Many people with multiple sclerosis on ocrelizumab or rituximab are wanting to switch to another disease-modifying therapy. In this Newsletter I explain why and how to do it.
Would it be possible to have a link at the bottom of each MS-Selfie newsletter to a simple glossary of terms. For example, I don't know what an 'anti-CD20' is.
I mention all three in the Newsletter. They are rituximab, ocrelizumab and ofatumumab. They deplete B cells by binding to CD20 on the surface of B cells.
Just did a search through the newsletter for 'anti-CD20'. Their mentions are scattered throughout the newsletter. I don't recall seeing the explanation re. depletion, binding and B cells. Sorry to labour the point, but I would rather an easy go-to place (i.e. glossary) which immediately answers my question, rather than searching the newsletter and then breaking out to Google in order to put piece together fragments of my desired answer. Time is precious.
These newsletters assume some background knowledge. For example, if you are on an anti-CD20 I hope someone has explained how it works. In time I will do newsletters on each class of DMT so it will become clear.
My problem is making time to write the newsletters.
I’m really intrigued about so many people being misdiagnosed with MS. Are there other conditions that actually cause lesions on the spinal cord and brain? What are they?
The commonest are conditions such as neurosarcoidosis, vasculitis, neuromyelitis optical spectrum disorder or NMOSD, lupus and other autoimmune diseases.
Ocrevus is due in 5 weeks. Boosters for covid will start around September they say. Have already had the 2covid jabs and I am taking it as won't have made much of, if any kind of response to them. Are you saying we could postpone Ocrevus, get the booster, and then how long for the Ocrevus? The due dose will be my 2nd full dose at the same time. TIA
You will need to speak to your neurologist. PwMS on ocrelizumab seem to make T-cell responses to the vaccine, just not very good antibody responses. The T-cell responses may be sufficient to protect you against getting COVID-19 and severe COVID-19.
After 3 days of trying, spoke to an MS nurse who says there is no point in postponing Ocrevus as already on it and that they don't know when the boosters will be starting/given out anyway. Says am at no higher risk than everyone else, because I have had the 2 covid jabs and that I should be out and about living, seeing friends and family. I'm a tad stunned to be honest, I mean what the heck? Surely they must have some idea by now that Ocrevus and Fingolimod users don't make much if any response to the covid jabs?
I tried telling her I read stuff about MS from a Professor and the Ms Blog, I don't even bother with the rubbish the big charities push out. I'd love to send them the link, but it's took 3 days to pin them down to a phone call and the neuro doesn't speak to patients unless urgent. Not to mention I had an MRI in May and have no idea what the results were.
Hi, you wrote that "when someone fails a high efficacy DMT such as an anti-CD20 therapy it is always reasonable to take a step back and review the MS diagnosis".
I was diagnosed in January 2016, and since then have had 8 relapses (3 of them Optic Neuritis) treated with high dose Solu-Medrol: 4 while on Tecfidera, 3 while on Ocrevus. Even if we overlook the first relapse that occured 3 months after starting Ocrevus, it seems that this DMT not as efficient as it should be. NMO test I did a few years ago was negative. Should I be tested for MOG? Is it better to be treated with plasma infusions? What did you mean by taking a step back? What other diseases can cause relapses and clearly not be affected by both Tecfidera and Ocrevus?
Step back means rethinking and reviewing the diagnosis. I assume you are B-cell depleted and you have been checked for anti-drug antibodies that can prevent ocrelizumab working.
Thank you so much for your quick reply. I learned so much from following you on Twitter and reading your posts here. My answer is, sadly, no to both tests. I live in Israel, and these tests are not done here.
As I said there are many reasons why someone with MS may want to switch from an anti-CD20; it is not only about the efficacy and short-term safety of anti-CD20 therapies. I can imagine someone in your situation wanting to do something about vaccines. This is why MS and the practice of neurology is an art and not a science.
I am switching right now. I was on Mayzent for over a year and my white counts, all of them tanked so low i was helpless against anything. I had a series of things that happened all within a 2 week span of time than convinced me to stop taking it... First, i I managed to catch and rip a fingernail off and it went down tot he quick and bled. this led to an infection of the cuticle. It took literally 6 weeks to get that cleared up. While that was going on, i had already been switching things around in my diet to eat healthier so granola instead sugary cereals were added to my diet and i managed to crack a tooth.. ugh. It immediately became accessed. I saw my primary care doc on a Saturday who prescribed 2,000,g of penicillin a day for 10 days to knock the infection down so i could see a dentist. I had no response to this. NONE. whatsoever. nothing. While i was on this antibiotic, i developed a huge pimple up inside one of my nostrils.. when i say huge i mean it was so large it blocked the entire nostril. I have never had anything like that before in my life and I am 63 years old now. so yeah. I decided to stop take the Mayzent to heal my body. The tooth is better, the nostril is clear, the cuticle is healed and my skin is starting to clear up as well.. that's another thing i was having issues with the entire time I was on the the Mayzent. My skin.,. pimples everywhere.. all over my face.. down my neck, across my chest.. It was maddening.. It was like i was 14 again and going thru puberty.. My lymphocytes were as low as 420 which is way too low.. and over all white counts as low as 3500.. nope not doing that again.. looking to start on Copaxane soon. Had been on Aubagio just prior to Mayzent and had 3 relapses and saw quite a bit of progression on that so this is my last choice i guess
Not in my opinion. I can't imagine living with B-cells indefinitely. At some stage, we are going to have to derisk anti-CD20 therapies, particularly in older patients (>50).
I have a question about smoldering MS. From my readings of the medical literature as a person with MS, my understanding was that smoldering MS appears to be linked to brain volume loss and that a recent study suggests that Ocrevus might do a good job controlling for brain volume loss. I suppose my question is, do we really know at this point that one DMT is better than Ocrevus in this regard?
I think alemtuzumab, HSCT and natalizumab are superior to anti-CD20 therapies at slowing down brain volume loss. The confounder is disease duration and age. The results for cladribine look excellent in patients with CIS but less so in patients with longstanding established MS. The S1P modulators and teriflunomide also have a positive effect. The data on interferons (excluding IM interferon-beta-1a), glatiramer acetate and DMF are less convincing. WIth DMF the studies were underpowered for looking at brain volume changes.
Nope, Ocrevus only has a modest impact on BVL. We definitely know that it's worse than HSCT, Lemtrada, and Tysabri (HSCT and Lemtrada both seem to completely normalize BVL, i.e., bring it back to within the normal adult range). I think it's worse than Mavenclad too although I'm not sure about that one.
Mavenclad was offered to me at the same time that Mayzent was. I chose Mayzent because of the higher cancer risks associated with Mavenclad. So many people, including my son, have died in my family from cancer I felt there is just no way I was going to go with a drug KNOWN to increase the risk...
I’m in the opposite position, just about to transfer from Tecfidera onto ocrevus as active mri and 2 relapses in 6 months. Asked about capaxone but was strongly advised to go for a stronger DMT either - gilenya, cladribine or ocrevus. Trying to pick the best of a bad bunch as cancer is always a concern.
This post doesn't discuss going the other way, i.e. switching to anti-CD20 therapy. Going from DMF (Tecfidera) to an anti-CD20 therapy is relatively straightforward unless you have lymphopaenia. Even if your lymphocyte counts are relatively normal we have a few patients drop their lymphocyte counts after the switch. I suspect this is because most people on DMF have a relative lymphopaenia and anti-CD20 drops both B-cell and T-cell numbers.
Another aspect is the zoster risk might be higher when switching from DMF to an anti-CD20 because CD8+ T-cells are relatively low on DMF and drop further after dosing with an anti-CD20.
“Please note if you are NEIDA (no evident inflammatory disease activity) and you are getting worse in terms of disability progression, you probably have smouldering MS.” What’s the current state of play re promising trials to address smouldering MS? Barts have Sizomus and DoDo (perhaps others), are other research teams / pharma doing anything similar ie testing therapies to address smouldering MS?
Yes. BTKi may work on smouldering MS as they target microglial and macrophage activation, masitinib and ibudilast are going forward in phase 3 trials. In the UK we are doing the MS-STAT2 (simvastatin) and OCTOPUS trials. There are also trials of antivirals in MS that could be argued tackle smouldering MS. This list is long.
I read something recently about BTKi therapy and it sounds very promising.. I do have high cholecterol and high BP since stopping the Mayzent. I may ask my doc to start me on the simvastatin. I have taken that one before years ago. Going to research that more to present an argument to her.. thanks
I’m 69 years old and have been on Ocrelizumab for the past three years for my PPMS. At what point (age) should I stop taking infusions. My MRI’s show nothing new or increasing. I am seeing a lot of progression, probably age related.
I believe you had hypothesized in the past that OCB- folks may have less positive effect than those who are OCB+. I believe OCB- had even been disallowed in the trials. Any thoughts regarding that now? Data?
Also...I am a fast re-populator of B-cells. Doc recommends a switch to RTX at 2000mg. I say meh...for one, pandemic. Another...I think you had theorized OCR might be 6x the strength of RTX?
OCB-ve MS behaves in a more benign way compared to OCB+ve MS. Because OCB+ve implies B-cell involvement in the anti-CD20 (ocrelizumab) PPMS trial being OCB+ve was a requirement to participate in the trial. Therefore we don't know if OCB-ve patients with PPMS respond to ocrelizumab or not and hence I would be reluctant to expose them to the drug and its risks without knowing its benefits.
Yes, gram for gram ocrelizumab is a more potent B-cell depleter. We don't know how ocrelizumab or rituximab does in OCB-ve MS as they have not been studied in these populations.
My first full (and my last as I have quit due to new and worsening symptoms) was August 2020 and as of June 2021, my B cells are at 0.10. I haven’t gotten the COVID vaccine for that reason. I’m home alone all day and can’t afford the risk of a bad reaction. In two months, I anticipate having someone home with me and then I’ll get vaccine.
Would it be possible to have a link at the bottom of each MS-Selfie newsletter to a simple glossary of terms. For example, I don't know what an 'anti-CD20' is.
I mention all three in the Newsletter. They are rituximab, ocrelizumab and ofatumumab. They deplete B cells by binding to CD20 on the surface of B cells.
Just did a search through the newsletter for 'anti-CD20'. Their mentions are scattered throughout the newsletter. I don't recall seeing the explanation re. depletion, binding and B cells. Sorry to labour the point, but I would rather an easy go-to place (i.e. glossary) which immediately answers my question, rather than searching the newsletter and then breaking out to Google in order to put piece together fragments of my desired answer. Time is precious.
These newsletters assume some background knowledge. For example, if you are on an anti-CD20 I hope someone has explained how it works. In time I will do newsletters on each class of DMT so it will become clear.
My problem is making time to write the newsletters.
Thank you so much for all that you do.
I’m really intrigued about so many people being misdiagnosed with MS. Are there other conditions that actually cause lesions on the spinal cord and brain? What are they?
The commonest are conditions such as neurosarcoidosis, vasculitis, neuromyelitis optical spectrum disorder or NMOSD, lupus and other autoimmune diseases.
Ocrevus is due in 5 weeks. Boosters for covid will start around September they say. Have already had the 2covid jabs and I am taking it as won't have made much of, if any kind of response to them. Are you saying we could postpone Ocrevus, get the booster, and then how long for the Ocrevus? The due dose will be my 2nd full dose at the same time. TIA
You will need to speak to your neurologist. PwMS on ocrelizumab seem to make T-cell responses to the vaccine, just not very good antibody responses. The T-cell responses may be sufficient to protect you against getting COVID-19 and severe COVID-19.
thank you...what would you do if it was one of your patients?
Listen to them. It is their decision, not mine.
After 3 days of trying, spoke to an MS nurse who says there is no point in postponing Ocrevus as already on it and that they don't know when the boosters will be starting/given out anyway. Says am at no higher risk than everyone else, because I have had the 2 covid jabs and that I should be out and about living, seeing friends and family. I'm a tad stunned to be honest, I mean what the heck? Surely they must have some idea by now that Ocrevus and Fingolimod users don't make much if any response to the covid jabs?
Why don't you refer them to this site or send them the following reference:
Giovannoni G, Hawkes CH, Lechner-Scott J, Levy M, Yeh EA, Baker D. COVID-19 vaccines and multiple sclerosis disease-modifying therapies. Mult Scler Relat Disord. 2021 Jul 18;53:103155. doi: 10.1016/j.msard.2021.103155. Epub ahead of print. PMID: 34358943; PMCID: PMC8286545.
I tried telling her I read stuff about MS from a Professor and the Ms Blog, I don't even bother with the rubbish the big charities push out. I'd love to send them the link, but it's took 3 days to pin them down to a phone call and the neuro doesn't speak to patients unless urgent. Not to mention I had an MRI in May and have no idea what the results were.
Hi, you wrote that "when someone fails a high efficacy DMT such as an anti-CD20 therapy it is always reasonable to take a step back and review the MS diagnosis".
I was diagnosed in January 2016, and since then have had 8 relapses (3 of them Optic Neuritis) treated with high dose Solu-Medrol: 4 while on Tecfidera, 3 while on Ocrevus. Even if we overlook the first relapse that occured 3 months after starting Ocrevus, it seems that this DMT not as efficient as it should be. NMO test I did a few years ago was negative. Should I be tested for MOG? Is it better to be treated with plasma infusions? What did you mean by taking a step back? What other diseases can cause relapses and clearly not be affected by both Tecfidera and Ocrevus?
Step back means rethinking and reviewing the diagnosis. I assume you are B-cell depleted and you have been checked for anti-drug antibodies that can prevent ocrelizumab working.
Thank you so much for your quick reply. I learned so much from following you on Twitter and reading your posts here. My answer is, sadly, no to both tests. I live in Israel, and these tests are not done here.
- hypogammaglobulinaemia still within safe limits, no problems with tolerability, not getting worse, no evident inflammation
Is there a case to consider switching?
As I said there are many reasons why someone with MS may want to switch from an anti-CD20; it is not only about the efficacy and short-term safety of anti-CD20 therapies. I can imagine someone in your situation wanting to do something about vaccines. This is why MS and the practice of neurology is an art and not a science.
I am switching right now. I was on Mayzent for over a year and my white counts, all of them tanked so low i was helpless against anything. I had a series of things that happened all within a 2 week span of time than convinced me to stop taking it... First, i I managed to catch and rip a fingernail off and it went down tot he quick and bled. this led to an infection of the cuticle. It took literally 6 weeks to get that cleared up. While that was going on, i had already been switching things around in my diet to eat healthier so granola instead sugary cereals were added to my diet and i managed to crack a tooth.. ugh. It immediately became accessed. I saw my primary care doc on a Saturday who prescribed 2,000,g of penicillin a day for 10 days to knock the infection down so i could see a dentist. I had no response to this. NONE. whatsoever. nothing. While i was on this antibiotic, i developed a huge pimple up inside one of my nostrils.. when i say huge i mean it was so large it blocked the entire nostril. I have never had anything like that before in my life and I am 63 years old now. so yeah. I decided to stop take the Mayzent to heal my body. The tooth is better, the nostril is clear, the cuticle is healed and my skin is starting to clear up as well.. that's another thing i was having issues with the entire time I was on the the Mayzent. My skin.,. pimples everywhere.. all over my face.. down my neck, across my chest.. It was maddening.. It was like i was 14 again and going thru puberty.. My lymphocytes were as low as 420 which is way too low.. and over all white counts as low as 3500.. nope not doing that again.. looking to start on Copaxane soon. Had been on Aubagio just prior to Mayzent and had 3 relapses and saw quite a bit of progression on that so this is my last choice i guess
Can anti-CD therapy be a lifelong treatment? And what about de-escalation to a first line treatment like interferon?
Not in my opinion. I can't imagine living with B-cells indefinitely. At some stage, we are going to have to derisk anti-CD20 therapies, particularly in older patients (>50).
I have a question about smoldering MS. From my readings of the medical literature as a person with MS, my understanding was that smoldering MS appears to be linked to brain volume loss and that a recent study suggests that Ocrevus might do a good job controlling for brain volume loss. I suppose my question is, do we really know at this point that one DMT is better than Ocrevus in this regard?
I think alemtuzumab, HSCT and natalizumab are superior to anti-CD20 therapies at slowing down brain volume loss. The confounder is disease duration and age. The results for cladribine look excellent in patients with CIS but less so in patients with longstanding established MS. The S1P modulators and teriflunomide also have a positive effect. The data on interferons (excluding IM interferon-beta-1a), glatiramer acetate and DMF are less convincing. WIth DMF the studies were underpowered for looking at brain volume changes.
Nope, Ocrevus only has a modest impact on BVL. We definitely know that it's worse than HSCT, Lemtrada, and Tysabri (HSCT and Lemtrada both seem to completely normalize BVL, i.e., bring it back to within the normal adult range). I think it's worse than Mavenclad too although I'm not sure about that one.
Mavenclad was offered to me at the same time that Mayzent was. I chose Mayzent because of the higher cancer risks associated with Mavenclad. So many people, including my son, have died in my family from cancer I felt there is just no way I was going to go with a drug KNOWN to increase the risk...
I’m in the opposite position, just about to transfer from Tecfidera onto ocrevus as active mri and 2 relapses in 6 months. Asked about capaxone but was strongly advised to go for a stronger DMT either - gilenya, cladribine or ocrevus. Trying to pick the best of a bad bunch as cancer is always a concern.
This post doesn't discuss going the other way, i.e. switching to anti-CD20 therapy. Going from DMF (Tecfidera) to an anti-CD20 therapy is relatively straightforward unless you have lymphopaenia. Even if your lymphocyte counts are relatively normal we have a few patients drop their lymphocyte counts after the switch. I suspect this is because most people on DMF have a relative lymphopaenia and anti-CD20 drops both B-cell and T-cell numbers.
Another aspect is the zoster risk might be higher when switching from DMF to an anti-CD20 because CD8+ T-cells are relatively low on DMF and drop further after dosing with an anti-CD20.
“Please note if you are NEIDA (no evident inflammatory disease activity) and you are getting worse in terms of disability progression, you probably have smouldering MS.” What’s the current state of play re promising trials to address smouldering MS? Barts have Sizomus and DoDo (perhaps others), are other research teams / pharma doing anything similar ie testing therapies to address smouldering MS?
Yes. BTKi may work on smouldering MS as they target microglial and macrophage activation, masitinib and ibudilast are going forward in phase 3 trials. In the UK we are doing the MS-STAT2 (simvastatin) and OCTOPUS trials. There are also trials of antivirals in MS that could be argued tackle smouldering MS. This list is long.
I read something recently about BTKi therapy and it sounds very promising.. I do have high cholecterol and high BP since stopping the Mayzent. I may ask my doc to start me on the simvastatin. I have taken that one before years ago. Going to research that more to present an argument to her.. thanks
Is there any indication that cladribine might help counter smouldering MS?
Yes, this is why we are exploring it in more advanced MS with our Chariot-MS trial.
I’m 69 years old and have been on Ocrelizumab for the past three years for my PPMS. At what point (age) should I stop taking infusions. My MRI’s show nothing new or increasing. I am seeing a lot of progression, probably age related.
You should discuss this with your HCP. But the risks of infections increase with time. There are potentially safer DMTs you can be on at 69.
Thank you, I will. I’m trying to save my hand functions and thought Ocrevus was the only thing approved for PPMS.
Difficult. The problem is we don't really know if ocrelizumab works in people of your age as the was an age cutoff of 55 in the trial.
I believe you had hypothesized in the past that OCB- folks may have less positive effect than those who are OCB+. I believe OCB- had even been disallowed in the trials. Any thoughts regarding that now? Data?
Also...I am a fast re-populator of B-cells. Doc recommends a switch to RTX at 2000mg. I say meh...for one, pandemic. Another...I think you had theorized OCR might be 6x the strength of RTX?
OCB-ve MS behaves in a more benign way compared to OCB+ve MS. Because OCB+ve implies B-cell involvement in the anti-CD20 (ocrelizumab) PPMS trial being OCB+ve was a requirement to participate in the trial. Therefore we don't know if OCB-ve patients with PPMS respond to ocrelizumab or not and hence I would be reluctant to expose them to the drug and its risks without knowing its benefits.
Yes, gram for gram ocrelizumab is a more potent B-cell depleter. We don't know how ocrelizumab or rituximab does in OCB-ve MS as they have not been studied in these populations.
My first full (and my last as I have quit due to new and worsening symptoms) was August 2020 and as of June 2021, my B cells are at 0.10. I haven’t gotten the COVID vaccine for that reason. I’m home alone all day and can’t afford the risk of a bad reaction. In two months, I anticipate having someone home with me and then I’ll get vaccine.