A presentation at AAN2019, seemingly attempts to discredit the view that we suggested that neutralizing antibodies can be important for some people with MS who are taking alemtuzumab. So you asked have I seen it?
Antidrug Antibodies Have Minimal Impact on the Pharmacodynamic Profile and Clinical Efficacy of Alemtuzumab in RRMS Patients From the CARE-MS Studies Tjalf Ziemssen , Antonio Bertolotto , Samuel F Hunter , Jan Lycke , Alan Jacobs , Luke Chung , Qifeng Yu , Isabel Firmino , Christopher LaGanke
However it is been presented in support to the approval of people being allowed to use dose 3 or more in treatment failers. But of course I haven’t seen it….I’m not at the meeting but I guess it is similar to the poster presented at ECTRIMS 2018 by only Jacobs A, Chung L , Yu Q , Firmino I which did not seem to have the extra academics. I will get to see it as we have Spies (Neuros) at the meeting and the code means we can get it whilst the link is active.
The poster at ETRIMS 2018 reports on anti-drug antibodies and says they make no effect. Sure I buy and know this at the population level. This was presented much earlier by the Cambridge group.
However the ADA are made up of binding antibodies and neutralizing antibodies. Binding antibody levels are about 90% more common than neutralizing antibodies. So we need to askwhat happens when you only look at neutralizing antibodies. In the CARE-MS trials 75% of people had binding ADA but only about 30% had the neutralizing antibodies that could stop the drug working. Those with low levels (Titres) of neutralizing antibody levels still deplete, we know and accept this. So is it surprising that ADA do not impact on the clinical course. Not really
What happens to the individuals?. This is the information that I have asked about over and over again. Some people will not respond the question is how many?
The neutralizing antibodies were invisible from Google searches as they were called “inhibitory antibodies” in the regulatory documents, rather than neutralizing antibodies. I stumbled across them because the document containing the inhibitory antibodies in MS on page XXX had neutralizing antibodies in relation to a monkey experiment on page YY.
That set off my conpiracy theory.
I suspect that the dosing schedule of alemtuzumab was actually generted to limit the effect of ADA, Cambridge even did studies to get rid of them, you wouldn’t do that if they were not an issue. But they were never mentioned during the commercial development. The irony is that alemtuzumab was the worlds first antibody designed to get rid of ADA, when its biology makes it probably the worse antibody for generating ADA, because I think it blocks tolerance and so all the immune system sees when it is being infused is alemtuzumab and over 60% of people make ADA in the first month when there are essentially no lymphocytes at least in the circulation.
This makes you ask is being hidden?
In the past, in the haste to show that you can go onto fingolimod if alemtuzumab fails they pinged out a a poster at the European Neurolgy meeeting in 2015, but forgot to look at the actual response and perhaps the reason why the person was switched to fingolimod, as they were perhaps too focused on fingolimod. They (Selmaj et al.2015) showed that 2 out of 6 people did not deplete on the third cycle of alemtuzumab. One imagines this may contribute to the idea to switch to fingolimod.
Of course we know that most people respond to alemtuzumab, we don’t need to see the poster we can read the work from Cambridge. The question is how many don’t?
If you dig you find dirt, mole hills contain dirt , this subtifuge allows one to make a mountain, well at least three papers, of it.