The WHO's decision to add three MS DMTs to their essential medicines list, including rituximab, finally vindicates my off-label prescribing list. But cladribine will be the real game-changer.
'Fantastic' and 'Amazing' and congratulations etc, are to some extent entirely justified? All this has happened in therapeutic darkness and without a clear knowledge of the pathogenetic mechanisms occurring in the MS CNS. This has been to the happy advantage of Pharma and it continues in some darkness. It will continue until the fundamental questions are solved by focussed laboratory research. The technical resources are available to achieve this but the pharma promoted expenditure will eclipse the very much less expensive research into fundamental mechanisms. For example. If it is postulated that EBV is essential, what is the mechanism? If there is a specific autoimmune target, discover what it is. If there is a vital susceptibility gene please identify. If there is a key environmental signal, what is it? I have a serious worry that Pharma will not particularly appreciate these particular answers.
Fantastic!!! Hopefully more help for more people. Options for treatment is so important. We need more champions like you to understand this insidious disease
Wonderful! Thank you for your continued advocacy and all you've done for PWMS. I appreciate you and all the information you provide for us here. For all the bitching and moaning I do about how slow advancements are in MS and about the inequality of resources (including educated MS neuros) I would be remiss not to mention how grateful I am to live in Canada and how I've been able to not only access medication, but also doctors. Even though I am progressing and my brain continues to collect lesions and experience accelerated shrinkage and atrophy, I am somehow still able to write long winded sentences lol Wising everyone a gentle week.
Very interesting. I was dx in '94 at the same time as the interferons had just been licensed. I saw Prof. MacDonald at Queen Sq to confirm my dx. He advised against using beta interferons, which backs up what you are saying about 'conservative' MS management. I had to ask for Tysabri in 2009, my first DMT.
J, my diagnosis was here in the states in 1995. At some point, there was a lottery for Betaseron. I passed on it. But when my then RRMS worsened after a complete remission for several years following very high dose chemotherapy with one of the drugs being cyclophosphamide, I was prescribed interferon beta 1-a (Avonex). I don’t know your age at diagnosis, but I regret not opting for Tysabri when it became available. I wish you well.🌷
This is amazing, so grateful to think that treatment options will be fairer now and we can bridge inequalities in some way. Again as always really appreciate your help with this work Dr Giovannoni
When you first came to this country, I had paediatric MS. Then treatments were invented. And the entire time, I was severely disabled, and denied access to even a diagnosis by the NHS. My MS ran its natural course with no treatment for decades.
Anyone with MS who gets as far as a diagnosis is already one of the lucky ones. I could not access a neurologist or MRI scan in Yorkshire. Globally, there must be many people in that position.
DMTs are utterly useless to anyone who can't even access an MRI. The first step has to be giving people access to diagnosis. And that very much includes the UK. Especially for those in the lowest socioeconomic classes.
This is great news about WHO's decision to add three MS DMTs to their essential medicines list.
I've followed what's happening with MS since my own RRMS diagnosis in 2014, it's interesting to hear your thoughts on the development of MS treatments in recent years.
It's not a fast moving place at all even in the 9 years since my own MS diagnosis but I'm grateful that there are signs of progress with WHO now, long may it continue. Well done to those in the MS space for this achievement. It is appreciated.
That’s such a brilliant achievement, and thank you again ProfG. Great news about Cladribine, what about Kesimpta - it is so easy to administer and an effective DMT for MS? I have no idea the actual cost of Kesimpta because we have PBS in Australia and it cost around $50 per month here
Ofatumumab (Kesimpta) is still patiented and very high cost, which is why it was not considered. GA, cladribine and rituximab are all off patent and hence relatively cheap. Oral cladribine will come off patent in 2028, unless Merck get an extension based on its formulation. However, you can use the IV or SC formulations. At Barts-MS we have been using the latter formulations for a few years now.
ProfG, given that Cladribine is a IRT and Kesimpta is a highly effective DMT, I don’t understand why my daughter (22yo at onset) was given a course of Cladribine for a year & was doing well, but after a change in neurologist) was given Kesimpta
She’s now 25yo, 2years on Kesimpta - but from what I’ve read of your writings, she’s better of on Kesimpta in terms of a possibility of a “cure” or long term remission without a constant wipe out of her immune systems w Kesimpta
I can’t imagine she will be forever on Kesimpta, every month… could she potentially switch back to Cladribine?
Dr. G. From reading your information, I get the false sense that MS DMT’s are able to cure MS or at least lessen it’s effects, this is not necessarily true. Why are readers lured into believing that this is possible? Yes, there are treatments available for MS now, which were not available in the past, but they are not as effective as you would like us to believe! I tend to agree with Frederick’s views!!!
No. The only DMTs that could cure MS are IRTs, i.e. they put you into long-term remission off therapy. It is being off therapy that is an important component of the definition. I have never suggested other DMTs can cure MS.
Thank you very much for your response! I realized after I sent my message, that I’d accidentally written ‘cure’, sorry about that. It was my wishful thinking, erupting into my forebrain!!!
Nothing that I am aware of. When it comes to disease such as MS they are reactive rather than proactive. Unless the MS community approaches the WHO with a submission about AHSCT they are unlikely to do anything. Please be aware that AHSCT is a procedure and not a medicine hence it will not be included in the EML.
Sorry to be a party pooper in face of some. great news but you make but a single reference to PPMS and that only en passant. As a result you overwhelmingly gave the false impression that DMTS are available across the MS space. As you know better than me, as a 70 year with PPMS the cupboard is completely bare. Please be more attentive to our plight. Or is there good news I don’t know about?
Not sure if you are aware that I don't consider PPMS to be a different disease. PPMS is MS and the only difference is that pwPPMS present later, because they don't have a sentinel event or an obvious attack. PwPPMS sadly present with clinically apparent worsening or SAW (smoldering-associated worsening) because they have lost reserve in the pathway concerned. I have little doubt that PPMS will respond to the same treatments as relapse-onset disease. Ocrelizumab and rituximab teach us this and it is important to treat PPMS to prevent further damage.
Yes I’m fully aware that you believe they are but one disease and who am I to argue, however and fortunately far from all neurologists share your view and age comes into the reckoning. Last year I asked my French neurologist about Ocrevus and he said I’m aged barred. Do you have any suggestions as to what I can do?
We don't have an age limit in the UK. This would be challenged in the courts under ageism legislation. You could ask for off-label cladribine? This is what we offer patients who are not eligible for licensed therapies under the NHS England algorithm.
Prof G, like Nigel, at age 70, does this mean I should ask my neurologist for cladribine? My blood counts, other than on the low side of WBCs/RBCs are fine. I am not happy with this progression.
Nigel, I am SPMS, now, NEID/SAW. My neurologist wanted to prescribe siponomod. Prof G pointed out the trials cut off at 50 yr/old, and I have some legacy blood count issues. We are in the same boat.🌷
Yes, I saw that. Perhaps that could give us us a number of good years. Not sure they’ll ok it here in the states on my, ahem, plan, but I’m ready to ask!
Congratulations, great news. I'm saddened to hear of the issues PWMS face in resource-poor countries. What can be done to help them? Additionally, I'm always surprised that Cladribine isn't more popular: I took it in 2019/20, choosing it because of how low maintenance it was, and so far, so good in terms of disease progression.
'Fantastic' and 'Amazing' and congratulations etc, are to some extent entirely justified? All this has happened in therapeutic darkness and without a clear knowledge of the pathogenetic mechanisms occurring in the MS CNS. This has been to the happy advantage of Pharma and it continues in some darkness. It will continue until the fundamental questions are solved by focussed laboratory research. The technical resources are available to achieve this but the pharma promoted expenditure will eclipse the very much less expensive research into fundamental mechanisms. For example. If it is postulated that EBV is essential, what is the mechanism? If there is a specific autoimmune target, discover what it is. If there is a vital susceptibility gene please identify. If there is a key environmental signal, what is it? I have a serious worry that Pharma will not particularly appreciate these particular answers.
Fantastic!!! Hopefully more help for more people. Options for treatment is so important. We need more champions like you to understand this insidious disease
Absolutely amazing news and thank you (on behalf of pwMS worldwide) for taking that 6 month sabbatical and all your work on the off-label DMT list.
Email: Hi doctor, good news today. Just would like to know if there will be anything for SPMS? I’m forever hopeful.
My answer to this question is the same as the one to PPMS. SPMS is MS and is still modifiable.
Wonderful! Thank you for your continued advocacy and all you've done for PWMS. I appreciate you and all the information you provide for us here. For all the bitching and moaning I do about how slow advancements are in MS and about the inequality of resources (including educated MS neuros) I would be remiss not to mention how grateful I am to live in Canada and how I've been able to not only access medication, but also doctors. Even though I am progressing and my brain continues to collect lesions and experience accelerated shrinkage and atrophy, I am somehow still able to write long winded sentences lol Wising everyone a gentle week.
Hi Me! I personally appreciate your bitching and moaning. Do some for me too..It’s challenging our brains! Cheers! 🌷
Lol. Next time I bitch and moan, I will do it for you too in spirit! Thanks for always having my back haha!
Very interesting. I was dx in '94 at the same time as the interferons had just been licensed. I saw Prof. MacDonald at Queen Sq to confirm my dx. He advised against using beta interferons, which backs up what you are saying about 'conservative' MS management. I had to ask for Tysabri in 2009, my first DMT.
J, my diagnosis was here in the states in 1995. At some point, there was a lottery for Betaseron. I passed on it. But when my then RRMS worsened after a complete remission for several years following very high dose chemotherapy with one of the drugs being cyclophosphamide, I was prescribed interferon beta 1-a (Avonex). I don’t know your age at diagnosis, but I regret not opting for Tysabri when it became available. I wish you well.🌷
This is amazing, so grateful to think that treatment options will be fairer now and we can bridge inequalities in some way. Again as always really appreciate your help with this work Dr Giovannoni
When you first came to this country, I had paediatric MS. Then treatments were invented. And the entire time, I was severely disabled, and denied access to even a diagnosis by the NHS. My MS ran its natural course with no treatment for decades.
Anyone with MS who gets as far as a diagnosis is already one of the lucky ones. I could not access a neurologist or MRI scan in Yorkshire. Globally, there must be many people in that position.
DMTs are utterly useless to anyone who can't even access an MRI. The first step has to be giving people access to diagnosis. And that very much includes the UK. Especially for those in the lowest socioeconomic classes.
I’m so sorry for what you have gone through.🌷
Thank you, it is a lot to live with. I appreciate you always being so kind. 🥀
This is great news about WHO's decision to add three MS DMTs to their essential medicines list.
I've followed what's happening with MS since my own RRMS diagnosis in 2014, it's interesting to hear your thoughts on the development of MS treatments in recent years.
It's not a fast moving place at all even in the 9 years since my own MS diagnosis but I'm grateful that there are signs of progress with WHO now, long may it continue. Well done to those in the MS space for this achievement. It is appreciated.
Karen
That’s such a brilliant achievement, and thank you again ProfG. Great news about Cladribine, what about Kesimpta - it is so easy to administer and an effective DMT for MS? I have no idea the actual cost of Kesimpta because we have PBS in Australia and it cost around $50 per month here
Ofatumumab (Kesimpta) is still patiented and very high cost, which is why it was not considered. GA, cladribine and rituximab are all off patent and hence relatively cheap. Oral cladribine will come off patent in 2028, unless Merck get an extension based on its formulation. However, you can use the IV or SC formulations. At Barts-MS we have been using the latter formulations for a few years now.
ProfG, given that Cladribine is a IRT and Kesimpta is a highly effective DMT, I don’t understand why my daughter (22yo at onset) was given a course of Cladribine for a year & was doing well, but after a change in neurologist) was given Kesimpta
She’s now 25yo, 2years on Kesimpta - but from what I’ve read of your writings, she’s better of on Kesimpta in terms of a possibility of a “cure” or long term remission without a constant wipe out of her immune systems w Kesimpta
I can’t imagine she will be forever on Kesimpta, every month… could she potentially switch back to Cladribine?
Thanking you 🙏
https://gavingiovannoni.substack.com/p/case-study-switching-from-ocrelizumab-e79
Dr. G. From reading your information, I get the false sense that MS DMT’s are able to cure MS or at least lessen it’s effects, this is not necessarily true. Why are readers lured into believing that this is possible? Yes, there are treatments available for MS now, which were not available in the past, but they are not as effective as you would like us to believe! I tend to agree with Frederick’s views!!!
No. The only DMTs that could cure MS are IRTs, i.e. they put you into long-term remission off therapy. It is being off therapy that is an important component of the definition. I have never suggested other DMTs can cure MS.
Thank you very much for your response! I realized after I sent my message, that I’d accidentally written ‘cure’, sorry about that. It was my wishful thinking, erupting into my forebrain!!!
again this is great news, and u r absolutely brilliant as person of science and as a human of kindness.
sorry to ask:
what does the WHO have to say about aHSCT for MS?
Nothing that I am aware of. When it comes to disease such as MS they are reactive rather than proactive. Unless the MS community approaches the WHO with a submission about AHSCT they are unlikely to do anything. Please be aware that AHSCT is a procedure and not a medicine hence it will not be included in the EML.
Sorry to be a party pooper in face of some. great news but you make but a single reference to PPMS and that only en passant. As a result you overwhelmingly gave the false impression that DMTS are available across the MS space. As you know better than me, as a 70 year with PPMS the cupboard is completely bare. Please be more attentive to our plight. Or is there good news I don’t know about?
Not sure if you are aware that I don't consider PPMS to be a different disease. PPMS is MS and the only difference is that pwPPMS present later, because they don't have a sentinel event or an obvious attack. PwPPMS sadly present with clinically apparent worsening or SAW (smoldering-associated worsening) because they have lost reserve in the pathway concerned. I have little doubt that PPMS will respond to the same treatments as relapse-onset disease. Ocrelizumab and rituximab teach us this and it is important to treat PPMS to prevent further damage.
Yes I’m fully aware that you believe they are but one disease and who am I to argue, however and fortunately far from all neurologists share your view and age comes into the reckoning. Last year I asked my French neurologist about Ocrevus and he said I’m aged barred. Do you have any suggestions as to what I can do?
We don't have an age limit in the UK. This would be challenged in the courts under ageism legislation. You could ask for off-label cladribine? This is what we offer patients who are not eligible for licensed therapies under the NHS England algorithm.
Prof G, like Nigel, at age 70, does this mean I should ask my neurologist for cladribine? My blood counts, other than on the low side of WBCs/RBCs are fine. I am not happy with this progression.
:(
Nigel, I am SPMS, now, NEID/SAW. My neurologist wanted to prescribe siponomod. Prof G pointed out the trials cut off at 50 yr/old, and I have some legacy blood count issues. We are in the same boat.🌷
Hi, Did you see that Prof G. said I should try.for Cladribrine?
Yes, I saw that. Perhaps that could give us us a number of good years. Not sure they’ll ok it here in the states on my, ahem, plan, but I’m ready to ask!
Positive podcast is appreciated Thankyou
Congratulations, great news. I'm saddened to hear of the issues PWMS face in resource-poor countries. What can be done to help them? Additionally, I'm always surprised that Cladribine isn't more popular: I took it in 2019/20, choosing it because of how low maintenance it was, and so far, so good in terms of disease progression.
Thanks very much, I'll Eton to that.