The retrospective application of eligibility criteria is not a universally accepted principle. I am interested to know if you agree with this principle?
This is a pertinent post for me and an issue that i have rasied previously. I am in a similar boat to this patient. 2 years on ocrelizumab, chasing an IRT but getting limited traction without MRI evidence. The difference between us is that i have been on Ocrelizumab since diagnosis but i consider that my diagnosis was delayed for 4 years having being categorised as CIS in 2015, incorrectly in my view. Applying this logic, i would have qualified for alemtuzumab in 2015 - so can the eligibility criteria be applied in the same way? my neurologist says not. Perhaps i shouldnt have used up my second opinion seeking HSCT and come to Barts instead. The flexibility with which the criteria is applied is correct in my view but it feels unfair when you're on the wrong side of it
Nothing more than what we already do for each option.
Monthly for alemtuzumab up to 4 years after last course.
For oral cladribine before initiating the second course in year 2 and 2 and 6 months after start of treatment in each treatment year. The EMA/MHRA suggest that if the lymphocyte count is below 500 cells/mm³, it should be actively monitored until values increase again. I am not sure I agree with the latter, because what are you going to do about it? I only do tests if I can act on the result.
I asked to switch from ocrelizumab to cladribine following an abnormal smear test. I thought this was a sensible idea to give my body some time to ideally get rid of HPV without chronic immunosuppression, so was a bit annoyed to find I wouldn't be eligible. Maybe I should push further on this next time I see my neurologist. Surely cheaper for the NHS than treating an HPV-related cancer in 10 years...
How many people could have had different lives (myself included) if other options had been offered and explored earlier?? I think one has to live in the present and woulda,coulda, shoulda Is not a helpful approach. Of course one once the best option and the least amount of disability. But sometimes things don’t work out. Surely there needs to be something like “a statute of limitations“statute of limitations." That said I believe the medical community has a responsibility to stop being so arogant when deciding treatment options. My neurologist has never felt like a partner in my MS. I don’t believe any of the decisions were made with any understanding of what living with MS is actually like. M any understandin of what living wit MS is actually like.
Re: "How many people could have had different lives (myself included) if other options had been offered and explored earlier?"
I suspect the majority of pwMS would have different lives if they had other treatment options. In most countries the maintenance-escalation paradigm dominates it takes close to a decade for these people to get to get to a efficacy therapy and by then it may be too late to impact on the processes driving smouldering MS.
As someone that has had extreme side effects with a high efficacy DMT, which forced me to decide to stop taking the drug, I would have to agree with you on this one, absolutely. Also, in the minds of my neurologist and nurse practitioner, I am actually going backward by moving to Aubagio now since coming off of Mayzent. I do, however, wish to avoid the same circumstances I found myself in with the Mayzent. It completely tanked my immune system. I mean completely, as in super low over all white counts, absolute lymphocytes barely hovering around 400 and even tho mostly isolated, I found myself sick a lot and miserable with many opportunistic infections no matter how careful I was. I am unwilling to risk Mavenclad due to my family history of cancers (everyone has died of it except my father who died of a stroke at a young age) and apparently my MS is still very much active even when I was on the Mayzent as evidenced by MRI's and 2 relapses in 15months time. Unfortunately for me, I am in the USA and won't be able to get Medicare to pay for the HSCT anytime soon. Unfortunately, in less than a year I gained some 20 brain lesions, 3, brain stem lesions and 4 cervical spine lesions. My MS is very active and I am struggling. I am starting the Aubagio in hopes of slowing it and praying the HSCT will be made available here sometime soon for people like me. I am 64.. So that alone might preclude me from being eligible for that even.. which I also disagree with, but I have no control over it. excuse me for the non-sensical adage but I feel a lot like i am shoveling dung against the rising tide a lot of the time.. So many rules and regulations and the applications of them hardly seem fair a lot of times
Sorry to hear about your experience on siponimod. Dare I ask how old you are? Most people who get recurrent infections with continuous immunosuppression are older.
By the way I don't agree with the FDA's call on cladribine (Mavenclad) causing cancer. I have discussed this before. I really think the cancer signal we saw in the phase 3 programme was a false positive signal and the real-life data collected since then suggests there is no increased risk of secondary malignancy. The so-called SIR (standardise incidence rate) for cancers is just below 1.0 with quite tight confidence intervals. So don't let the black-box cancer warning put you off cladribine as an option.
I am now 64.. was 62 at start of the Mayzent and stopped after I had turned 63. I will research Mavenclad again, to look at any updated research they may have released on it. I also am positive for HSV so on these immuno-suppressants I am in a constant state of some type of outbreak, which is totally maddening. It gets so bad at times that I am unable to eat because of the weeping blisters around my mouth. Quite disgusting and painful as well as distressing, especially at my age
There is no reason why you can't go onto long-term antivirals for HSV infection. I have several patients who have been on acyclovir or preferably famciclovir for years to suppress either HSV or VZV.
valcyclovir doesn't seem to be working any longer.. I have an appt with primary doc on Tuesday this week. this is one of the questions I plan to discuss with her. Maybe a change in this medication will help because I am having steady outbreaks even while taking the medication. It's truly maddening.
I would warn her of the risk of sever IBS post alemtuzumab as a possible autoimmune risk. I know a bald middle aged guy who has been having alarming chest pain since February that has not responded to photon pump inhibitors. He has been feeling much better since last Friday ever since following the FODmap diet.
My understanding of the HSCT literature (not a doctor/scientist) is that patients without a history of strong immunosuppressant drug use had better results and tolerated the procedure better than those who were previously on heavy immunosuppressants. That to me seems at odds with the approach shown in your article which is that they require you to try these drugs before even being eligible for HSCT.
While it is a much more aggressive treatment, I really fail to understand why it has not been adopted in a more mainstream way as a first line option for those who want it. In the long run it is more effective and cheaper than paying for these expensive DMDs, most of which are taken for life at various intervals. My understanding is that HSCT risk is all front-loaded at the start and then essentially goes to zero if you make it out of the first 6-12 months without secondary complications.
I am actually on your side and agree with your arguments. I am fighting for AHSCT to become a 1st-line choice, but there are a lot of misconceptions about AHSCT including its long-term safety.
I have been offered Siponimod, to start in April. My question is , should I hold off the Siponimod till Hsct might become a first line option. I have smouldering MS, and a disability score of 7.5, but I still think I would benefit from it. I believe I’m worth it
Jenny most AHSCT guidelines have an upper EDSS score. In London it is 5.0 so I would be surprised if UK centre will offer it to someone with an EDSS of 7.5.
I believe the demographic of the majority of MS patients has had a lot to do with the very strict eligibility criteria for any Ms treatment. I am of course talking about female , post fertility, economic and social unimportance. Since Covid , there has been a plethora of research because it effects men very badly as well. MS has benefited by hanging onto the coat tails of said research discoveries. Sorry to sound like an angry feminist , which I’m not, but it seems abundantly clear to me that these drivers do exist. And thank you Prof GG for facilitating these sort of discussions .
Can I just clarify - when you mention "COVID-19 has highlighted long term safety issues with Ocrelizumab" are you referring to increased susceptibility to severe infections because of the immunosuppression or something additional? Thank you
I work completely normally as a frontline NHS healthcare professional on ocrelizumab. What are the benefits of switching? I’m in a very similar place to the person you write about. I don’t want to change however. Unless there are major benefits without incurring massive risks.
I 100% agree with retrospective application of eligibility criteria. I agree with anything that gives the patient more choice. It's our bodies, our brains, and our lives.
This is a pertinent post for me and an issue that i have rasied previously. I am in a similar boat to this patient. 2 years on ocrelizumab, chasing an IRT but getting limited traction without MRI evidence. The difference between us is that i have been on Ocrelizumab since diagnosis but i consider that my diagnosis was delayed for 4 years having being categorised as CIS in 2015, incorrectly in my view. Applying this logic, i would have qualified for alemtuzumab in 2015 - so can the eligibility criteria be applied in the same way? my neurologist says not. Perhaps i shouldnt have used up my second opinion seeking HSCT and come to Barts instead. The flexibility with which the criteria is applied is correct in my view but it feels unfair when you're on the wrong side of it
So would you monitor Lymphocyte subsets in this case post-treatment ? if so, how often?
Nothing more than what we already do for each option.
Monthly for alemtuzumab up to 4 years after last course.
For oral cladribine before initiating the second course in year 2 and 2 and 6 months after start of treatment in each treatment year. The EMA/MHRA suggest that if the lymphocyte count is below 500 cells/mm³, it should be actively monitored until values increase again. I am not sure I agree with the latter, because what are you going to do about it? I only do tests if I can act on the result.
I asked to switch from ocrelizumab to cladribine following an abnormal smear test. I thought this was a sensible idea to give my body some time to ideally get rid of HPV without chronic immunosuppression, so was a bit annoyed to find I wouldn't be eligible. Maybe I should push further on this next time I see my neurologist. Surely cheaper for the NHS than treating an HPV-related cancer in 10 years...
This poses a very interesting dilemma.
How many people could have had different lives (myself included) if other options had been offered and explored earlier?? I think one has to live in the present and woulda,coulda, shoulda Is not a helpful approach. Of course one once the best option and the least amount of disability. But sometimes things don’t work out. Surely there needs to be something like “a statute of limitations“statute of limitations." That said I believe the medical community has a responsibility to stop being so arogant when deciding treatment options. My neurologist has never felt like a partner in my MS. I don’t believe any of the decisions were made with any understanding of what living with MS is actually like. M any understandin of what living wit MS is actually like.
Re: "How many people could have had different lives (myself included) if other options had been offered and explored earlier?"
I suspect the majority of pwMS would have different lives if they had other treatment options. In most countries the maintenance-escalation paradigm dominates it takes close to a decade for these people to get to get to a efficacy therapy and by then it may be too late to impact on the processes driving smouldering MS.
As someone that has had extreme side effects with a high efficacy DMT, which forced me to decide to stop taking the drug, I would have to agree with you on this one, absolutely. Also, in the minds of my neurologist and nurse practitioner, I am actually going backward by moving to Aubagio now since coming off of Mayzent. I do, however, wish to avoid the same circumstances I found myself in with the Mayzent. It completely tanked my immune system. I mean completely, as in super low over all white counts, absolute lymphocytes barely hovering around 400 and even tho mostly isolated, I found myself sick a lot and miserable with many opportunistic infections no matter how careful I was. I am unwilling to risk Mavenclad due to my family history of cancers (everyone has died of it except my father who died of a stroke at a young age) and apparently my MS is still very much active even when I was on the Mayzent as evidenced by MRI's and 2 relapses in 15months time. Unfortunately for me, I am in the USA and won't be able to get Medicare to pay for the HSCT anytime soon. Unfortunately, in less than a year I gained some 20 brain lesions, 3, brain stem lesions and 4 cervical spine lesions. My MS is very active and I am struggling. I am starting the Aubagio in hopes of slowing it and praying the HSCT will be made available here sometime soon for people like me. I am 64.. So that alone might preclude me from being eligible for that even.. which I also disagree with, but I have no control over it. excuse me for the non-sensical adage but I feel a lot like i am shoveling dung against the rising tide a lot of the time.. So many rules and regulations and the applications of them hardly seem fair a lot of times
Sorry to hear about your experience on siponimod. Dare I ask how old you are? Most people who get recurrent infections with continuous immunosuppression are older.
By the way I don't agree with the FDA's call on cladribine (Mavenclad) causing cancer. I have discussed this before. I really think the cancer signal we saw in the phase 3 programme was a false positive signal and the real-life data collected since then suggests there is no increased risk of secondary malignancy. The so-called SIR (standardise incidence rate) for cancers is just below 1.0 with quite tight confidence intervals. So don't let the black-box cancer warning put you off cladribine as an option.
I am now 64.. was 62 at start of the Mayzent and stopped after I had turned 63. I will research Mavenclad again, to look at any updated research they may have released on it. I also am positive for HSV so on these immuno-suppressants I am in a constant state of some type of outbreak, which is totally maddening. It gets so bad at times that I am unable to eat because of the weeping blisters around my mouth. Quite disgusting and painful as well as distressing, especially at my age
There is no reason why you can't go onto long-term antivirals for HSV infection. I have several patients who have been on acyclovir or preferably famciclovir for years to suppress either HSV or VZV.
valcyclovir doesn't seem to be working any longer.. I have an appt with primary doc on Tuesday this week. this is one of the questions I plan to discuss with her. Maybe a change in this medication will help because I am having steady outbreaks even while taking the medication. It's truly maddening.
I would warn her of the risk of sever IBS post alemtuzumab as a possible autoimmune risk. I know a bald middle aged guy who has been having alarming chest pain since February that has not responded to photon pump inhibitors. He has been feeling much better since last Friday ever since following the FODmap diet.
Literature is silent on this topic it seems, save for this individual case: https://www.hilarispublisher.com/open-access/alemtuzumabinduced-inflammatory-bowel-disease-in-a-multiple-sclerosis-patient.pdf
Interesting. This is also new to me. However, IBS and IBD are very different entities.
agreed. All of this is DIY so far. Waiting for pooh test results from GP.
My understanding of the HSCT literature (not a doctor/scientist) is that patients without a history of strong immunosuppressant drug use had better results and tolerated the procedure better than those who were previously on heavy immunosuppressants. That to me seems at odds with the approach shown in your article which is that they require you to try these drugs before even being eligible for HSCT.
While it is a much more aggressive treatment, I really fail to understand why it has not been adopted in a more mainstream way as a first line option for those who want it. In the long run it is more effective and cheaper than paying for these expensive DMDs, most of which are taken for life at various intervals. My understanding is that HSCT risk is all front-loaded at the start and then essentially goes to zero if you make it out of the first 6-12 months without secondary complications.
I am actually on your side and agree with your arguments. I am fighting for AHSCT to become a 1st-line choice, but there are a lot of misconceptions about AHSCT including its long-term safety.
I have been offered Siponimod, to start in April. My question is , should I hold off the Siponimod till Hsct might become a first line option. I have smouldering MS, and a disability score of 7.5, but I still think I would benefit from it. I believe I’m worth it
Jenny most AHSCT guidelines have an upper EDSS score. In London it is 5.0 so I would be surprised if UK centre will offer it to someone with an EDSS of 7.5.
I believe the demographic of the majority of MS patients has had a lot to do with the very strict eligibility criteria for any Ms treatment. I am of course talking about female , post fertility, economic and social unimportance. Since Covid , there has been a plethora of research because it effects men very badly as well. MS has benefited by hanging onto the coat tails of said research discoveries. Sorry to sound like an angry feminist , which I’m not, but it seems abundantly clear to me that these drivers do exist. And thank you Prof GG for facilitating these sort of discussions .
Can I just clarify - when you mention "COVID-19 has highlighted long term safety issues with Ocrelizumab" are you referring to increased susceptibility to severe infections because of the immunosuppression or something additional? Thank you
Mainly blunted vaccine responses and increased severity/mortality in older patients with MS and/or comorbidities.
I work completely normally as a frontline NHS healthcare professional on ocrelizumab. What are the benefits of switching? I’m in a very similar place to the person you write about. I don’t want to change however. Unless there are major benefits without incurring massive risks.
https://gavingiovannoni.substack.com/p/case-study-switching-from-ocrelizumab?s=w
https://gavingiovannoni.substack.com/p/case-study-ocrelizumab-to-teriflunomide?s=w
https://gavingiovannoni.substack.com/p/case-study-switching-from-ocrelizumab-e79?s=w
https://gavingiovannoni.substack.com/p/case-study-switching-from-ocrelizumab-ee7?s=w
https://gavingiovannoni.substack.com/p/switching-from-an-anti-cd20-the-why?s=w
I 100% agree with retrospective application of eligibility criteria. I agree with anything that gives the patient more choice. It's our bodies, our brains, and our lives.