#MSCOVID19: ABN Guidance Update

Barts-MS rose-tinted-odometer: ★★★

The ABN have updated their COVID-19 guidelines, which are beginning to move towards the evidence. However, the guidance on cladribine is not supported by the evidence nor the science, i.e. how cladribine actually works and its impacts the immune system.

The latest guidance states “the risk of severe COVID-10 disease is increased for many months after ocrelizumab and cladribine”. I am not sure there is evidence to support the statement about cladribine. Ocrelizumab and other anti-CD20 therapies are given continuously and hence the risk does not go away. However, cladribine is an immune reconstitution therapy and is reversible. Even in the depletion phase of treatment, the level of immunodepletion is modest, particularly for CD8+ T cells (see slide show below) and innate immunity is left intact. In our opinion, this pattern of immunodepletion is not sufficient to pose a risk to people with MS treated with cladribine and is supported by the emerging pharmacovigilance data.

The good news is that the guidelines state that for both ocrelizumab and cladribine “self-isolation for all that time is not appropriate except for individuals with multiple other risk factors”, which is compatible with our practice.

I am also reassured that their guidance has also softened for alemtuzumab; i.e. “we would anticipate pwMS being advised to strictly self-isolate for at least four weeks after an alemtuzumab administration”. This has been our practice since we started dosing alemtuzumab again. The rationale for the 4 week time period I assume is based on the impact of alemtuzumab on innate immunity and is supported by trial data; i.e. the viral infection risk falls rapidly after four weeks, presumably because monocyte counts recover.

The ABN is also recommending two weeks of self-isolation after high-dose steroids, which is pragmatic advice based on the risk of severe COVID-19 identified in the Italian registry studies.

The new guidance has also made a comment about vaccine readiness; “patients contemplating ocrelizumab should be advised that they may not be able to receive a future SARS CoV2 vaccine if it is a live vaccine, and they may not respond immunologically to a dead or inactivated vaccine. Consideration should be given to delaying ocrelizumab re-treatment”. It is interesting that none of the other DMTs is specifically mentioned when it comes to vaccine readiness. I am sure live viral vaccines will also be contraindicated in patients on S1P modulators (fingolimod and siponimod) and on some of the other immunosuppressive DMTs such as natalizumab and possibly even teriflunomide based on their current SmPCs.

The interesting thing about vaccine readiness is we don’t know about how important T-cell responses are in relation to these emerging vaccines and whether or not people on anti-CD20 therapies will mount an adequate protective T-cell response to the SARS-CoV-2 spike protein and other antigens. Everyone focuses on antibody responses when they may not be that important in protective anti-SARS-CoV-2 immunity.

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.

CoI: multiple

Twitter: @gavinGiovannoni Medium: @gavin_24211

3 thoughts on “#MSCOVID19: ABN Guidance Update”

  1. What is the general advice for people with MS regarding live and non-live vaccine if they are not on DMT?

  2. It’s a real kick in the teeth when you are vulnerable to covid because of a treatment, then the very same treatment means you can’t have the vaccine despite being exactly the sort of person it is designed for!

    Is there a ‘non live’ vaccine coming along behind it? I know there are some in the pipeline but are there actually likely to be any that we can have in the not so distant future?

    How long of a break from anti CD20 would give us a vaccine chance?

    1. 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.

      Is there a non live…yes

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