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.
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!