Filgotinib (JAK1 inhibitor) future of CFS/ME treatment?

[dr. Arf]

I wonder what 12mg of Baricitinib is compared Rinvoq and Filgotinib? I took that dose today. Prior been on 8mg for 10 days, and 4 mg about 5 or 6 days so far,. The upper dose of Baricitinib is 8mg so I’m probably in uncharted territory unless anyone has seen anything written on a 12mg dose?

I’ll do this for a week more, and maybe if I feel ok will try do to weeks. But probably too risky to continue after that.

I cannot give you an answer, but these Pharmacokinetics graphs attached might give you some insights.
– I do not remember now where I got it from but I think it was from a Paper Study based on comparing new Filgotinib versus other Jak-Stat inhibitors.

It measured JAK-1 inhibition overtime - hours:
- FIL = Filgotinib
- BARI = Baricitinib
- UPA = Upadacitinib (Rinvoq)
- TOFA = Tofacitinib (Xeljanz)

I don’t know how they exactly measured this, and the devil is in the detail.
Also all these Jak-Stat inhibitors have (slightly) different methods of action, so you cannot compare this one on one.

 

[dr. Arf]

To clarify, if 200 mg of Filgotinib has equal potency with 15 mg of Rinvoq, then 500 mg of Filgotinib would be equivalent to 37.5 mg of Rinvoq.

Do you remember what he meant exactly with with Potency? :
– both JAK1 inhibition and JAK2 inhibition?
- possibly a better / different / longer consistent form of inhibition?
- maybe crossing the blood brain barrier?
- Other factors ?

I know the Pharmacological Parameters Ki and Vd are important, per dosage - To give a hint about the fraction of cells taking up the drug:
Ki = the inhibition constant of the drug for its target
Vd = effective volume of distribution of the drug

 

[dr. Arf]

Just to add: these are the 2 different ideas / train of thoughts for the how Jak-Stat inhibitors.could improve ME CFS patients:

1) K. de Meirleir (KDM)
- KDM thinks filgotinib will inhibit various JAK /STAT pathways so that the dendritic cells in the MICROBIOME will be extinguished and intestinal immunity will be given a chance to normalise.
- Long term courses are required to see effect

2) Itaconate Shunt Theory - Robert Phair
If the issue lies with the itaconate shunt, it needs to be ensured that an effective concentration reaches nearly all the cells trapped within that pathway. Specifically, it’s crucial to cross the blood-brain barrier with the drug.
The itaconate shunt theory suggests that the severity of the disease and its symptoms are related to the quantity and types of cells affected by the shunt. Thus, symptom alleviation is contingent on delivering sufficient medication to a significant number of affected cells
The aim of therapy is to reach or exceed the Ki concentration at the drug’s action site. Extending the duration of treatment is possibly/maybe unnecessary for longer illnesses or higher severity.
What is essential is that an effective concentration of the inhibitor is present in the cytosol of the affected cells.

- So following this last theory, a Short course(s) of High dose could break Itaconate Shunt (stop all interferon alpha (??) signaling - if I understand correctly)

 

[Sushi]

Do you remember what he meant exactly with with Potency? :

I don't know but I may have the opportunity to ask soon.

 

[dr. Arf]

I don't know but I may have the opportunity to ask soon.

Yes, please do so. Thanx.
it might be interesting for patients that have access to Jak-Stat inhibitors.

 

[Clchalbaud]

Hey it took about 6 months to see noticeable effects.
Then after one year I reached my peak and now I feel better when weaning off.

I was on 1 tablet per day for a year, now I'm already down to 1 tablet per 72 hours and planning on going to 1 per 4 days soon and hopefully I can completely stop this year.

It's incredibly powerful and has changed my life!

Filgo made it possible for me to stop taking both Gammanorm and Normix which previously I could not live without for even 1 day.

Hi Sam d.
Where you on 1 x100mg or 1x200mg tablet per day?
If anyone else knows please let me know thanks .

 

[dr. Arf]

Where you on 1 x100mg or 1x200mg tablet per day?

I know he was on 200 mg a day

 

[Sushi]

FYI, I just posted a thread on a new study of Baricitinib on Long Covid patients—it is recruiting. https://forums.phoenixrising.me/thr...icitinib-for-long-covid-now-recruiting.92812/

 

[Sushi]

Here is the personal story of the lady that is in remission from Rinvoq.

It’s the same anecdote as in the thread above.

Very interesting what she mentions about cytokine-storm.
- what strikes me as odd is that normally a cytokine storm comes with fever, high heart rate, etc.

https://www.healthrising.org/blog/2024/11/20/jen-rinvoq-chronic-fatigue-recovery/

Hey thanks for posting this. How about posting it as a thread though, so it would get more attention. You would just have to delete this post and then repost as a thread in this section.

 

[Clchalbaud]

I cannot give you an answer, but these Pharmacokinetics graphs attached might give you some insights.
– I do not remember now where I got it from but I think it was from a Paper Study based on comparing new Filgotinib versus other Jak-Stat inhibitors.

It measured JAK-1 inhibition overtime - hours:
- FIL = Filgotinib
- BARI = Baricitinib
- UPA = Upadacitinib (Rinvoq)
- TOFA = Tofacitinib (Xeljanz)

I don’t know how they exactly measured this, and the devil is in the detail.
Also all these Jak-Stat inhibitors have (slightly) different methods of action, so you cannot compare this one on one.

Think it was obtained form here…

https://www.researchgate.net/public...rthritis_An_Overview_from_Clinical_Trials#pf4

 

[Aidan Walsh]

It may take a great deal of time to yield any positive results but let’s not forget reports of an individual in Australia being “cured” within 3 days. Ron Davis’s words not mine.

@DonPepe What was the patient on to be cured in 3 days in Australia? ME/CFS or LC?

 

[Aidan Walsh]

yes he did order a bunch of test as he does during every consult but I almost never take them to save costs. I wanted to save as much money as possible for the treatment itself. Plus you very quickly get a feel for how good or bad you are doing. If you would really feel a lot worse then just stop taking it. Otherwise, be prepared to sit through some discomfort. It's worth it in the end

Are you still on this medicine now and dosage how long? & Are you fully recovered?