Saturday, 3 March 2018

Blast from the past: something the new readers don't know

You asked does Ocrelizumab need to be dosed so often?

I repost this from last year about the 4 year old data and ask why it has not been published?

We need a study to address the question, is there induction therapy potential. 


We have published CLICK HERE  a paper which suggests that B memory cells are a major target for therapy and suggests that ocrelizumab may work like alemtuzumab, and so this suggests that CD20-B cell depletion may have induction therapy (immune reconstitution therapy) potential.

Highlights: 

  • Ocrelizumab has induction-therapy-like characteristics
  • 6 monthly dosing could be too often for some people

This is supported by data that Pharma hold and this is the shocking revelation of the paper.

Why shocking? This is because many/most neurologists will not be aware of this data and its implications.

I have asked a few and indeed they didn't know about this! 

Did you?

The data was presented as a poster at ECTRIMS in 2012 and again at the ANN 2013 (see below) 


It is shocking that many senior authors have helped pharma dump the information in meetings abstracts, never to surface in the science literature.

Indeed, it has been over 4 years since the data was presented and so there has been ample time for a paper to surface, had the company wanted it, and had the presenting authors done the right thing.

(Yes ProfG is guilty of the above as he is on many pharma posters that have yet to surface in the literature. Two wrongs do not make a right)

Someone, from the blog sent details (thanks for that) of  the original poster. Here is the QR code
The inference is clear, very, very clear and this is that.... ocrelizumab is an induction therapy or IRT, or at least a therapy with long-term efficacy, which may not need to be dosed every six months.

Here is the data presented (Figure 4)



On a population level many people were still doing very well 18 months after the last dose. 

This type of response has also been seen with Rituximab in other studies. Maybe the Neuros in Sweden can trawl through their registry to see if they can come up with any data as they have a lot of people taking rituximab.

Therefore, it suggests that 6 monthly dosing may be too often, at least for some people?

This is important because Ocrelizumab use is not risk free.

Development of ocrelizumab in arthritis and lupus was terminated because of very serious infections and this caused a number of deaths.

By persistently depleting your B cells (and some T cells) you have a persistent risk of infections. These will occur once ocreliziumab becomes licensed. Therefore, it is important that use of ocrelizumab should be de-risked if possible.

The dosing regime is based on a 6 months dosing period because CD19+ B cells are depleted for 6 months. This keeps all CD20+  B cells under control.

However, if you accept that memory B cells are important targets, they are depleted in some studies for over 24 months in some people, in other people for 5 years. 

So 6 monthly dosing could be too much?

Can you use memory B cell numbers as a way to determine retreatment? They have in other diseases.

__________________________________________________________________________
                            Total Memory B cells                 Class switched memory B cells
__________________________________________________________________________
Healthy Control      30.5 ± 6.9%; P = 0.001           18.3 ± 5.8%  P = 0.001
Responder             6.3 ± 0.9%                             3.6 ±   0.5%                      (5 year)
Non-Responder      51.1 ± 23.2%  P = 0.009          42.8 ± 18.1%  P = 0.036;     (3-5 year)
__________________________________________________________________________

Amolik JH et al. Athritis rheum 2007; 56:3044

Given the risks of ocrelizumab, surely a trial should be performed to determine whether ocrelizimab is indeed a (PIRT) Induction Therapy to make it safer for pwMS.


Maybe there is a good reason for frequent dosing in MS.

CoI None. 

3 comments:

  1. Maybe neurologists don't know it -even if neurologists know it all from nature- but rheumatologists -and probably oncologists- are pretty aware of this mechanism. Nothing groundbreaking here.
    This is another plus of Rituxan over Ocrevus, that you can easily adjust not only the frequency but the dosing too. In fact many old Rituxan patients get their infusion once a year. Even some Ocrevus neurologists have started to monitor B cells before redosing. I have even seen proposed to have a therapy break at 2 years to prevent chronic neutropenia.
    However, this "induction" doesn't seem to offer any added benefits to this therapy (since you compare it to Alem.).

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  2. Good to see rheumatologists are enlightened

    ReplyDelete

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