Good news for cladribine, not so good for ocrelizumab and fingolimod
Data has surfaced today at an International MS meeting on the impact of MS disease modifying treatments and it looks like it is supporting the biology. As presented by Dr Anat Archirion from Israel and as anticipated from past vaccination data, there was a poor (less than 20%) seroconversion (assessed using the Eurimmune Ig assay) with ocrelizumab and fingolimod, but cladribine showed good seroconversion. Information about other agents were not yet reported. The information was based on a sample of about 30-40 people and remember based on data that has emerged from the cancer field, people can make a T cell response despite, an inhibited B cell response. It remains to be seen whether this will happen in MS and also whether vaccinated individuals become infected. However, obviously this is a possibility. The result is consistent with the B cell hypothesis that we published some time ago. This needs to be confirmed, but as it is following what was predicted, it is likely this will be more or less confirmed. This will happen within the next month or so I suspect.
https://twitter.com/DrWBRO/status/1375176233579905026/photo/1
CoI. Multiple
However we have a different message coming from Sweden and sad to say this glass half-full message comes a bit late as the glass half-empty message above tends to make the take home message appear abit SH1. Hopefully the referees don’t read the blog or twitter, as it is under review. This looks at people who got infected with SARS-CoV-2 and makes the case that people make an antibody and T cell response and the response to vaccines will be great. But looking at that picture on twitter either rituximab is a lot less effective than ocrelizumab or the authors are in for a big shock. Indeed if you read the paper it is not as fluffy and lovely as you think.
So what does it say….First thing it suggests is that you are talking rituximab it may increases your risk of developing symptomatic COVID-19…This data was reported last summer on iWMS and profG did the stats and is some of the better data on this. They say in the study 89% of people had symptomatic covid by only 19% were seropositive. This is poor seroconversion as other people are showing. The difference here is that they argue that people with MS show poor seroconversion. However, that is not supported by the data in the story above. Next up, they say there is a T cell reponse and indeed there is a T cell response in some people especially if you seroconvert. but if you are sero(antibody negative) there is not much of a T cell response. Now read the abstract and that says that the idea that rituximab inhibits T cells by blocking antigen presentation is probably rubbish because here they would argue that antigen presentation isn;t blocked and you get a T cell response, but the actual data is not so clear cut in my mind.
B
This gives a bench mark about what baseline T and B cell responses look like, let’s see how they change after vaccination. I wonder if Sweden are using the Astrazeneca vaccine after all the Astra is Swedish.
Development of Humoral and Cellular Immunological Memory Against SARS-CoV-2 Despite B-Cell Depleting Treatment in Multiple Sclerosis. Cell Reports Medicine
B-cell depleting therapies are widely used as immunomodulating agents for autoimmune diseases such as multiple sclerosis. The possible impact of B-cell depletion on development of humoral and cellular immunity to viruses and specifically SARS-CoV-2 has raised concerns with the COVID-19 pandemic. We here determined humoral and cellular responses in participants of an observational trial comprising several multiple sclerosis disease modulatory drugs (COMBAT-MS; NCT03193866). Patients on B-cell depleting treatment, who previously had COVID-19-like symptoms, developed anti-SARS-CoV-2 antibodies and/or T-cell memory irrespective of their B-cell depletion status. Furthermore, antibody titres were similar to those observed with other treatments or controls, and anti-SARS-CoV-2 T-cells displayed functional similarity to controls producing IFN-γ and TNF. These results inform on the role of B- and T-cells in SARS-CoV-2 immunity and provide evidence that B-cell depleting therapy does not substantially abrogate SARS-CoV-2 immunological memory, in turn suggesting a low risk for reinfection and potentially responsiveness to vaccination.
This suggests great, the reality is not so great…..They have done so much work but too slow to publish, if it doesn’t get accepted now it will be time to rip it up and start again. Maybe if I had written it, it would have been more doom and gloom and the authors would not have to do a major, re-write as it looks like time to eat some humble pie or is this Kladdkaka.
A few questions as I try to understand this post. Does this mean that <20% developed antibodies, yet they may have a sufficient T cell response for protection? Would you expect this to hold true for Siponimod too? Is there a way to measure T cell response?
I take Siponimod and my neuro had me stop meds before and after each injection.
Yes less than 20% so from the ocrelizumab group it means about 10 people made antibodies and 30 people gave a response below background. I would say for fingolimod the data looked worse. People may have T cell response and also they may not. For fingolimod, siponimod, ozanimod and ponesimod it may be harder to answer the question about T cells as they are removed from the blood so where do you get the cells from, a lymph node biopsy. This should hold true for siponiod and the rest. If your neuro told you to stop dosing before and after perhaps they or the company making siponimod know something. Maybe there is a mitigation system. Fingolimod is removed very slowly so I suspect stopping makes no difference. Half disappears every 9 days, but for siponimod it is less than a day. Maybe by stopping it it allows the immune response to form, it takes 3-6 days for a T cell response to form and about 6 or more days for antibodies to form. Here the key is not to let disease reactivate or disease rebound will occur. So more for ProfK and to Joela to think about.
Yes you can measure T cell responses but it is not simple like measuring antibodies. You have to get cells and either stain them or give then the viral protein and detect their responses. An extralayer ofcomplexity for using fingolimod
Thank you for the reply and all of the information provided during this time.
I’m being followed by an infectious disease specialist in the US due to a minor reaction to the first injection. He has scheduled me antibody testing on April 28th, so I suppose I’ll find out soon enough. He is curious to see how I respond.
So are we let us know
Will there be data on the oral DMTs like Tecfidera, too?
I am sure there will be I’m sure. Im guessing it is unremarkable….but time will tell, they had people on most MS drugs and alot on dimethyl fumarate if I recall correctly
The data for the T cell response and anti-cd20 are confirmed for covid-19 infection, so hopefully vaccine response will be similar.
Not sure I understand. We know that vaccine can induce T cell responses but the question is will the T cell response also be suppressed? I am hopeful that you canmake aT cell response. There is data fromanti-CD20 in B cell cancers. They too failed to give a vaccine response (less than 20%) but 3/5 (60%) madeadetectable T cell response, meaning 40% didn’t. These numbers are too small.
https://papers.ssrn.com/sol3/papers.cfm?abstract_id=3796531
Preprint
Thanks I will post now
Sad times for those of us on anti CD20
So the question now is – working in the NHS can I really continue on a drug that means I will likely not be immune post-vaccine. Or will I have to change therapy….
😱😱😱 (nonverbal response)
I realise more tests need to be carried out on this but curious as to how we would proceed going forward in this new covid world. Apart from the anti vaxxers who do this by choice, I’m assuming we, (I’m on fingolimod) will still be vulnerable to covid and further more, still spreading it?
This is a possibility, I was rather shocked by the level of the fingolimod response it will be interesting to see if this occurs with other vaccines
I guess I’m also curious about why those Ocrelizumab seroconverters made a response and if that says anything at all about how or whether their treatment is working?
Can you help further translate this for us laypeople. Does this mean if you are on ocrelizumab and you got Pfizer you’re still 80% vulnerable to covid? Or something else.
Important to understand for those in this group because it impacts how far we can come of the bubble post vaccination while the world returns back to normal. Do these people then have to remain isolated until herd immunity?
80% of people produced no detectable antibody suggesting that those people go not benefit. Whether they make a T cell response is unknown, until that is known you have to assume that you have essentially not had the vaccine, unless you have had your antibody levels measured. Therefore you are as vulnerable as you were before you had the vaccine and therefore you should be cautious.
Thanks MD. This is not good news. But important for those of us on any cd 20 to know. Thanks for clarifying.
Le sigh….this is a bit depressing (I’m on Ocrevus). What is happening in the MSverse to learn more about the T cell response?
Thank you so much for the post and answering questions, straightforwardly. My wife halted Ocrelizumab 13 months before her first shot of Moderna, however, circumstances prohibited a blood panel previous to getting the shot so there is no way of knowing what values were present. Vaccination became available so she took it. After four weeks, the second shot completed her vaccination. She did feel crap for a couple of days after the second shot so perhaps, there was a desirable immune response (we hope).
This comment is extremely helpful to all who are in similar circumstances, ” 80% of people produced no detectable antibody suggesting that those people go not benefit. Whether they make a T cell response is unknown, until that is known you have to assume that you have essentially not had the vaccine, unless you have had your antibody levels measured. Therefore you are as vulnerable as you were before you had the vaccine and therefore you should be cautious.”
Thank you again! The information presented at this site is tremendously helpful and important to me and my loved ones. I am eternally grateful, as are many.
Wow 13 months….Clearly I have made the case that this may be OK because the memory B cells are depleted for so long, and your experience rather supports that view.
As to “There is no way of knowning”….It doesn’t matter about the before…We know what the negative level is…Get tested 2-4 weeks after second jab if you have a blood level then you are positive. I predict success. The median time to B cells back to the lower limit of normal for the cells, likely to respondm are about 62 weeks after three cycles and 72 weeks after 4 cycles. I believe Moderna probably gives the strongest antibody response.
Thank you, MD, you are a treasure! Hopefully, we can get a blood panel soon.
Checking my records, yes, it was 13 months (55 weeks precisely) from the last infusion of Ocrelizumab until the first Moderna shot. Prior to that last Ocrelizumab infusion was a period of 36 weeks to the previous infusion of it. Prior to that, the first four infusions had been spaced at 6 months, give or take a couple days. She has received a total of 6 full infusions counting the first split dose as one full infusion.
My wife’s exceptional neurologist, aware of our strong desire to do so, was willing to proceed with Ocrelizumab based on blood values (b-cells, etc.) rather than the calendar, thus the first 36-week gap between infusions. Then covid hit and we (spouse and I) decided to halt Ocrelizumab anticipating the benefit doing so might have toward effective vaccination. Other factors played into our decision, among them… she is age 66, demonstrates NEDA, plus we suspect booster shots of the covid vaccination will likely be required in the future.
If MS remains subdued, she does not anticipate further use of a MS DMT but would consider it, if need be. As back ground, my spouse received her first infusion of natalizumab in March of 2002, which was during the Phase 3 study. We know that because the study was unmasked and we were informed. She was on natalizumab continuously from 3/02 until 7/17 except for the brief period in 05 and 06 when Tysabri was pulled off market. Her health during those 15+ years was exceptionally good, in fact spectacularly good. She was on dose extension the last several years of Tysabri going 8 weeks between infusions with no ill effects. The only exacerbation, and it was severe, was during that brief period when Tysabri was off-market; she was on Avonex during that period. JCV titers were always high, usually between 2’s and high 3’s from the very first test when it was finally developed.
Her good health has continued during treatment with ocrelizumab but covid has pushed us into halting, at least for the time being, and assessing as conditions change and knowledge is gained.
Thanks for the info
Thanks for sharing this useful information. Please keep us posted about news concerning the T cell responses in people who do Ocrelizumab.
I am one of them (started the treatment w Ocrelizumab on July 2020). My neurologist and I are quite sure I had Covid on March 2020 (mild symptoms, such as fever for 1 day and a half, lost of taste and smell and some cough, and all the friends I was with 5 days before the outset of the symptoms also had such symptoms, or even worse), although I never did a PCR those days (due to the emergency situation those days and to the priority given to people having a sever form of Covid). I did a serological test 6 weeks after the start of the symptoms and it showed negative IGM and IGG (same with other serological tests done the subsequent months). My friends tested all positive to the IGG (which supports the assumption that I had Covid too). I had my last Ocrelizumab infusion on February 12, 2021 and I was recently contacted for the anti-covid vaccine (2 weeks ago). Following my neurologist’s advice, I did not get the vaccine yet – she told me to wait at least until mid May (i.e. 3 months after the last Ocrevus infusion). However, my work, age (35) and the city where I live (where social restrictions are not that strict) expose me to risk of contagious and I really can’t wait to feel less vulnerable. Should I keep following the advice to wait at least until mid-May or hope in the T cell (or to be in the lucky 20% who develop anti-bodies response to vaccine) and get vaccinated asap? Many thanks in advance to those who will take the time to answer.
Many people with no or mild symptoms do not make an antibody response but they make good T cell responses. If you have had COVID before you got ocrelizumab you should have T cells and bais of B cell response and this gets boosted with the vaccine
Thanks for your answer. However, I have to apologize, as I was wrong when I said that I had started Ocrelizumab on July 2020. I actually started it on July 2018. Therefore, when I (probably) had Covid (March 11, 2020) I was already on Ocrelizumab (i had done the infusion on January 20, 2020). Would change your answer? Many thanks and apologies again for the typo in my previous message!
You probably have a blunted antibody response but probably a T cell response
Thanks! I hope the T cells are still there (more than a year has passed) and in any case that the vaccine (that, as I said, I have been adviced to do no earlier than mid-May) will trigger them again! Please keep us posted about evidence of T cells responses. Many thanks again and congrats for the amazing knowledge sharing work you do through this blog. Very much appreciated.
So if someone had Hsct with ritixumab one year prior to vaccination with phizer, would they likely still have a blunted response?
It depends on who quick your B cells repopulate…rituximab is abit quicker than ocrelizumab