#ECTRIMS2021: Cladribine and COVID-19

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How safe is cladribine during COVID-19?

I have been saying that based on its mode of action cladribine works as a semi-selective B-cell depleting agent similar to an anti-CD20 or anti-CD19 therapy. However, cladribine has an advantage as it is used as an IRT (immune reconstitution therapy) so is not associated with continuous immunosuppression. Cladribine is also CNS penetrant and hence targets CNS resident B-cells.

Another advantage of cladribine is that as it kills B-cells in the periphery new migrant naive cells are emerging from the bone marrow. Hence peripheral B-cell counts don’t drop to zero, which explains why pwMS treated with cladribine are vaccine ready and make good antibody and T-cell responses to the COVID-19 vaccines. Importantly, the latter seems to be independent of where in the cladribine treatment cycle vaccinations occur and appears to be independent of peripheral lymphocyte counts. 

The following is the safety data I presented and ECTRIMS in relation to pwMS treated with cladribine who had COVID-19. Importantly, out of 503 cladribine-treated pwMS, there were only 3 fatalities (0.6%). This is an order of magnitude lower than that recently reported with ocrelizumab (Hughes et al. Mult Scler Relat Disord. 2021 Apr;49:102725.).

The list of other adverse events is self-explanatory. 

Overall of the high-efficacy B-cell depleting DMTs, cladribine is emerging as the one DMT that seems to be the best tolerated with a low risk of severe COVID-19 and at the same time allowing to receive COVID-19 vaccinations with confidence. The fundamental difference is that cladribine is an IRT and many HCPs and pwMS don’t feel comfortable with the fact that after an IRT you have to play a wait-and-see game, i.e. no treatment until MS disease activity returns. If you are one of these people you need to ask yourself if you are not prepared to have an IRT could you please ask yourself how are we the MS community going to ever find a cure for MS? 


Please note that I am the principal investigator on the oral cladribine phase 3 programme and have been involved with its development since 2002. I am therefore heavily conflicted so you may want to interpret anything I say that is positive about cladribine with caution. 

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General Disclaimer: Please note that the opinions expressed here are those of Professor Giovannoni and do not necessarily reflect the positions of the Barts and The London School of Medicine and Dentistry nor Barts Health NHS Trust and are not meant to be interpreted as personal clinical advice.