Don’t “Boris” your treatment!

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Many of you have been caught by surprise by the Prime Minister’s latest announcement: London and Southern England moved into the unexplored Tier 4, and no ‘Jingle Mingle’ of households on Christmas. This last-minute and – honestly profane – cancellation of Christmas plans has been a hard nut to crack for many of us. So much the more the prospect of a vaccine is the equivalent of Bethlehem’s star, in which many of us find motivation to put up with the latest restrictions on the path to a new post-COVID-19 Testament. 

Star.png
https://www.almanac.com/star-bethlehem

Although I entirely understand the importance of this outlook and totally agree that getting the vaccine is not only a personal reassurance but also an act of citizenship, I would like to ask you as a pwMS to give sufficient consideration to the arguments below before you cancel any ongoing treatment plan. It is important to realise that the COVID-19 vaccine and your MS treatment are mutually compatible and that you are putting yourself at risk of (unnecessary) disability accrual by halting or delaying your treatment. 

It is indeed true that vaccine responses are most likely blunted in pwMS when treated with ocrelizumab or fingolimod as well as when pwMS still have incomplete immune reconstitution after treatment with cladribine or alemtuzumab. Stopping or delaying the next treatment course might (but importantly not necessarily) translate into an enhanced vaccine readiness when immune cells that are depressed under treatment repopulate. However, …

First, by delaying your next treatment course when the COVID-19 vaccine becomes available and subsequently wait for B cells to replete and thus to reach the lower level of normal (ocrelizumab – 72 weeks after the last infusion, cladribine – 30 weeks after the last cycle, alemtuzumab – 30 weeks after the last cycle, fingolimod – 8 weeks after the last intake), you will be delaying having the vaccine to a time point when the peak of the pandemic will potentially be over. It is now that London (and soon the whole UK) has gone into Tier 4 and now that we are seeing the biggest surge in cases ever. A blunted vaccine response is still likely to represent meaningful protection against COVID-19 in the following months than no vaccine at all. Therefore it would be most useful for pwMS to have the vaccine as soon as – logistically – possible.

Second, by stopping your MS treatment you put yourself at risk of returning to your baseline pre-treatment disease activity level. And by stopping certain MS treatments, in particular natalizumab and fingolimod, you put yourself at risk of rebound MS disease activity on top of this baseline pre-treatment disease activity. For fingolimod, the reported severe relapse rates range from about 10% to 25% ± 4 months after stopping treatment. In a study of 27 people with severe MS (which are the people that are in general put on natalizumab) within 6 months after discontinuing natalizumab, 18 patients experienced clinical relapse and 3 additional patients had radiological activity without clinical relapse. Let the numbers speak for itself!

Third, by delaying the next course of ocrelizumab, alemtuzumab or cladribine you make it impossible for neurologists to give you evidence-based advice on the treatment strategy in your best interests. The phase III clinical trials to prove Ocrelizumab’s efficacy have all been done with ocrelizumab being infused every 6 months. Although there is evidence that ocrelizumab may work beyond this time interval, we do not know how long the treatment effect lasts and we certainly cannot quantify it. There are no reliable biomarkers available to guide clinical practice. Some people have suggested to use the extent of B cell repletion as an indicator for retreatment. However, relapses have been reported in pwMS post-CD20 depletion that still had very low B cell levels. There might be some promise in determining B cell subsets (such as the memory B cells) as a biomarker for retreatment. However, this theory also remains unproven. Hence, any advice on how long you can reasonably delay your next ocrelizumab infusion is essentially an expert opinion with no guarantees. And even if clinical or MRI relapses would still be suppressed for a significant amount of time after the last infusion, we certainly do not know how these treatment holidays affect the treatment effect on brain volume loss etc. In addition, it significantly complicates the interpretation of your MRI monitoring. What if a new lesion appears on your follow-up MRI after you had an 11-month interval between two ocrelizumab infusions? Does this mean there is disease breakthrough and thus that you need to switch gear treatment-wise? Or is it due to the lengthening of the treatment interval? I honestly do not know the answer to this, and nor does the MS community. I do know that the extension of the dosing interval of commonly used MS treatments will cause delay in assessing whether a treatment is the right fit for an individual’s MS and thus whether it can effectively halt ongoing inflammation. The same rationale applies to delaying the second course of cladribine and alemtuzumab. 

In summary, I feel the best chance for pwMS to be protected against the looming threat of MS disease activity and the COVID-19 virus is to go ahead with their disease-modifying treatment and have the vaccine as soon as it becomes available. The more pwMS vaccinated, the merrier! 

About the author

Ide Smets

16 comments

  • Thank you this. I’m due my next ocrelizumab on 5th Jan and have been told that any vaccination must be either 6 weeks before or after. There was a chance I might get it this month as NHS but that’s looking unlikely now. If that had happened, I would have moved my infusion back the required 6 weeks from the 2nd injection. Once I’ve had my treatment I plan to wait at least 6 weeks as advised but I’ll have to see when it’s offered and may prefer to wait until nearer my next infusion.

    I think the issue here is all the conflicting advice from neurologists that are being reported by pwMS on social media. It appears that there are neurologists advising people on ocrelizumab not to have the vaccine.

    • Hi Debbie! I agree there are many different opinions around what makes things very confusing for pwMS. The 6 week interval seems reasonable and is a good bargain between vaccine readiness and staying on treatment. Personally, I would never recommend not having the vaccine.

      • I did consider pushing back my Jan infusion but decided to just go with the flow re the vaccine. If I was offered it this month I’d take it and then push infusion back but not push it back until had date for vaccination. As it is, I’ve not been offered it so planning infusion on 5th and then wait and see. Can’t say I’m not nervous either way though.

  • Unfortunately my MS centre have already altered the regime for Ocrevus and only administer the next dose when CD19 levels start to come back up. Reading this post had made me slightly worried that they are doing this without the evidence to back it up and are putting my health at risk

      • For the record, I wanted to add: I am not really worried about postponing ocrelizumab for one, two or three months. That will most likely not make a difference in terms of efficacy but on the other hand will unfortunately also not be sufficient for the majority of the people on ocrelizumab to replete their CD19 counts and thus have a better response to the vaccine. When you go beyond these short reinfusion delays, there is just no good guidewire to decide when to retreat and this creates problems in terms of disease monitoring without any guarantee of a good/better vaccine response.

  • Hi Dr Smets,

    Thank you for your post and I was especially interested your thoughts and findings regarding Ocrelizumab. I went ahead with my full infusion on the 16th December, with a view that I would have the vaccine (after understanding if it would be okay) – 6 weeks from the 16th. I was happy to go ahead and I’m really grateful that my Neuro team were organised and looked after well.

    I haven’t heard where I am on the list as I have other health issues and it might or might not put me in extremely vulnerable category but I wait patiently for my GP surgery to make contact! I’m extremely delighted to say my two elderly neighbours (in their early 80s) have had the vaccine last night and all is well 🙂

    It is concerning that other MS Neurological teams are acting on different instructions. Could we not see someone advising them that we all do the same! To save, worry, stress and confusion. I forget sometimes how much stress is involved with having an infusion but you’re always better off afterwards, as you’ve seen your healthcare team, updated on any issues and you feel valued as a patient that they are working with you to quash this disease from getting worse. Obviously, the less MS smouldering away – the better you will be able to stave off COVID-19 and or get through it too!

    It seems odd to say this as the festive season isn’t that great at the moment – but I hope you all have a lovely break and at least get some time to unwind and put your feet up with a glass of something too!

    All the best and Happy Christmas and New Year xxx

  • I’ve just had my covid vaccine, they had a spare one where I work at the NHS hospital. I had Lemtrada two years ago.

  • Hi! Thanks for sharing such important info!👍🏼
    I’m not on DMT at the moment, diagnosed end of Feb this year and than COVID-19 came.. Anyway since I’m worsening (even numbness in my mouth/tongue lately…) probably Ocreluzimab or Natalizumab is the best to start. What should I do, I live in Holland where they haven’t even started vaccinating?! Hope to hear, Thnx!

    • My advice would be to give your MS priority, and start treatment as soon as possible. Choices for a DMT are determined by many more factors than vaccine readiness alone, so please do not only look at treatment choice from this perspective. Anyhow from a vaccine point of view, I would recommend natalizumab as you would be able to mount normal antibody levels after vaccination.

      • Yes I understand MS has priority and of course we make the desicion (finally.. and hopefully soon) for which DMT not based on the vaccin. I have more questions and stuff to read about that also! For now many Thanks for such a quick reply, very helpful and something to discuss also with my doctor. All best wishes!!🙏🏼🌸

  • Insightful post.

    What’s the rationale for the 6 week window pre and post infusion some have mentioned. Seems rather arbitrary to me….

    • As far as I know, the official recommendation is to leave a 4 week gap between vaccine and DMT treatment. This is definitely arbitrary but on the other hand the immune system needs some time to develop targeted antibodies to the vaccine antigens, and if you wipe out the immune cells with ocrelizumab too early you might undo this process. In my opinion, a two week interval between DMT and vaccine would be the absolute minimum.

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