Yes, we need to go beyond the B-cell. We can’t accept the status quo and think we have sorted MS out because most pwMS treated early with MS are NEIDA.
I agree that just using NEIDA as an endpoint for effectiveness of DMT treatment is just scratching the surface. I am in the SAW category, but fortunately it's been very slow progression. I like your theory of EBV being the essential necessity for developing MS. That is a major shift for opening up a whole class of new treatments. The medical profession will resist as they did in resisting the discovery of helicobacter causing ulcers rather than stress. All us MSers want the progressing disability to STOP. Please make it stop!
I now understand what bothered me about the approach I saw in the French neurology professors I read on social networks or heard via webinar. No one has ever talked about trying to understand the origins of MS and the progression, let alone changing the paradigm of even RR treatment. It's sad. One does not expect such reflections from frontline neurologists - they apply the protocol. But I would have expected more reflections from the professors. Perhaps they reserve their reflections for discussion among the experts. However, the sentence pronounced by a professor to summarise a symposium on MS treatments held in France recently - we are beginning to have ideas concerning progressive MS - saddens me because the disease has existed for centuries and we are just beginning to have ideas!!!. Ok. They are doing their job well: they test pharmaceutical companies' products and try to manage MS the symptoms, but I ask myself why there are not more committed professors like Prog Giavanonni to make things move forward ?
When would you think about switching to alemtuzumab in this situation? I find that my team is not really offering this after I had to switch off tysabri for JC virus titer spike and am very attracted to this therapeutic option!
As a person with ms on anti cd20 I agree. It has been an amazing evolution but is by no means a cure and we cannot get complacent. And choosing between life in a mask always being on the outside or repeated covid infections always feeling sick is no way to live. You have to give up normal life while watching others live and feeling like life is passing you by.
Time is brain, as you say. Thank you for fighting the good fight.
'We can’t accept the status quo and think we have sorted MS out because most pwMS treated early with MS are NEIDA.'
The gigantic problem is that some people with MS aren't treated early. The NHS denied me access to an MS disgnosis for decades, since I was a child; I was severely disabled the entire time. One can call it gaslighting or gross medical negligence.
I have 'significant cerebral atrophy'. I've just had Alemtuzumab; it might stop me getting worse, but hasn't made me better. Is it considered too late for someone like me, and too hard to try undo damage already done? Is research being done to help people who had untreated MS for many, many years? 🤕
There will probably always be people like me, outliers, who have been denied healthcare. Because of where we are in the world (Yorkshire in my case...), our socioeconomic status, and abuse by family and doctors. What of us?
I like the term SAW and that it rhymes with RAW is a bonus. At the end of the day it's the same as old-fashioned 'progression' which always seems ironic as progression is usually taken to be a positive!
I was thinking about this newsletter in the middle of the night (probably because this time next week I'll be having dose #5). It's made me feel a bit low, TBH - but I guess this is the risk we take when we try to read as much as possible about our condition: it can occasionally dent the optimism that feels integral to living well with MS.
Anyway, I'll try to shake off the blues and look at this pragmatically: do other patients understand my hypothetical reluctance to de-risk to a less effective therapy (e.g. teriflunomide), because then I might not be able to access highly effective therapies in future? When it's being drummed into our heads to hit MS hard, it feels like a strange decision to actively make. Similarly, it's also crossed my mind: in future, would I be less likely to be able to access BTKis if I de-risked?
(On another note: it's the cancer risk that makes me feel apprehensive about L/T ocrelizumab use. Am I naive to presume that there's some central database which is keeping tabs on this data....?!)
May 9, 2023·edited May 9, 2023Liked by Gavin Giovannoni
Prof G,
I have convinced my centre to switch me from Ocrevus to Lemtrada following your articles.
Do you think alemtuzumab has, in a young person, early in their diagnosis, the potential to stop smouldering MS and BVL?
Or, do you think it is merely the best available option that simply *may* impact smouldering MS (I.e. would it be better to hold out on Ocrevus and wait for BTKis?)?
Great stuff. You had enthusiastically highlighted NfL testing very recently…can you share some thoughts regarding the degree of importance would you assign to sNfL testing results following a decision to de-risk an individual? As important as MRI, perhaps? Annually? Finally…any enthusiasm regarding plasma GFAP testing in addition?
I like SAW, because that’s exactly where I am. NEID and extremely frustrated not to mention getting worse. NEID does not mean “cured” now go away, end of, although that’s the standard of treatment, if you want to call it that. We can have huge flares with NEID and nothing to turn to. It’s a terrible situation for those who have been fortunate enough to achieve first rate responses to good DMTs only to lose what you’ve gained or progress you’ve made. You’re “cured” because the goal is NEID? No you’ll be SAW!!
“I am predicting relative to teriflunomide as a class, BTKIs will reduce disability progression by about 45% (range 40-60%).” Doesn’t sound that impressive to me! Would you be happy knowing that your brain / spinal cord was still being shredded (albeit slightly slower) despite being on anti-CD20 and BTKi therapies? What’s needed to ‘stop’ disability progression ie 100%? Will anti-virals make a greater impact on reducing disability progression?
I agree with you prof G. Lesions are not the heart of MS. Maybe the real MS is the "thing" that drives progression in PPMS or non active SPMS patients (who have or dont have lesions but still their MS is progressing). I really would like BTK be very effective in PPMS. There are limited options for patients with this form :-( Do you think that BTK can be effective in PPMS? Or not because in this form people have antibodies in CSF which can drive their MS?
I agree that just using NEIDA as an endpoint for effectiveness of DMT treatment is just scratching the surface. I am in the SAW category, but fortunately it's been very slow progression. I like your theory of EBV being the essential necessity for developing MS. That is a major shift for opening up a whole class of new treatments. The medical profession will resist as they did in resisting the discovery of helicobacter causing ulcers rather than stress. All us MSers want the progressing disability to STOP. Please make it stop!
I now understand what bothered me about the approach I saw in the French neurology professors I read on social networks or heard via webinar. No one has ever talked about trying to understand the origins of MS and the progression, let alone changing the paradigm of even RR treatment. It's sad. One does not expect such reflections from frontline neurologists - they apply the protocol. But I would have expected more reflections from the professors. Perhaps they reserve their reflections for discussion among the experts. However, the sentence pronounced by a professor to summarise a symposium on MS treatments held in France recently - we are beginning to have ideas concerning progressive MS - saddens me because the disease has existed for centuries and we are just beginning to have ideas!!!. Ok. They are doing their job well: they test pharmaceutical companies' products and try to manage MS the symptoms, but I ask myself why there are not more committed professors like Prog Giavanonni to make things move forward ?
When would you think about switching to alemtuzumab in this situation? I find that my team is not really offering this after I had to switch off tysabri for JC virus titer spike and am very attracted to this therapeutic option!
As a person with ms on anti cd20 I agree. It has been an amazing evolution but is by no means a cure and we cannot get complacent. And choosing between life in a mask always being on the outside or repeated covid infections always feeling sick is no way to live. You have to give up normal life while watching others live and feeling like life is passing you by.
Time is brain, as you say. Thank you for fighting the good fight.
'We can’t accept the status quo and think we have sorted MS out because most pwMS treated early with MS are NEIDA.'
The gigantic problem is that some people with MS aren't treated early. The NHS denied me access to an MS disgnosis for decades, since I was a child; I was severely disabled the entire time. One can call it gaslighting or gross medical negligence.
I have 'significant cerebral atrophy'. I've just had Alemtuzumab; it might stop me getting worse, but hasn't made me better. Is it considered too late for someone like me, and too hard to try undo damage already done? Is research being done to help people who had untreated MS for many, many years? 🤕
There will probably always be people like me, outliers, who have been denied healthcare. Because of where we are in the world (Yorkshire in my case...), our socioeconomic status, and abuse by family and doctors. What of us?
I like the term SAW and that it rhymes with RAW is a bonus. At the end of the day it's the same as old-fashioned 'progression' which always seems ironic as progression is usually taken to be a positive!
I was thinking about this newsletter in the middle of the night (probably because this time next week I'll be having dose #5). It's made me feel a bit low, TBH - but I guess this is the risk we take when we try to read as much as possible about our condition: it can occasionally dent the optimism that feels integral to living well with MS.
Anyway, I'll try to shake off the blues and look at this pragmatically: do other patients understand my hypothetical reluctance to de-risk to a less effective therapy (e.g. teriflunomide), because then I might not be able to access highly effective therapies in future? When it's being drummed into our heads to hit MS hard, it feels like a strange decision to actively make. Similarly, it's also crossed my mind: in future, would I be less likely to be able to access BTKis if I de-risked?
(On another note: it's the cancer risk that makes me feel apprehensive about L/T ocrelizumab use. Am I naive to presume that there's some central database which is keeping tabs on this data....?!)
Speaking of BVL....what about this recent study?
https://pubmed.ncbi.nlm.nih.gov/37148240/
Prof G,
I have convinced my centre to switch me from Ocrevus to Lemtrada following your articles.
Do you think alemtuzumab has, in a young person, early in their diagnosis, the potential to stop smouldering MS and BVL?
Or, do you think it is merely the best available option that simply *may* impact smouldering MS (I.e. would it be better to hold out on Ocrevus and wait for BTKis?)?
Thanks for all your work.
Great stuff. You had enthusiastically highlighted NfL testing very recently…can you share some thoughts regarding the degree of importance would you assign to sNfL testing results following a decision to de-risk an individual? As important as MRI, perhaps? Annually? Finally…any enthusiasm regarding plasma GFAP testing in addition?
I like SAW, because that’s exactly where I am. NEID and extremely frustrated not to mention getting worse. NEID does not mean “cured” now go away, end of, although that’s the standard of treatment, if you want to call it that. We can have huge flares with NEID and nothing to turn to. It’s a terrible situation for those who have been fortunate enough to achieve first rate responses to good DMTs only to lose what you’ve gained or progress you’ve made. You’re “cured” because the goal is NEID? No you’ll be SAW!!
“I am predicting relative to teriflunomide as a class, BTKIs will reduce disability progression by about 45% (range 40-60%).” Doesn’t sound that impressive to me! Would you be happy knowing that your brain / spinal cord was still being shredded (albeit slightly slower) despite being on anti-CD20 and BTKi therapies? What’s needed to ‘stop’ disability progression ie 100%? Will anti-virals make a greater impact on reducing disability progression?
Does mavenclad not target both b and t cells?
I agree with you prof G. Lesions are not the heart of MS. Maybe the real MS is the "thing" that drives progression in PPMS or non active SPMS patients (who have or dont have lesions but still their MS is progressing). I really would like BTK be very effective in PPMS. There are limited options for patients with this form :-( Do you think that BTK can be effective in PPMS? Or not because in this form people have antibodies in CSF which can drive their MS?