Bring back the experts

B

Barts-MS rose-tinted-odometer: ★★

“I think the people of this country have had enough of experts”, Michael Gove, June 2016.

Of the many positive things to come out of the COVID-19 pandemic and our response to it is the end of the era of denigrating the expert. Yes, expertise and in particular deep expertise really matters and that applies to the diagnosis and management of multiple sclerosis. 

What is the difference between expertise and deep expertise? For example, I am registered by the General Medical Council in the UK as a neurologist and hence a medical expert in the practice of neurology. This means I can see, diagnose and manage anybody with a neurological problem. However, my sub-speciality is multiple sclerosis and related diseases (deep expertise). If you had a myopathy or a disease of muscles would really want me to be your treating neurologist. I suspect not; you would probably want to see a neurologist who specializes in muscle diseases. Although, I can quite easily read about the latest evidence and research into myopathies and give you an expert opinion, as I don’t have the day-to-day experience (deep expertise) in managing patients with myopathy you would not be given the best advice. Who knows if my self-directed rapid myopathy update would be good enough?  Would I have enough insight and experience to only read the best most up-to-date evidence or would I be influenced by some whacky off-the-wall myologist (muscle expert)?

We need, more than ever, a serious pushback on ‘fake news sites’, ‘lobby groups with vested interests’, ‘social media groups without expert input’ and ‘anti-science movements with unsubstantiated conspiracy theories’ to name the most obvious.

We also need to understand and learn to live with and be comfortable with uncertainty. Yes, that means accepting that experts may disagree with each other. Science is not black-and-white and is usually grey and as more evidence emerges and innovations or ideas become adopted or accepted the colour or advice becomes closer to being black or white. Science and the acceptance of science take time.

This is where inspired leadership comes into play. In any field, there are leaders who have the necessary reputations and trust that people will follow their advice. These leaders are often good communicators and have the uncanny ability to provide a balanced view of the state of play when the evidence is not black-and-white and they can communicate uncertainty in a way that makes sense and is understandable to the general public. Dr Anthony Fauci, from the NIH, comes to mind with his level headed approach to the COVID-19 epidemic in the US. On the other hand, there are many examples of bad or poor leadership during this pandemic, which has resulted in squandering of political capital, confusion and lack of trust. I don’t think I need to give specific examples of poor leadership there are many obvious ones.

In the MS space, there is different advice being peddled by various groups about what to do about vaccinating people with MS on anti-CD20 therapies with the newly licensed or soon to be licensed coronavirus vaccines. I think there is broad consensus that a live replicating viral vaccine is a no-no in people on anti-CD20 therapies. However, this advice is irrelevant as the three coronavirus vaccines at the head of the queue are not live replicating virus vaccines. The Oxford-AstraZeneca vaccine uses a viral vector (chimpanzee adenovirus) to deliver the construct (nucleotide message) to express the immunogen, but it is a replication-deficient virus so is highly likely to be safe in people with MS on anti-CD20 therapies. 

Another bit of misinformation that is doing the rounds is that these vaccines will trigger MS relapses. This is based on extrapolating data on two non-peer-reviewed cases of CNS demyelination in the Oxford-AstraZenca (Ox-AZ) trial and several cases of transverse myelitis in patients who have had COVID-19. One case on in the Ox-AZ trial, who received the vaccine, had an initial attack or relapse and was subsequently diagnosed as having MS; i.e. assume because they had pre-existing lesions and were now shown to have a second attack or new lesions consistent with dissemination in time. The other case had an episode of vaccine-related transverse myelitis (TM), which is relatively common with vaccines in general. Please note that vaccine-related TM is not MS. The only vaccine that has been reported to potentially trigger MS relapse is the live yellow-fever vaccine and this is based on one report that has subsequently not been replicated. Therefore, there is no current evidence that coronavirus infection or coronavirus vaccines trigger MS relapse. This in my opinion is not a reason to avoid having the coronavirus vaccine at present. This opinion may change if new data emerges to the contrary.

Another bit of grey advice that is being peddled as black or white is that people with MS (pwMS) on anti-CD20 therapy should delay their next infusion or miss one or two infusions to allow B-cell reconstitution before they have a coronavirus vaccine. What is the evidence for this? There is no definitive evidence. Yes, I agree that in general people on anti-CD20 therapies have blunted antibody responses to wild-type SARS-CoV-2 infection and to other vaccines including vaccines with so-called neoantigens or new antigens that the immune system has not seen before. However, this doesn’t mean these people haven’t developed immunity to the infection of vaccine that is long-lasting. For one the vast majority of pwMS on an anti-CD20 therapy who get COVID-19 make an uneventful recovery. Why? Almost certainly this recovery is due to cellular and not humoral (antibody) immunity. Do you then think this cellular immunity simply vanishes? Highly unlikely. Normal people who have COVID-19 and who lose their antibody responses still have cellular immunity. My interpretation of this data is that pwMS who are on an anti-CD20 therapy should simply go ahead and have the coronavirus vaccine when it is offered to them and not to worry about whether or not they mount an antibody response. Whilst this is happening companies like Roche-Genentech (ocrelizumab & rituximab) and Novartis (ofatumumab) or the wider MS community should be funding studies to look at both antibody and cellular immunity to the coronavirus vaccines in pwMS on these therapies so that we can develop an evidence base. The data collected as part of these studies will not only be relevant to SARS-CoV-2 infections and vaccines but other infections and future vaccines. 

In my opinion, it is more important for pwMS to be vaccinated than to not be vaccinated. This is because vaccination policy is really about population, or subpopulation, health and stopping the spread of the virus and protecting the individual is a secondary aim. If you have MS and would rather wait for data to emerge on the safety and efficacy of the vaccine in the MS population it will take another 6 to 12 months, and maybe longer, and then the evidence if not collected prospectively as part of a well-controlled trial may not answer the questions you have. Also in 6-12 months, the pandemic is likely to be over and hence these questions may never get answered.  

So my gut feeling based on scientific principles is that all pwMS should be vaccinated. If the initial roll-out of vaccines means the vaccines may be rationed I would argue we prioritise pwMS (1) over the age of 50, (2) those with significant comorbidities, (3) those on immunosuppressive therapies, in particular, those on anti-CD20 therapies and natalizumab and (4) those pwMS doing essential jobs with significant face-to-face contact with the general public (healthcare workers, care workers, teachers, etc.) to get the vaccine first. 

Disclaimer: As I am not a public health or vaccine expert you need to interpret my advice with care.

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Twitter: @gavinGiovannoni                                  Medium: @gavin_24211

About the author

Prof G

Professor of Neurology, Barts & The London. MS & Preventive Neurology thinker, blogger, runner, vegetable gardener, husband, father, cook and wine & food lover.

55 comments

  • Thank you for this. It confirms my gut feel that I want the vaccine as soon as it is offered to me. I am a 55 year old with MS, on Ocrevus and very happy with it. From what I have read, it seems the immune response to the vaccine is attenuated, not non-existent and if there is something in my body that helps fight Covid, should I get it, then I will go with that. I would prefer NOT to delay my next O infusion and potentially leave me open to more relapses. (PS hope you recover well and fast from your accident).

  • It should be remembered that Michael Gove is a politician and he will always say what he thinks will win him the greatest number of votes, not what is in the public interest. Politicians haven’t banned cigarettes – even though virtually everybody recognises that it will benefit the public.
    The anti-vaxxer ethos, although unsubstantiated, is even being accepted by some doctors now. To anybody who believes that vaccines are harmful – smallpox to you. Yes, some vaccines cause harm. Take for example the old polio vaccine. It was a live oral vaccine added to a sugar cube and it caused polio in about 1:1,000,000. When the UK population’s likelihood of getting real polio fell to below 1:1,000,000 the vaccine was substituted for a safer conjugated form which cannot cause polio. I don’t know if this vaccine is more or less effective, or if it was more or less expensive, but it was changed to maintain benefit exceeding harm.
    It’s really difficult for anybody to know what truth is. This is related to time and understanding. When cigarettes were issued to military personnel, Doctors thought that they produced health benefits, but times have changed, evidence has accrued and nobody advocates tobacco for it’s health benefits. Here’s thought though; the harm from tobacco comes mainly from combustion (smoking). What would happen if tobacco were convection vaped at a maximum temperature of 220 centigrade?
    I hold a theory: EBV causes MS. Many who follow this blog will agree with me. The pharmaceutical industry sells expensive drugs to treat MS that only address this only indirectly. The status quo might be maintained because the pharmaceutical industry sponsor MS research trials and would be financially disadvantaged by finding a ‘cure’. Most consultants, and the ABN don’t believe this theory. Now it sounds like a conspiracy theory. How is anybody to know what is conspiracy theory and what is enlightenment that will one day become accepted understanding?

  • Two observations +:

    …1) Uncommon may be more common than we think it is- My lawnmower guy (out here in Lancaster County PA USA), with a matter of fact tone sounding like he is speaking with someone of equal opinions, says that he won’t get the covid vaccine because of the “chips” in it (computer chips, not potato chips). He also claimed to be cured of the virus in June with an infusion of vitamins and antibiotics. He’s dead serious with no apparent realization that what he is saying can be considered “wacko” and paranoid. He is an adequately intelligent guy with inadequate education.

    …2) I contribute frequently to the Biotin for Progressive MS blog on Facebook, where I am the resident negative naysayer who tries to combat out-of-control “placebo” minded individuals from misdirecting or misleading sincere MSr’s looking for help. Because it hasn’t helped me, they say, that doesn’t mean I should block others from helping themselves. There is a subgroup of people it helps, they say. And at this blog, big pharma controls everything to benefit the big guy or fails to recognize common sense. And if you read their comments, you might believe all this. I counter with as many bits of “fact ” as I can, including the recent SPI2 data. It is a group of individuals who have “morphed” the blog from it’s original intent when Biotin was still a question. If anyone is interested in seeing this phenomenon in real time, go see it for yourself at Facebook.

    …On a side note and not in the same spirit as the above, as to Ocrevus and vaccines- I was under the impression from what I was reading here, that Ocrevus may substantially block effectiveness of covid vaccines. So for example, a person 63, with several “half” comorbidities, and who is not seemingly progressing from active disease but rather no longer compensating as well, and who is exposed to the virus via habitat with an essential worker, and part time work himself with maskless idiots, he has put off or discontinued treatment with Ocrevus; as death is probably more severe than a painful limp. 35 yrs. maybe, 63 yrs. no, as there are additional factors in play; it is not simple. But science should rule the day and he always eagerly awaits definitive information.

    • 1.Full of SH1 then…Antibiotics are for bacteria they dont touch virus, if intelligent you could reason
      2. Ditto
      3. Get the vaccine, if it doesn’t work consider a boost. How long are you going to have to wait

      • But that’s the way many of the hard core conservatives “think”; it comes with chips either put in your skin or as part of the vaccine. The thinking is not that deep. (Just giving some examps of what Dr. G was talking about.) The Pfizer vacc will be approved in a couple days and the Moderna one week behind it. I anticipate 6 weeks (a guess), once things get rolling. I’m somewhere between top priority and low priority in the middle., my Doc says. You mention, MD, get a boost if the first dose doesn’t work. If the vaccines aren’t working for me that’ll mean I must have got the virus. But that’s not what is going to happen!

      • Re. ‘Antibiotics are for bacteria they dont touch virus.’

        Have you read the following?
        Topical antibiotic triggers unexpected antiviral response.
        Date: April 9, 2018
        Source: Yale University
        https://www.sciencedaily.com/releases/2018/04/180409112602.htm

        ‘A Yale-led research team made a startling discovery while investigating the effect of bacteria on viral infections. When they applied a common topical antibiotic to mice before or shortly after infection with herpes and other viruses, they found that the antibiotic triggered an antiviral resistance in the animals, the researchers said.’

    • 2. If someone gets benefits from placebo effect why take it away? It’s not like taking biotin is stopping these patients to seek better treatments – there is none. It doesn’t matter if you are correct or not, if revealing truth doesn’t help in both short term or long term just don’t do it.

      • Wow, here we go, on Dr. G’s website, no less! This post, by Dr. G, is about the benefits of medical expertise in the context of the necessity to take an important vaccine. I offered two examples of people failing to recognize medical expertise. And you’re advocating, “against” one of my examples, that the placebo effect is as good as the real thing, that science should be kept at bay and information manipulated, in order to protect the feelings of others in an otherwise helpless situation. We are to assume they have tried everything. And even if they haven’t, it makes no difference anyway. So best not to interfere with happy people fooling themselves. It’s almost cruel. Just let them do it. I didn’t know the Facebook site on Biotin was only for people trying to fool themselves and truth was to be avoided. It doesn’t say that. I am not convinced that all MSr’s are fully informed and have sought all possible options. So you are my example #3, behind #1 and #2 above. Should I continue?

        • The point is there is no real thing right now. And this has nothing to do with feelings – you need to understand placebo effect is real not in the imagination.

          • “”Don’t stop people from helping themselves. The studies show again and again there is a sub-group of people that Biotin works for. Don’t forget that science is frequently wrong. The pharmacy companies can’t make money from Biotin so they don’t represent people like me. The SPI2 study endpoints were too narrow and the study population skewed, so the new results mean nothing anyway.

            So no, Biotin works for me, it’s not a “placebo”. Now, don’t take the drug store brands as they are not enough, you need to special order it and take more. Don’t take it before a test. I have mine specially prepared at a specialty pharmacy because it works better for me that way. I can’t say where you should buy it, or how to identify the good stuff, or exactly what benefit you’ll get, or how much you need to take, or when you should take it, or how many months it’ll take to work, but you should give it a try. Remember, it works for me. Maybe you’re in the subgroup too and it will work for you as well. You don’t know unless you try.”” I hear they’re going to do bee stings again, with better “stings”.

            And that’s what you’re dealing with. Not good for MSr’s. Not good for science. No medical expertise; even anti. Spin it as you will.

    • Re: “Ocrevus may substantially block the effectiveness of covid vaccines”.

      Yes, and no (we don’t know). We know that pwMS on anti-CD20 therapies have a reduced antibody response to vaccines, but these reduced responses may still be sufficient to be protective. And then there is the cellular immune response arm that has not been studied in relation to vaccines in pwMS on anti-cd20 therapies.

      The other side of the coin is that it takes many months (at least 6 months and usually longer) for B-cell reconstitution to occur after stopping an anti-CD20. The latter not only depends on which agent you are on (rituximab, ocrelizumab or ofatumumab) but also the duration of treatment, your size and potentially other factors such as genetic variants, previous treatments, etc. So if you stop ocrelizumab or miss a dose the pandemic will be almost over.

      You take my advice, your HCP’s advice, your government’s advice or that from a FB group. There really is no right or wrong choice, but hopefully an informed choice.

      • Hello Dr. G. (You are not my doctor and I make my own choices based on best available information, most of which comes from other sources.) My last half infusion was in Sept ’19 and I was due for the full infusion on Fri the 13th (no less), in 3/2020. My doctor was away. I am probably non-active SPMS, yet slowly declining in R leg. I was following the news on covid at the time and it just didn’t sound good. So I opted out on my own. Learned later about the 6 mo. minimal period to recover B cells (if I have that right). So I would say yes, that would be a huge influence on a decision to stop Ocrevus (the wait time to normalcy and vaccine readiness), in addition to the consideration of where one is on MS disease activity. I am pretty happy knowing a vaccine ought work for me now (been more than a year since a half dose). But I’m not thrilled about my leg. At least soon I won’t have to worry too much about the maskless people, or my wife being an essential worker. So it’s like “5 of one (not 6) , and a half dozen the other”. This is not for you, Dr. G but for others who may have interest. Good Day, hope you’re approaching “getting back to normal”.

  • Where is the data!!!! It seems we are in the chicken or egg debate, i.e. which one came first? We need the data to be sure these vaccines are safe in pwms; however, in order to get the data (since Pharma is unwilling) the expectation is we take the vaccine and cross our fingers and hope for the best.

    By NO means am I anti-vaccine, I just want to see the safety and efficacy data for pwms first. My option is based on personal experience with Ocrevus….was told it was safe for 99% but then I had severe adverse reaction. Sorry, but my plan is to let the data emerge before I am willing to roll the dice.

    The drug companies state in their brochures they don’t even know how a particular DMT works, so how can we say with confidence the vaccines are safe in pwms without supporting data???? Speculation and hearsay is not scientific proof 😉.

      • I do not know, you are the research expert, so you tell me! At least 6 months, but I would be more comfortable with 2yrs of data.

        It just seems that your opinion has changed now that the U.K. has a vaccine in hand. Went from we need more data, to take the vaccine it seems safe. I am sorry for this and do not normally call you guys out, but……

        Prof G. From 11/7/20…” I am sure we haven’t heard the last on MS DMTs and vaccine readiness. This is why I would urge all the DMT manufacturers to do the necessary studies to provide us with the necessary evidence-base to make clinical decisions.”

        MD Comment on 7/11/20 post…”
        The live vaccines (Oxford, Sputnik Jansen) for COVID-19 cannot replicate and so cannot produce a productive infection, unlike attentuated live viruses so they are very different. The MS manufactureres need to get on this case ASAP. Indeed a case could be made that an attenuated immune respnse may be beneficial in allowing a strong response to be generated. Adenovirus does not integrate into the genome we call this episomal so it is lost in replicating cells. So a study needs to be done on this ASAP.”

        What happened to needing more data and research??

        • 2 more years of isolation/shielding?

          No my attitude has not changed I believe we should be collecting data from people with MS taking vaccines, but you have to make a start just as you do with trials. However if we collect the data we should be able to optimise advise. Will this happen?

          • Exactly, and when trials are being designed, certain populations are excluded. This is my point, not every pwms should immediately jump to get the vaccine.

            I clearly fall into the excluded population, since my responses to DMTs have been “abnormal”. It is just a personal decision. I hope many pwms bravely decided to take the vaccine and provide individuals like me with some data.

            And yes, two more years of strategic sheltering is feasible for me, socially and economically. I know many individuals do not have this luxury. However, I am a disabled veteran and work for the government, and can continue to provide public service from home. No kids and wife already worked from home before the pandemic.

            Thank you for clarifying the position of the barts team and the need for more data. I was a bit surprised by Prof. Gs post and tone today, so sorry for taking over the conversation.

            Maybe it might be best if I take a break from commenting for a while. I do not think many readers (or the barts team) care to hear my opinions. Keep up the good work and I will keep supporting you, just as an observer, as I was the first year following this blog.

            If anything interesting happens with my post ocrevus b-cell repopulation, iteri approach, or transition to clad in 2021, I will let the readers know.

            Interestingly, my b-cells went from 0, 2, 32, and now 10/ul, over a four month period. Started Teri at 0/ul, had a bad relapse at 32/ul, now it seems Teri is controlling my b-cells as they dropped to 10/ul. Will be testing EBV levels in January. Also, as my “new” b-cells repopulate post Ocrevus, they seem to be oddly programmed, per my immunologist. When my cd-19 were at 32/ul my cd-4 were off the chart (>3000/ul). When my cd-19 fell back to 10/ul, my cd4 had a corresponding decrease back to normal ranges. This is the most recent update I have regarding my situation. New daily base line pain level 8/10. EDSS 5.5 with use of a cane, and continuously seeing new cervical and brain lesions on 3 month scans using T3 MRI.

            I hope everyone has a nice holiday season and 2021. Be nice and spread positivity not hate.

          • ProfG and the health profession want use to get back to normal as quick and as best we can, to do this we have to take the plunge. Opinions are opinions and if we dont agree we can argue our case, profG has thick skin and challenging his view is not an issue. As for iteri, stopping effecive treatment and having new lesions suggests what ever you are doing is not working

    • Re: “Where is the data!!!!”

      The data on the safety and efficacy of the vaccines is there in the people without MS. We have to extrapolate it to pwMS and at the same time collect real-life data on the outcome. We live in democratic countries with libertarian values so you don’t have to have the vaccine. However, if you have the vaccine it will not only reduce your chances of dying from COVID-19 by two orders of magnitude, from say 1% (1 in a 100) to about 0.01% (1 in 10,000) but more importantly, it will stop you spreading the virus to other people, in particular the most vulnerable.

        • So what….the important issue is that you are more protected . Yes it is nice to think about your fellow human

          • Of course ;-).
            But pass on the virus despite of vaccine would mean that there’s possibly no end of pandemic and restrictions in sight. And do we know how much time the immunity after vaccine persists?
            But thanks for your work anyway. You make decisions much easier for me.

  • Tom H – so you’re happy to just wait for other people with MS to have it first and see what happens to them? Says a lot really! You want science and research to advance, you just don’t want to be the one doing it…

    I’m on ocrevus and working on the frontline and am extremely hopeful for dose 1 this side of Christmas. So what if it doesn’t work as well for me? Not having it at all will definitely not work, so I have nothing to lose!

    • Anonymous- You do not know me and have no right to question my character. Grow some balls and put your name on your comments.

      If MD would have posted a subsequent reply I sent, maybe you would understand my position.

  • Tom, I find your post bears repeating because many of us feel similarly, I believe. Expert opinion means a great deal to me but so does data and in a head to head its data by a nose. Perhaps the present time calls for a plunge we would normally not make but this one seems particularly foggy at the jump-off. I understand your discomfort and find your point well made…

    TOM H.
    December 6, 2020 at 4:48 pm
    “Where is the data!!!! It seems we are in the chicken or egg debate, i.e. which one came first? We need the data to be sure these vaccines are safe in pwms; however, in order to get the data (since Pharma is unwilling) the expectation is we take the vaccine and cross our fingers and hope for the best.

    By NO means am I anti-vaccine, I just want to see the safety and efficacy data for pwms first. My option is based on personal experience with Ocrevus….was told it was safe for 99% but then I had severe adverse reaction. Sorry, but my plan is to let the data emerge before I am willing to roll the dice.

    The drug companies state in their brochures they don’t even know how a particular DMT works, so how can we say with confidence the vaccines are safe in pwms without supporting data???? Speculation and hearsay is not scientific proof 😉.”

    • Re: “By NO means am I anti-vaccine, I just want to see the safety and efficacy data for pwms first.”

      The pandemic is likely to be over by the time we get sufficient data on pwMS in relation to both safety and efficacy of SARS-CoV-2 vaccines and even then the data may be poor and underpowered.

  • Thanks as always Prof G.

    I fit your demographic for being prioritised above. I’m due my next octelizumab on 5th January. I had an appointment with my neurologist on Friday and her advice was as yours to take the vaccine as and when it’s offered. If it’s offered this month I’ll push my infusion back by 6 weeks. If it’s not offered before 5th January I’ll go ahead with my infusion. How long do you think I should leave after my infusion to have the vaccine? Should I aim for nearer my next planned treatment in July?

    • Yes, thank you for offering your deep expertise, Prof G. I am grateful. It helps inform my personal decision. I may get offered access to Pfizer or moderna vaccine before end of year and I am scheduled for ocrevous infusion at end of January. Like Debbie, I am wondering about optimal timing between vaccine and infusion. Are there basic theories of immunology to guide dose spacing? Based on the current methods used for covid surveillance in the States, I think it very unlikely that there will be timely sufficient publicly available data on safety and efficacy for pwMS here. If a State or County refuses to publicly publish the total cumulative number of Covid Patients hospitalized in a region (a fact based statistical number), why should we anticipate publicly available data on pwMS’s response, adverse or otherwise? Will nursing homes take on the challenge of tracking vaccine response to co-morbidities? It is doubtful nursing homes will have the resources to keep such robust data. Neurologists will need to take the lead, and track response of vaccine in patients from their clinics. But isn’t this time wasted?

      • If you are on ocrelizumab and are not delaying your next dose the best time to take the vaccine is probably about 4 weeks before the next infusion, which will maximise some early deep tissue or lymph node B cell reconstitution to occur even if the peripheral B cell counts are still suppressed. The point I am making is that there will be about a 6- to 7-month window (December 2020 to June 2021) at a population level for the ‘MS population’ to derive the most benefit from the vaccines and to contribute the most benefit to society (stopping the spread of the virus). If your next-dose timings do not coincide with the availability of the vaccine to you I would recommend going ahead with the vaccine anyway.

        • Thanks Prof G, if my next infusion is 5th January and I’m NHS staff currently working from home do you think I should delay my next infusion? I know that nobody knows the exact timings of the vaccination roll out but I’d be gutted to miss it if I was due it mid Jan. My thinking then is that I would need to delay vaccination until late spring/early summer 6 weeks before my next infusion although you say 4 weeks is ok

          • Not ProfG here, but the answer is yes, i.e. in favour of waiting until you have the vaccine. Check with your team, of course.

          • Thank you so much Prof K. This is what I was thinking but it’s hard when you don’t know when you’ll get the vaccination. I am considered as vulnerable NHS so was hoping to be prioritised from what I’d heard but unsure now. Anybody got any idea re timeframe?

          • I would say no. We have no published peer-reviewed data that states that by delaying your next dose of ocrelizumab 1, 2, 3, …… 6 months will make any difference in terms of your immune response to the vaccine. If everyone, like you, delayed, their next dose of ocrelizumab we will end up with a major logistical problem catching-up with infusions after the vaccination programme is over. Most MS infusion units run smoothly because on average infusions are spread out over the year. A formal delay and vaccinate policy will result in major queues forming due to a backlog in infusions. This concertinaring effect will not go away and will then repeat itself every 6 months after that.

            If we made a formal delay-infusion COVID-19 vaccination recommendation, you could ask why have we not done this already for the annual influenza vaccine? And yes, if we do this in routine clinical practice we will potentially lose equipoise and have to do it for our trial patients as well and that will mean changing the trial protocols or delaying starting trials.

            I personally would rather everyone go ahead with their current dosing schedule and we then study people like you to see how your immune system, bot humoral and cellular, respond to the vaccine so that we can generate data that will allow us to make an evidence-based call on this issue in the future.

          • Prof G, I didn’t see your reply below before I answered lower down. I think, on balance, I’m awaiting being offered the vaccination and then I’ll take it when I’m offered and plan my next infusion accordingly 6 weeks after my 2nd jab. Just wish I knew when this would be so could plan.

          • “We have no published peer-reviewed data that states that by delaying your next dose of ocrelizumab 1, 2, 3, …… 6 months will make any difference in terms of your immune response…”

            The same argument applied when the pandemic hit, and yet we delayed treatment in many cases, with very little aggravation for patients. You know the underlying concepts better than I do.

            And infusions can obviously be staggered to mitigate the concertina effect. No need for people delaying their infusion for the vaccine to then come in for their ‘restart’ all in the same week, on the same day! This can be managed.

            I’m all in favour of producing controlled data as you suggest, but I suspect pwMS will vote with their feet (or wheels), and go for the best evidence available *now* – albeit circumstancial – than for evidence that may pay off for a future pandemic. It’s been a very scary and upsetting 10 months or so for many pwMS.

            The VELOCE study suggests mounting an immune response is blunted when vaccination is done early after B cell depletion. Why not study what happens when this is being done with 4-5 months (instead of 4 weeks) delay?

        • ProfK does that advice apply to all your ocrelizumab, ofatumumab or cladribine trial patients.? Does this mean the Chariot MS study is being delayed until all potential trial subjects are vaccinated? Or are you giving different advice to MS patients in trials or about to start trials?

          • We are discussing this issue across the board, and of course that includes pwMS entering trials since they are no different from other pwMS, except that they enrol in a trial. We need to wait and see how the roll out is going, and at what stage we arrive at priority level 4, which will cover pwMS. It *could* be by the end of Jan, which *could* mean a slight delay in trial recruitment. We will probably open ChariotMS from February, and expect a tardy start, but we’ll soon pick up as the pandemic clears; I’m optimistic about this.

          • It is common to have a different opinion when you don’t have data to support either the yes or the no. This is why evidence/data rules. In this type of situation, if there is no data, you can get a consensus by running a Delphi process to see how many MSologists agree or disagree with a statement. Typically, you set the bar at 75%, i.e. 3 out of 4 experts have to agree with a statement before you say there is a consensus. Maybe a Delphi process is needed amongst UK MSologists to answer this question.

            However, the real issue needs to be based on science. Is the issue simply delaying your next infusion until you have the vaccine? Or is it delaying the next infusion and the vaccine until you have some B-cell reconstitution? The latter could be defined as having 10 vs. 30 vs. 80 or higher B-cells/mm3 in your peripheral blood. I still have problems finding a consensus statement on what is a lower limit of normal in terms of peripheral blood B-cell levels.

            The point I am making is the questions the MS community are asking, about B-cell depletion levels and vaccine responses are fiendishly complex, there are simply no black-and-white answers. Another issue is timeliness; with the beginning-of-the-end of the COVID-19 pandemic beginning with the roll-out of vaccines globally means by the time we have answers to many of these question the COVID-19 juggernaut will have long past.

          • You are familiar with the term herding cats? Getting neurologists to agree is akin to herding recalcitrant, hormone-drenched, teenage cats!

  • Hi Prof G & Prof K & Mouse Doctor, thank you for all your updates. For patients on Ocrelizumab, can we take either the Astra Zeneka or Pfizer or is one potentially better for pt’s in our position vs the other from the data so far? I appreciate this could be opinion based but as a pt with MS, a Barts opinion from those who helped to get us treatment counts a huge amount 🙂

    • The Pfizer vaccine is on average more effective in reducing the risk of getting COVID-19 (95%). The AstraZenca vaccine will likely have a problem getting a license and was not as effective as the Pfizer vaccine; i.e. full-dose primer & full-dose booster was only 62% effective in preventing COVID-19 compared to the half-dose primer followed by full-dose booster, which was 90% effective. However, the latter dosing protocol was not pre-planned and happened as a result of an accident in the conduct of the study and hence the regulators are likely to request another study, before granting it a license. The next study is likely to take another 6 months. In addition, there are no older or higher risk people in the half-dose/full-dose cohort of the trial, which makes it even harder for regulators to assess its efficacy and safety across the population.

      In the UK politics may play a role and the AstraZeneca vaccine may be granted a provisional license on the condition that another study is carried out. However, based on the trial design and the results I think it will be highly unlikely that the MHRA will license the more effective dosing regimen (half-dose/full-dose).

      Although AstraZenca and the Oxford group are trying to put a positive spin on the fact that a mistake resulted in them finding a potentially more effective dose it is embarrassing and beggars belief that this actually happened.

      • Thanks Prof G, I’ll keep everything crossed I’m offered the Pfizer jab soon then. I’m CEV NHS staff so hoping to be prioritised although my Trust isn’t part of the initial 50 NHS Trusts. Following my neurologist appointment on Friday and my pre ocrelizumab chat with my MS nurse yesterday, I’ve emailed my MS nurse to ask that we consider pushing back my 5th Jan infusion in anticipation of getting the vaccination soon.

  • Thank you Prof G for your wise words. Ox-Az for me then 🙂
    Hope you’re taking care of you as well as pushing for your 5k goal xx

    • It is immunology 101 that if you have been previously had COVID-19 you will be immune and when you get vaccinated you will get more of an infusion reaction. In the Oxford vaccine there were a number of peole who were previously COVID-19 positive. It is argued that this does not influence outcomes, but it may be the odd one with a reaction is diluted by the many who do OK. Likewise, if you are allergic to latex, you may have an issue, as the plungers of syringes are made out of rubber, did the nurse ask. I had a vaccine recently and I dont think this issue was checked. We know infusion reactions are an issue so they should be expected, however we want to avoid anaphylactic responses. However, the staff are trained for this and can cope. I have witnessed this first hand after seeing someone conk-out after infusion of a drug, they

      • If they will allow it I’ll be there for my vaccine clutching my Epipens. I am hoping we will have a choice in the matter. I’ve been in anaphylactic shock a few times, I would rather risk that than covid for a few reasons.

  • A bit disappointing that many important points are not really taken into account here.
    The *absolute* risk reduction the vaccine achieves is under 1%, as mentioned e.g. in this comment from the BMJ.
    https://www.bmj.com/content/371/bmj.m4347/rr-4
    Also one of the BMJ’s editors brings up some valid points, but of course there are many more.
    Peter Doshi: Pfizer and Moderna’s “95% effective” vaccines—let’s be cautious and first see the full data
    https://blogs.bmj.com/bmj/2020/11/26/peter-doshi-pfizer-and-modernas-95-effective-vaccines-lets-be-cautious-and-first-see-the-full-data/

    • Maybe I’m a sucker, but I’ll respond: I’m not an MD but hold a doctorate in and was licensed to practice psych., so I am trained to listen more to what the client has to say, rather then rely on stats, which I also had to study (but not in overwhelming detail). Here, am I being led to consider the vaccines are insufficient? I can’t buy that, not because of my education, but because of my layman’s understanding. 95% efficacy means to me, that over the course of two or three months (and hopefully longer), I have a 95% chance of not contracting the virus when I am exposed 15 minutes to a group of maskless idiots. That appears to be much better than in some reported situations where upwards of 50% of people (and probably more), seem to get it easily in the right situation. This “right situation ” where I live, is compounded by the many who refuse to take precautions, seemingly following their fearless leader (you know who). Now, by reading this post, I am asked instead to believe that my chances of actually contracting the virus without vaccine are something less than 1%. I believe this is non-sense. I know there is some very fancy statistical thinking going on to support that conclusion, and the web site the stats are referenced from appears on face to be quite legitimate, I still don’t buy it.

      I think you have to look at the group of subjects in the study, to begin with. Someone who volunteers, may be more likely to follow good health habits and avoid risky situations, lowering their overall risk. Compare this also, with the non-maskers hanging out with one another in various high risk situations. Where do you think the virus will congregate? With these people, of course. I’d like to see the data from third world countries, perhaps this would provide insight. What would the data look like if we only enrolled “night club people”?

      Whatever the statistical considerations, I do know that hospitals are reaching their max capacity, and we haven’t even concluded the Thanksgiving and realized the Christmas, surges yet. Many more people are dying as a result of the virus. That number doesn’t lie and can’t be played with. And yes, I am higher risk, but so are a lot of others- perhaps 1/3 of the population (?). So, I don’t want to be stuck in the hospital hallway with others deciding my fate based on their lack of resources and my premorbidities versus someone else’s premorbidities. That’s clearly (to me) the way it will go without a vaccine, and it appears we have no time to wait. So I’ll take a chance with the vaccine. Non-live vaccines have worked for me in the past (I have MS), and I remember what happened with my MS when I got the flu last time (before I started taking flu shots).

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