Good news for cladribine, not so good for ocrelizumab and fingolimod
Data has surfaced today at an International MS meeting on the impact of MS disease modifying treatments and it looks like it is supporting the biology. As presented by Dr Anat Archirion from Israel and as anticipated from past vaccination data, there was a poor (less than 20%) seroconversion (assessed using the Eurimmune Ig assay) with ocrelizumab and fingolimod, but cladribine showed good seroconversion. Information about other agents were not yet reported. The information was based on a sample of about 30-40 people and remember based on data that has emerged from the cancer field, people can make a T cell response despite, an inhibited B cell response. It remains to be seen whether this will happen in MS and also whether vaccinated individuals become infected. However, obviously this is a possibility. The result is consistent with the B cell hypothesis that we published some time ago. This needs to be confirmed, but as it is following what was predicted, it is likely this will be more or less confirmed. This will happen within the next month or so I suspect.
However we have a different message coming from Sweden and sad to say this glass half-full message comes a bit late as the glass half-empty message above tends to make the take home message appear abit SH1. Hopefully the referees don’t read the blog or twitter, as it is under review. This looks at people who got infected with SARS-CoV-2 and makes the case that people make an antibody and T cell response and the response to vaccines will be great. But looking at that picture on twitter either rituximab is a lot less effective than ocrelizumab or the authors are in for a big shock. Indeed if you read the paper it is not as fluffy and lovely as you think.
So what does it say….First thing it suggests is that you are talking rituximab it may increases your risk of developing symptomatic COVID-19…This data was reported last summer on iWMS and profG did the stats and is some of the better data on this. They say in the study 89% of people had symptomatic covid by only 19% were seropositive. This is poor seroconversion as other people are showing. The difference here is that they argue that people with MS show poor seroconversion. However, that is not supported by the data in the story above. Next up, they say there is a T cell reponse and indeed there is a T cell response in some people especially if you seroconvert. but if you are sero(antibody negative) there is not much of a T cell response. Now read the abstract and that says that the idea that rituximab inhibits T cells by blocking antigen presentation is probably rubbish because here they would argue that antigen presentation isn;t blocked and you get a T cell response, but the actual data is not so clear cut in my mind.
This gives a bench mark about what baseline T and B cell responses look like, let’s see how they change after vaccination. I wonder if Sweden are using the Astrazeneca vaccine after all the Astra is Swedish.
Development of Humoral and Cellular Immunological Memory Against SARS-CoV-2 Despite B-Cell Depleting Treatment in Multiple Sclerosis. Cell Reports Medicine
B-cell depleting therapies are widely used as immunomodulating agents for autoimmune diseases such as multiple sclerosis. The possible impact of B-cell depletion on development of humoral and cellular immunity to viruses and specifically SARS-CoV-2 has raised concerns with the COVID-19 pandemic. We here determined humoral and cellular responses in participants of an observational trial comprising several multiple sclerosis disease modulatory drugs (COMBAT-MS; NCT03193866). Patients on B-cell depleting treatment, who previously had COVID-19-like symptoms, developed anti-SARS-CoV-2 antibodies and/or T-cell memory irrespective of their B-cell depletion status. Furthermore, antibody titres were similar to those observed with other treatments or controls, and anti-SARS-CoV-2 T-cells displayed functional similarity to controls producing IFN-γ and TNF. These results inform on the role of B- and T-cells in SARS-CoV-2 immunity and provide evidence that B-cell depleting therapy does not substantially abrogate SARS-CoV-2 immunological memory, in turn suggesting a low risk for reinfection and potentially responsiveness to vaccination.
This suggests great, the reality is not so great…..They have done so much work but too slow to publish, if it doesn’t get accepted now it will be time to rip it up and start again. Maybe if I had written it, it would have been more doom and gloom and the authors would not have to do a major, re-write as it looks like time to eat some humble pie or is this Kladdkaka.