Dr. Fluge presented a detailed review of the RituxME trial at the IIME Research Conference on May 31, 2019:
Came across Dr. Fluge answering "interesting" audience questions [end of the Tronstad video about 20:20]
@Gemini I just watched the full presentation of Dr. Fluge's review of the RituxME trial and also his audience questions at the end of the Tronstad video. Thank you again for tagging me. These are my thoughts and I would LOVE it if some day, someone can explain to me where I am wrong b/c I see several flaws in the trial.
He explicitly said that the Rituximab doses for the final Phase 3 trial were NOT the same doses as the Open Label trial which had many long-term responders. If you change the BSA (body surface area) formula dosing, which is specialized for each patient, to a standard dose of 500 mg per patient, it is NOT the same thing. My own Ritux dose (using the BSA formula) is 600 mg per infusion which means that 500 mg would not be a strong enough dose for me. The only reason I can think of for the change in dosing is the cost of the medication. I cannot think of a single clinical reason for the change.
Dr. Fluge replied to an audience question that the positive results of the Phase 2 open label trial will be something that he wonders about for the rest of his life. I wish I could ask him WHY the change in dosing between those two trials is not considered a major factor? There is no question in my mind that in the final Phase 3 trial (for doses 3, 4, 5, and 6) that 500 mg per infusion simply was not a high enough dose for many of the subjects. In addition, it was a change in protocol which makes it an inconsistent or confounding variable in my opinion.
I also saw many other problems. When he said that some of the reactions (both positive and adverse) were short-lived, there is no question in my mind that some of the subjects were responding to the incredibly high dose of Dexamethasone. 8 mg is an extremely high dose that literally sent me to the ER with uncontrollable tachycardia and other adverse events (in my case this was a full year before I ever started Rituximab).
Dr. Fluge also said that 40% of the subjects had "allergies". I realize this does not mean "MCAS", but I suspect it is highly likely that many of them did have MCAS and that the Dex temporarily brought relief (and in others it triggered very adverse effects like agitation, tachycardia, insomnia, steroid induced psychosis, etc).
In addition, he did not state the infusion speed (unless I missed it which is possible). When I get Rituximab, in addition to having ZERO steroids, I get an unbelievably slow infusion speed to reduce the chance of any allergic reactions or any infusion related reactions (and I have never had any). I also get no extra fluids and my pre-meds are IV Benadryl, (oral) Tylenol (Acetaminophen), and (oral) Pepcid (Famotadine).
These are the pre-meds that happen to work the best in my own personal case but every person is unique and different so it is possible that some subjects reacted to the pre-meds that they were given (especially to the Dexamethasone). I also believe that some subjects reacted to the Albumin (and I have never heard of giving Albumin with Rituximab but maybe this is more common in Europe vs. in the US)?
I also have thoughts re: the selection criteria and outcome measures but those are less concerning to me b/c none of that even matters with the discrepancy in dosing between the Phase 2 Open Label Study and the Phase 3 RituxME Trial. I truly wish that there was someone who could explain this to me re: the dosing issue!