Tuesday, 11 July 2017

Third Dose Thoughts..Time for Information in the public domain

Yesterday I spoke on the issues of using antibodies and it is evident that some people have genetic backgrounds that limit antibody function and importantly that neutralizing antibodies develop. 

If neutralizing antibodies develop antibodies can stop working. This is true of any protein drug.

ProfG's post this morning me reminded me of something a neurologist told me yesterday about their experience with multiple cycles of alemtuzumab, where they felt the treatment stopped working.

I started asking questions in November last year and have been fobbed off a number of times. I'm not a mouse but a ......ferret. My jaws lock when I find a problem. 





Based on the work presented at ECTRIMS 2016 of the CARE-MS extension studies and the experience of the Cambridge group about 50% of people treated with alemtuzumab require a third course.

Tuohy et al. 2015
"Over a median 7-year follow-up (range 33-144 months), most patients (52%) required just two cycles of alemtuzumab. In the remaining patients, relapses triggered re-treatment to a total of three cycles (36%), four cycles (8%) or five cycles (1%)".

This experience was replicated with the Cardiff group

Willis et al. 2016
"Forty patients" (of a 100) "were retreated with at least one further treatment cycle."

So the extra cycle means that MS goes away in 88% of pwMS. So the extra cycle must we worth the investment of an extra ~£21,000 to save, wasting ~£58,000?


Now the Ferret says remember that we recently reported.Based on the phase III data. 

Nearly 80% of people treated with alemtuzumab make "inhibitory antibodies".  

Google translate of "Pharma" into "English" translates this to mean "80% of people treated with alemtuzumab make "Neutralizing antibodies".

Importantly the public domain data reports that about 30% (n=239/764) of people have neutralizing antibodies at 12 months after the second cycle. 



Is this important? 

If we look at year 1, there were only 5/789 (0.6%) who had pre-existing antibodies. 

Were these important?. For the population..No but for the individual..maybe

In CARE-MS 1, 1/3 people had high titre neutralizing antibodies at 12 months and they depleted to 1.8 x 10*9/L lymphocytes (This is not good depletion..possibly no-depletion.

How many people of the 239 people with neutralizing antibodies at year 3 got a third course and how many of those people did not deplete or did not deplete well? 

What was their pre-existing titre?

Is it important?

Should we be screening people's blood before doing a third injection. See below 2/6 people getting three courses don't deplete well.
Surely it can't be a third of people having issues, but without the data to say otherwise, what should we think? 

The ferret is on the case and knows where to get an answer. 

So if we are thinking of third cycles, which surely we should be doing, perhaps we need abit more data, put into the public domain. 

Maybe it has been done for ECTRIMS 2017 already in response to my request, and if not there is still time for the late breaking session! 

This may help NHS make the sensible decision to allow the third injection, whilst de-risking the process for perhaps a few individuals

CpoI: None relevant

4 comments:

  1. Good job
    "80% of people treated with alemtuzumab make "Neutralizing antibodies".
    Looking at the graphs looks like Fingolimod is the "Fire department"
    Why them not allow the "Fire department" take a hold after the second round of Alemtuzumab?
    One sould make the case "is not theirs brains that are burning"
    Thanks
    Luis

    ReplyDelete
    Replies
    1. I agree it says fingolimod is emptying the blood and hopefully the people did well. This is why it is important to have alternatives because some people have genes that mean that IgG1 do not do their job properly.

      Delete
  2. Do you have any experience of breakthrough of disease activity in patients during 1st year of alemtumab treatment before the 2nd cycle?

    ReplyDelete
    Replies
    1. This can occur no treatment is 100percent effective.

      Delete

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