Open 2022 Pilot study in Norway - Daratumumab in ME/CFS

Where does it say 4 injections?

As far as I know the 2 week interval is an arbitrary thing. For rituximab it arose when we doubled up the dose that had been given four times weekly so that it was given twice and the two week gap was purely due to the need for a two week gap between concomitant cyclophosphamide doses. I cannot think of any pharmacodynamic reason. These antibodies can probably be given as a single large dose but if given subcutaneously you probably need a small initial test dose.

The total dose for rituximab was again pretty arbitrary. There was very weak evidence for a dose response relation but no formal assessment of optimal dose was made.

The prime driver of all these doses is company profit.

 

So basically what you’re saying is you could:
- give a test dose Dara
- followed by 1 BIG dose
- being more effective

1 High dosage has the same risk on side effects / adverse events ?
Through IV infusion is most cost effective (basically lower dose) ?

 

Don't take my word for it because there may be things about this antibody that are importantly different.

But in general terms there seems to be no particular reason not to give all the antibody at one go, unless you are wanting to remove new plasma cells that have formed after the original dose. The reasoning around strategy of this sort is very complex and not well understood.

If antibody is given IV then adverse reactions can be monitored for over an hour or so before giving the full dose rapidly. To my mind this is much safer than giving subcutaneously when adverse reactions might occur hours after you have given the whole dose. IV also gives higher bioavailability.

The adverse effects we saw with rituximab were generally with the first dose and did not appear to be dose dependent.

 

Seems like there are more adverse reactions with IV than subQ

https://www.pharmacytimes.com/view/...uce-subcutaneous-daratumumab-observation-time

 

Very likely more noticed since someone is watching carefully!
In biological terms the risk has to be much higher with subcutaneously because you cannot stop more being absorbed if you run into anaphylaxis.

The secret with IV is to take the slow early stage very seriously and watch carefully as the rate is increased. It may be safer to give subcutaneously if IV administrators are lazy but I prefer careful IV administrators.

It isn't the number of reactions that matter. It is the number that get to the potentially lethal stage without you being able to stop drug going in.

 

It looks as if the subcutaneous version is a different formulation to the IV type, too, so that might account for some differences in adverse events.

But there could have been a dozen other factors at play—age, sex, comorbidities, history of allergy, other meds—so it's hard to compare properly unless someone actually captures the information.

 

I think the antibody will be the same - the bit that is doing the job.
The subcutaneously preparation has some extras to help get through the subcutaneous tissue but that would be expected to add some potential reactions. The IV will have very little except perhaps preservatives that would be needed for both.

 

Don't several pharmaceutical companies also have a hyaluronidase version to increase their market as one is supposedly more convenient? I know Efgartigimod also has a version with hyaluronidase to treat certain autoimmune diseases, with the sole purpose supposedly being convenience. They seem to first conduct studies with the IV version and later on, when successful then try to obtain approval for the subcutaneous version. For Myastenia Gravis they had a trial that supposedly showed that both formulations do the same thing and have a similar safety profile in said condition.

 

If I were to add a point of caution regarding using steps (which Im a big advocate for together with SF-36), it would be that it is still possible for many ME/CFS-patients like myself to walk 6k steps each day, but with progressive symptoms. I often walk until I almost can't stand anymore, and I guess the step monitoring does not factor in this willpower-element. PEM during walking should probably be reported in a study like this (if it already is, my apologies).

 

This is important, and the opposite's equally true: it's perfectly possible for someone to be significantly better but not increase their steps. If they went back to work there could even be a decrease.

What matters is the overall picture of what they can do. To get around the problem of people substituting activities rather than doing more of them, you'd need to capture a diary and data from wearables in the months before a trial starts. Then repeat it shortly after the intervention and again at six, twelve, and eighteen months.

 

Does anyone know how to score the DSQ SF test?

https://www.leonardjason.com/wp-content/uploads/2021/05/DSQ-SF.pdf

ETA: guessing that you add together the scores for the first 14 questions in the frequency and severity columns.

 

Follow up study?
https://www.s4me.info/threads/norwa...o-severe-chronic-fatigue-syndrome-2025.43715/

 

Looks like it because it says that recruitment hasn’t started so it can’t be the pilot.

 

I'm admittedly ignorant about clinical trials. It says it runs from 2022 until December 2026. Do we really have to wait another year for the results? I don't know how long recruitment takes and in what intervals they've received injections. I assume they do a follow up some time later to study long-term effects. Is there any chance this could be completed sooner or has it been completed already if they are already planning the next study?

 

We'll probably have to wait for the final results to be written up, as they'll need to follow people up afterwards. It still looks like an early stage trial (small cohort), so they might only be enough to justify or rule out a larger study.

 

The pandemic is never going to go away, in essence, for all that people refer to Covid now as endemic. Does this drug block people's ability to respond to infection as well as to vaccination?

Either way, can this drug ever be safe now?

 

The answers may be complicated but this is a reminder that there is a need to be clear exactly what is expected to be achieved with a drug like this and whether in the longer term it can realistically be expected to do it.

 

Do you foresee other kinds of drugs being effective that wouldn't have this kind of downside, as per your upcoming paper about your theory?

Just wondering also when you're hoping to post your theory - I think we're about three weeks into the month you estimated but plans go to hell as soon as the first shot is fired, according to Jack Reacher.

 

Potentially, yes.

The theory is shared with Jo Cambridge and we want to make sure it is well constructed. Time frame is not fixed although I was hoping it would be pretty soon.

 

This presentation mentions they have a dara RCT in the works (6 months ago).

Given the recent announcement of what looks like a smaller dose response study, is it likely the study got cut down to that, or that this is happening side by side (or right before) the RCT.