoes would you think HSCT is a better option?
Another invaluable post. Thank you. I never was offered any treatment, maybe because of my age at diagnosis. I'm not sure any would be available to me now, but for newly diagnosed pwMS this is such a useful explanation.
I watched a video by Caroline Wyatt. It was very moving to hear her explanation of the disease course of her MS and rather sad that , having spent money for AHSCT in Mexico a few of years back, she feels she's deteriorated markedly notwithstanding. As a BBC correspondent her testimony was very clear. Why the deterioration? Was it because it was early days? Did she choose badly?
Two more questions. What side effects are reported after the depletion phase and before the reconstitution phase? And, is the patient given any, or a suite of vaccinations against the sorts of diseases that they might be prey to after the depletion phase?
This is so interesting but once again leaves me quite depressed as the post code lottery means that many of us are not offered any choice. At the start of august after an MRI showing a relapse treatment for the first time ever, siponimod. I was sent documents to read but at no time have been able to actually speak to the MS nurse or the neurologist about it. I decided to accept the treatment. Two months later I’m still waiting to have tests.
Lemtrada as first line and NEDA since 2015/16 - my amazing MS nurse gave me the courage to take it as it had just been approved by NICE. I’ve not regretted it and I hope all the information you produce here will remove any hesitancy for newly diagnosed pwMS, it’s a no-brainer!
I’m interested in the reconstituted immune system never being the same - do you mean without the errant auto immune elements or are there other changes that are permanent? Also curious about the live vaccines, can pwMS ever have live vaccines, I thought not? Thank you!
Thanks for this, it's a useful explainer of the differences between treatment approaches. The challenge in the UK is many of the treatments are not available as a 1st line. I'm persuaded that high-efficacy or IRT offer the best chance of long-term remission, but options are limited. On balance I would probably opt for Cladribine if it were available. Given the Covid situation there's hesitancy around prescribing Ocrevus at the moment, which means my options are limited to the interferons.
Hi Prof G, your site is a fantastic resource. Thank you.
In your table ‘NEDA unreliable metric to assess efficacy’ after IRT, is that because activity indicates the need for repeat courses? What is the alternative to monitor efficacy after IRT? Surely it’s clinical relapses, MRI, OCB, etc, etc, etc as for maintenance treatments?
I was diagnosed in 2017 RRMS. I was initially recommended tecfidera, but I had several significant relapses in the year I took it, plus the side effects were terrible.
I decided I wanted alemtuzumab as my next option and was granted. I completed round 2 in Nov 2019. The scans I've had remained stable since 2018, but I'm sure I have smoldering MS. I feel I'm declining. I've been waiting 3 months for a contrast MRI. I would definitely be interested in additional treatments available after alemtuzumab.
If I was at the start of my MS journey I would seriously consider an IRT. However, having had MS for over 25 years and successfully maintained by natalizumab at this stage of life I will stick with my current treatment. However I believe an IRT is a very serious contender for newly diagnosed. Hit it hard and hope it’s a ‘cure’.
My feeling on this is that most patients strive for a cure, to be fixed, or at least the closest thing. This is true of all levels of healthcare. Putting the efficacy of HSCT or Alemtuzumab to one side, there is also the mental satisfaction / reward of 'nipping it in the bud' 'fighting hard' 'moving on'. In contrast, maintenance therapy's serve as a constant reminder that the disease is lurking and you're merely keeping it at bay. That is my own experience (on Ocrevus) and one of the reasons i am seeking out an IRT currently - the others being the higher efficacy, potential for improvements, impact on smouldering MS of course. The difficulty for patients is the point in the disease course at which these decisions need to be made in order to be most effective. I imagine a lot of patients who pursue HSCT are scared into it by a nasty relapse or as a last throw of the dice. Maybe less so with Alemtuzumab as it doesn't have the fatality cloud hanging over it or the hair loss, which seems to be a marker for something being seriously wrong. It is much easier to push these decisions down the road......take the risks if you need to but often then it is too late. Not easy.
My neuro team have suggested that I switch from Ocrevus to Kesimpta. I presume it’s down to ease of administration and one less bed space taken up every six months. I have a question with regard to the pre-meds. As you know methylprednisolone, antihistamines and pain relief are administered prior to each Ocrevus infusion. Why will these not be required with Kesimpta? Is it because the dosage of anti-CD20 is smaller?
I am in full decision to switch: alemtuzumab or ocrelizumab?
I’m a woman and I had my diagnosis of RRMS in 2018 with optic neuritis. Negative rachicentesis and some small lesions, no spinal cord but “only” at the level of the brain. My EDSS was, and still is, equal to 1.
I started with Tecfidera, but after a year and a half my 3 MRIs showed new lesions, some active. So I switch with Fingolimod.
After a year of Fingolimod and 2 still not clean resonances, with 3 new lesions, one of which is active. (My lesions are localized on the left periventricular region, the new active lesion is in the right periventricular area and dull lesions are at the level of the corpus callosum in the right frontal site.)
So here I am now, at 34, with a new therapy change.
My neurologist first proposed Lemtrada to me as the most effective therapy in my case and considering the change from Fingolimod. Then, given my fear of serious side effects and my doubts, she proposed me Ocrelizumab as a safer alternative (she told me that it is also effective but it is true?).
I wouldn’t want to miss the opportunity to make a super effective drug like Lemtrada now that I’m fine, but I don’t know if the risks are actually there.
I am reading your articles to get an idea but it is not easy…
Please, could you give me information that will help me clarify my ideas?
As my MS is classified by you as relapsing Secondary Progressive MS, Please can you seriously consider whether I am having a relapse at the moment & if I can be prescribed a course of methylprednisolone tablets 500mg daily for 5 days - please.
I have had MS for almost 17 years & have only ever felt THIS bad, with such severe mobility issues, exhaustion & eyesight problems when I have had a relapse.
https://mstrust.org.uk/a-z/steroids-methylprednisolone
“ Overview. An exacerbation of MS (also known as a relapse, attack or flare-up) is the occurence new symptoms or the worsening of old symptoms. It can be very mild, or severe enough to interfere with a person's ability to function.”
I definitely feel that this is a severe exacerbation (involving vision issues; severe weakness & poor balance) which is interfering with my mobility, safety or overall ability to function,
Hi Prof G., thank you for a great post. Without a doubt, I would choose IRT in a heart beat. The accumulation of severe disability, loss of qualify of life with a grisly prognosis was in clear sight at diagnosis in 2014. Unfortunately, at that time I did not know HSCT was an option and went immediately for Alemtuzumab instead. That choice was a waste of valuable years waiting to see if it was effective for my very aggressive/rare MS. On my third round of Alemtuzumab I had a severe adverse reaction - it proliferated my lymphocytes instead of depletion - and jettisoned me into a major relapse, setting me further back. If I had done HSCT at the outset I could have used those years instead for a real chance of avoiding losing everything. I would risk my life to get rid of this disease and get a decent quality of life back.
I was treated by yourself and professor Miller, 21 years ago at Queen's Square with Mitoxantrone.Yes it saved my life, but if I knew then what I know now having lived with MS for 21 years and suffering the many complications of it, I would don't have had it and would not recommend it to anyone. Angela
So helpful thank you. I wish IRT was discussed and offered at outset esp if poor prognostic indicators.
I would love to get Mavenclad.. but in my Country I need to be worse (like more than 4 in EDSS)... I'm 0.5 at the moment..
I have 3 heart conditions besides MS and a Pacemaker.. I didn't tolerate interferon (and I developed the conditions while on it), So, they are thinking what to give me but because I'm "ok" they don't worry to much..
I would prefer to be inmunosupressed for a while (2 years of mavenclad) and then deal with my heart the rest of the time instead of that trial and error that never stops.. I tend to react bad to drugs..
But.. again.. I need to be worse to get Mavenclad.. (only 1 attack, 2 lessions and drop foot for now)
Hi Prof G,
I am in the Republic of Ireland and have a diagnosis of HARRMS since 2014. I have had glatiramer acetate, dimethyl fumarate, natalizumab, alemtuzumab and am currently on ocrelizumab. All of these medications have given sub optimal responses aside from alemtuzumab, and my neurologist is presenting my case today for HSCT in the UK. I am conflicted about HSCT but feel it is my only real tangible option. There is a part of me that wonders if I should have a third round of alemtuzumab instead, as better the devil you know and all that. If you were in my shoes would you think HSCT is a better option?
Another invaluable post. Thank you. I never was offered any treatment, maybe because of my age at diagnosis. I'm not sure any would be available to me now, but for newly diagnosed pwMS this is such a useful explanation.
I watched a video by Caroline Wyatt. It was very moving to hear her explanation of the disease course of her MS and rather sad that , having spent money for AHSCT in Mexico a few of years back, she feels she's deteriorated markedly notwithstanding. As a BBC correspondent her testimony was very clear. Why the deterioration? Was it because it was early days? Did she choose badly?
Two more questions. What side effects are reported after the depletion phase and before the reconstitution phase? And, is the patient given any, or a suite of vaccinations against the sorts of diseases that they might be prey to after the depletion phase?
This is so interesting but once again leaves me quite depressed as the post code lottery means that many of us are not offered any choice. At the start of august after an MRI showing a relapse treatment for the first time ever, siponimod. I was sent documents to read but at no time have been able to actually speak to the MS nurse or the neurologist about it. I decided to accept the treatment. Two months later I’m still waiting to have tests.
Lemtrada as first line and NEDA since 2015/16 - my amazing MS nurse gave me the courage to take it as it had just been approved by NICE. I’ve not regretted it and I hope all the information you produce here will remove any hesitancy for newly diagnosed pwMS, it’s a no-brainer!
I’m interested in the reconstituted immune system never being the same - do you mean without the errant auto immune elements or are there other changes that are permanent? Also curious about the live vaccines, can pwMS ever have live vaccines, I thought not? Thank you!
Thanks for this, it's a useful explainer of the differences between treatment approaches. The challenge in the UK is many of the treatments are not available as a 1st line. I'm persuaded that high-efficacy or IRT offer the best chance of long-term remission, but options are limited. On balance I would probably opt for Cladribine if it were available. Given the Covid situation there's hesitancy around prescribing Ocrevus at the moment, which means my options are limited to the interferons.
Hi Prof G, your site is a fantastic resource. Thank you.
In your table ‘NEDA unreliable metric to assess efficacy’ after IRT, is that because activity indicates the need for repeat courses? What is the alternative to monitor efficacy after IRT? Surely it’s clinical relapses, MRI, OCB, etc, etc, etc as for maintenance treatments?
I was diagnosed in 2017 RRMS. I was initially recommended tecfidera, but I had several significant relapses in the year I took it, plus the side effects were terrible.
I decided I wanted alemtuzumab as my next option and was granted. I completed round 2 in Nov 2019. The scans I've had remained stable since 2018, but I'm sure I have smoldering MS. I feel I'm declining. I've been waiting 3 months for a contrast MRI. I would definitely be interested in additional treatments available after alemtuzumab.