Avasarala J. Anti-CD20 Cell Therapies in Multiple Sclerosis-A Fixed Dosing Schedule for Ocrelizumab is Overkill. Drug Target Insights. 2017 Oct 25;11:1177392817737515.
Anti-CD 20 therapies have found significant uses in multiple sclerosis (MS). Based singularly on the accumulated evidence with the use of rituximab (RTX; Rituxan, Genentech, and Biogen) in neuroimmunological diseases, ocrelizumab (OCR; Ocrevus, Genentech) was developed as a treatment option for MS and selectively targets CD20 B cells, a cell surface antigen found on pre-B cells, mature, and memory B cells, but not on lymphoid stem cells and plasma cells. On the basis of indirect evidence, elimination of the antigen-presenting capabilities and antigen nonspecific immune functions of B cells appear to be central to the therapeutic efficacy of anti-CD20 B-cell therapies. An important question is this-Why does the drug need to be dosed at fixed intervals and not based on a measurable endpoint, such as tracking peripheral CD20 cell counts? There is minimal scientific validity in infusing the drug every 6 months particularly if CD20 cell counts are negligible in the peripheral blood. In this analysis, a case is made for following CD19 cell populations as a surrogate for CD20 cells on a monthly basis to guide OCR redosing parameters and does not follow a scheduled dosing parameter.
Memory B Cells are Major Targets for Effective Immunotherapy in Relapsing Multiple Sclerosis. https://www.ncbi.nlm.nih.gov/ pubmed/28161400
So should you dose every 6 months?
I suspect Pharma and Neuros will have their fingers in their ears going La, La, La, La, La in the response to the idea of personalised medicine…I could be wrong
They will give the drug every 6 months and they will follow the label.
This is what the data from the trials indicates them to do and that is the label.
However, if we have a death (based on events in Lupus and Arthritis where termination of drug development occurred) because of severe infection due to cell depletion, I suspect that people will “pull their fingers out” and take notice of the views above and below.
There will of course be deaths in people taking drug, because this happens as part of life and not all deaths are drug related. Adverse events could occur early or late (We are aware of some rumors) this will be due to chance of when the infections strike and there will be infections associated with B cell depletion. But if you take the treatment forever the risks must accumulate due to chance
However, I have hypothesised that ocrelizumab is an induction therapy just like alemtuzumab and cladribine…..Why?
Because, in my current view (this could change) they work the same way and all deplete memory B cells
Based on the unpublished, (why was it not published…Is it ethical to put people through these trials and not properly document the data but in the public domain see the Stephen Hauser ECTRIMS talk or [Click here]), ocrelizumab phase II extension data set show activity in most people 18 months after the last dose.
Does it need a tragedy, before people think about this?
Maybe the manufacturers should plan and do a trial now…Maybe I am wrong and they can shut me up!
They can do this by showing us the data.
Personalising Treatment is surely a positive move.
COI: Non-relevant yet.
complement fixation to blow holes in the target and uses antibody dependent
cellular cytotoxicity to blow holes in the target.
complement binding site on the antibody molecule stimulates the complement cascade starting with C1 and ending with C9.