The first thing you want to know is improvement in the condition but for ME/CFS the measures are so subjective and placebo and relate issues so big that you are not going to get any direct data. There are not going to be any indirect or surrogate data because there are no abnormalities like raised CRP that we know to be surrogates. There are no known relevant autoantibodies so they tell us nothing. So there will be no efficacy data of any use.
I do not see any particular scientific rationale for this particular drug either, so even if the patient is purely being used to generate pharmacodynamic data I don't see that anyone would know how to interpret it.
But the Fluge/Mella pilot study - not Placebo controlled - does seem to have generated enough data to warrant the new phase II RCT, doesn't it? How would this be fundamentally different here, in the most ideal case?
Adverse effects to drugs are often dose-independent, especially if they are hypersensitivity phenomena. The dose makes no difference.
Ah right, I was rather thinking about potential pharmacodynamic mechanisms (like some unknown off-target effects that shouldn't be there) rather than anaphylaxis/hypersensitivity.
If I understand correctly, CRS and ICANS (SAEs of teclistamab) would not be hypersensitivity, would they? If not, would these be expected to be dose-dependent SAEs?
It depends on the competence of the physician. In the hands of a very careful physician serious ADAs like sterile pneumonitis may occur in perhaps 5-10% of cases. Fatal ADAs might be as low as 0.2% but may be closer to 1% in real life cohorts. In the hands of a physician who does not know what they are doing the risk is higher. There were a lot of infective deaths from rituximab when people started using it without knowing what they were doing.
I think I'm misunderstanding something here - aren't ADAs against the drug, rendering it ineffective? Would these ADAs by binding to drug and signalling through FC also be able to cause hypersensitivity reactions that can be fatal to patients, or what's the mechanism of action here?
So 1% of rituximab patients for example die due to ADAs, do I understand this number correctly?
If the dose you mention is right this is totally unjustified. Just exposing people to a level of drug that will have no effect. I may be wrong but that dose sounds like a deliberate confidence trick.
From what I was told in a mail, they've seen low grade CRS after initial dosing (thus pretreatment with prednisolone and paracetamol) and longer term hypogammaglobulinemia - would this not be an indication for efficacy even at these low doses?