Filgotinib case studies

[Woodyrob]

Hi


Hi

I’m in the uk.

Would you try Baricitinib if you could get it or wait for the more targeted JAK STAT1 inhibitors?

 

[DonPepe]

I’m doing ok on Mestinon and Valcyte for now. If improvement stops I may move onto Rinvoq.

 

[Inez]

I read in a different platform someone say quote “KDM expect his patients take Bactrinib at least 6 months, that's when most of the effects are noticeable.”
(Apparently, KDM is a ME/CFS doctor or a clinic somewhere)

Which means I can’t do that because I have that awful drug hypersensitivity intolerance issue to Baricitinib (same issue with several but not all medications) . However I did find that if I combine a low dose of dexamethasone with Baricitinib then the awful drug intolerance sensations go away. I checked to see if humans had already tried that combination. And it is done for people in the anccute inflammatory Covid stage. So at least I know it’s not unheard of.. but there’s no way I could do that for six months. As too hard on the body. But I’d do it for a few weeks.

So, I’m liking what you are saying about Rob Phair’s escape velocity being needed with a higher dose. Maybe Baricitinib’s dose range is too low for ME/CFS. It’s broadness is why it’s lower perhaps.

Reading into what you say, we aren’t trying to turn down immunity to get rid of rheumatoid arthritis or other inflammatory issues which Baricitinib is designed for. We are trying to turn off the shunt long enough it clicks innate immunity back to natural homeostasis . Which if we boosted the dose, it may actually work.

I’m not sure I want to be the first to try that though lol

Do you have Baricitinib?

Yes I'm planning on trying it when if we learn more about which dosage could be effective for ME. If it's just 3 days of a higher dose I imagine it wouldn't be damaging? I don't know though.

 

[Woodyrob]

Does baricitinib take 6 months+ to work at the dosage of 2 or 4mg as prescribed for autoimmune conditions or much faster if at the dosage needed to escape itaconate shunt? Do we know what that dosage is yet?

I don’t know what escape velocity dose would be but for people with acute COVID inflammatory stage they took 8mg for 14 days. I read a few studies and 8mg appears to be the highest dose I’ve seen so far.

Like you mentioned for autoimmune conditions like rheumatoid arthritis the ongoing maintenance dose is 2mg -4mg.

So who has the balls to take 8mg for 14 days or more?


>>>>

Impact of high dose of baricitinib in severe COVID-19 pneumonia: a prospective cohort study in Bangladesh <<<<​

https://bmcinfectdis.biomedcentral.com/articles/10.1186/s12879-021-06119-2

Conclusion​

The daily high dose of baricitinib in severe COVID-19 results in early stabilization of the respiratory functions, declined requirements of critical care supports, reduced rehospitalization with mortality rate compared to its daily usual dose.

 

[Sushi]

We are trying to turn off the shunt long enough it clicks innate immunity back to natural homeostasis . Which if we boosted the dose, it may actually work.

So it could either be a higher dose or longer duration that turns off the shunt? Do we know whether Baricitinib, Filgotinib or Rinvoq is the best suited for our purposes?

 

[Woodyrob]

So it could either be a higher dose or longer duration that turns off the shunt? Do we know whether Baricitinib, Filgotinib or Rinvoq is the best suited for our purposes?

I’m thinking it will be either Filgotinib or Rinvoq as they are more potent and are more narrowly targeted. I’m definitely thinking higher dose as the idea is to turn off the Itaconate shunt “positive feedback loop” (Robert Phair talked about) which was caused by interferon alpha signalling too much. So I don’t think a rheumatoid arthritis maintenance dose would be high enough. Because they are doing a balancing act between having enough immunity to be able to be out in public and enough immune suppression to stop rheumatoid arthritis symptoms caused by these signalling pathways. So their dosage is partially allowing some signalling to carry on. We don’t want that, as are trying for only a short time to turn that off as much of the signalling pathway as possible instead. Which specific pathway it is seems to be that ones that Filgotinib or Rinvoq target hence called JAK STAT1, but Baricitinib covers those same pathways and more, which could be why it’s not as potent (JAK STAT 1 & 2 although I’ve read 1 & 3)

So yes, I’m thinking a dose increase plus finding the right JAK STAT inhibitor.

Rinvoq (Upadacitib) is $3,000 NZD for one month’s supply at standard dose
and Filgotinib I can’t get here.

I’ve heard rumours it takes 6 months on Baricitinib for people with ME/CFS to improve. And that’s a long time and not practical for people who can’t tolerate the drug. It’s cheaper here though at $189 for 3 months supply. Maybe Baricitinib could work at a higher dose

Attached again is the graph showing what each drug targets

 

[Sushi]

So I don’t think a rheumatoid arthritis maintenance dose would be high enough. Because they are doing a balancing act between having enough immunity to be able to be out in public and enough immune suppression to stop rheumatoid arthritis symptoms caused by these signalling pathways. So their dosage is partially allowing some signalling to carry on.

I read a very large Rinvoq FB group and while some start at 15 mg and others start at 45 mg (and stay on 45 for about 3 months) patients don't report much difference in side-effects and frequency of infections and reactivated viruses whether they are taking 15 mg, 30 mg, or 45 mg. So while our strategy would be different, it is interesting that the side-effects related to different doses doesn't seem to be that different.

 

[Thinktank]

I have been offered filgotinib by my gastroenterologist to prevent future IBD-flares, to be take indefinitely.
Is there any news about JAK-inhibitors as a treatment for ME/cfs? Surely it must have been tried by quite a few patients by now.

 

[Woodyrob]

I have been offered filgotinib by my gastroenterologist to prevent future IBD-flares, to be take indefinitely.
Is there any news about JAK-inhibitors as a treatment for ME/cfs? Surely it must have been tried by quite a few patients by now.

You are lucky to get that drug as that’s the one that worked best.


I haven’t heard any more apart from Jannet Dafoe saying Robert Phair and Ron Davis know of 2 people who “greatly improved “ on JAK STAT inhibitors


So still the same information as above. one person who took it was cured though. They took it about a year ago. A very quick improvement too of 3 days.


Another person took a similar drug and “Greatly improved” both patients stopped taking the medications pretty early too.


Others on JAK STAT inhibitors haven’t had any improvement so either they have different mechanisms for the same disease or its dose dependent.


Meaning the higher the dose the more likely we are going to be able to ‘temporarily’ turn off this “immune signalling pathway’ long enough that the ME/CFS patient can get out of the eternal ‘feedback loop’ that won’t turn off.


But boosting a dose beyond its standard dose is risky. I looked up Baricitinib (similar drug class) and found a couple of unrelated studies (nothing to do with ME/CFS) where they doubled the standard dose for 14 days while on a steroid, And those patients were fine.


Also importantly if you can’t tolerate this medication maybe still keep getting it to build up a stock pile of it because it’s very expensive, so if it’s been subsidised for your lBS condition , maybe keep it for other people with ME/CFS because it won’t be subsidised for that until proven, which could be years away.


Or do what I’m doing (with Baricitinib) and that’s taking it with prednisone and amazingly I can tolerate the Baricitinib,


Taking with a steroid is more risky for infection. But the key to what I’m doing is isolating and short term use. But will try get to a higher dose. (I’m at day 4 or 5) And I start a higher dose today.


So the dose will be above the standard maintenance. Today I’ll be going to 6mg
Fingers crossed.

I know at 4mg it’s not working for ME/CFS because I can feel a sore throat developing from exertion the other day


As for you I’d stick to what your doctor said to do first. Then if no improvement, I’d boost it a little. But that’s me, best to talk to a doctor about these things. Although I doubt a doctor would agree to what I’m doing, and the reason is they don’t actually understand how damn severe ME/CFS is. If they did they’d weigh up the risks.

 

[Sushi]

I haven’t heard any more apart from Jannet Dafoe saying Robert Phair and Ron Davis know of 2 people who “greatly improved “ on JAK STAT inhibitors

Note: the 3 patients with substantial improvement or remission had these results after stopping. I think that more people will be experimenting with JAK 1 inhibitors and hopefully there will be more news in the future—the sooner the better.

 

[Woodyrob]

Note: the 3 patients with substantial improvement or remission had these results after stopping. I think that more people will be experimenting with JAK 1 inhibitors and hopefully there will be more news in the future—the sooner the better.

UPDATE to all who are following

I’ve been on Baricitinib for 16 days. And on a double dose (at 8mg) for 10 days so far.

No difference between the two doses. But also no improvement yet. Only half way through this experiment though

So today I increased to 10mg

I’m on prednisone at the same time as Baricitinib (reason mentioned above).
prednisone knocks me around a little but it’s something I can handle ok at the moment.

I think maybe the Baricitinib dose is still too low.

I see the main side effects of higher dosing is more likely to risk an infection, which i haven’t had. I am isolating with two dogs (which aren’t overly clean so I must still have innate immunity)

The other side effect to worry about is anemia, But that more long term use.

I might go to 12mg the next two weeks unless an infection stops me sooner

I have to be off these meds anyway by 8th of November as have to stop isolation as will be around people.

Which will be only 5 weeks. So probably best to crank it up in this last stretch.

I don’t hold much hope for Baricitinib though as I think it’s too broad JAK 1 & 2 as inhibits a wide spectrum of cytokine communication. Which could mesn the dose is less potent than the Filgotinib or RINVOQ because a higher dose on them wouldn’t affect as many types of cytokines, so you could potentially really push up the dose and shut off a narrower part of innate immunity on them.

We kind of know by that chart (posted earlier) what that part that is because like Sushi said we know two or three people who were cured used those specific JAK STAT 1 inhibitors

Has anyone else tried boosting the dose of any JAK beyond its normal dose? Or am I a lone wolf

 

[Sushi]

Has anyone else tried boosting the dose of any JAK beyond its normal dose? Or am I a lone wolf

Thanks for sharing this— the more personal experiences we hear the more we learn. I am in touch with an academic researcher who is interested in the properties and effects of JAK inhibitors and learned that the dose of Rinvoq that is equivalent to 200 mg of Filgotinib, is 15 mg—the lowest dose of Rinvoq available.

I have also been reading a very large Facebook group for Rinvoq users (about 9000 members) and many start at a loading dose of 45 mg and then move down to 30 or 15 mg after a few months. They do report more side effects on higher doses and their doctors do require lab tests at least every three months to check for high or low white or red blood cell counts, changes in cholesterol, and changes in liver and kidney function – all of which have been commonly reported. Of course, the members of this group are taking Rinvoq for a variety of different diagnoses which most of us would not have. They are also taking it as part of a continuous treatment plan.

 

[Woodyrob]

Note: The information below really needs discussed with someone that knows more about immune suppressing drugs. So talk to a professional. This is just what I did to beat ‘Drug hypersensitivity’ (aka Drug Intolerance)

I forgot to update you all. Unfortunately I didn’t improve on Baricitinib, but I was on it only a short time, for just 31 days, but I eventually I got up to 5 times the dose 4mg x 5 =20mg (I prior checked the max known dose of toxicity testing that showed not to have any increased side effects in participants after 10 days of use). So I did the last 7 days at that dose, of that 30 day period.

Interestingly I also didn’t feel any more symptoms at that dose than the lower standard dose. No infections either, as risk is higher. And I am living in a filthy caravan with two small dogs

So no improvement. But maybe a month is too short. Or possibly Baricitinib isn’t potent enough to fully turn off IFN & other cytokine signalling. Although that dose was high

The interesting thing was I was very intolerant to Baricitinib from the very beginning tiny first dose, as I had the immune form of Drug Hypersensitivity, but that can be treated with glucocorticoids. So by taking 15mg Prednisone along with Baricitinib I could quickly tolerate and turn off the ‘Drug Hypersensitivity’ Then after a week I was able to drop the prednisone dose down to 7.5mg. I presume that’s because Baricitinib was also dampening immune response so maybe it also it helped a little in being able to tolerate itself.

Note: there are a few types of immune induced Drug Hypersensitivity, some of them are T Cell related and one gives Lupus like symptoms. I get some of those same symptoms (including the rejection symptom). So knowing that glucocorticoids turn that response off, I gave them a try, and they worked

This possibly means pwME who are intolerant of many medications, (and hopefully not also glucocorticoids as some are) could temporarily take prednisone or even dexamethasone to stop that awful drug hypersensitivity issue. While the other drug cures them. (Need check drug interactions first)
Also there maybe other meds that turn off drug hypersensitivity

The problem is how long can someone with ME/CFS safely take a glucocorticoid? (Some can’t at all) For those that can, hopefully 2 or 3 months is doable. Also at that duration needs a long wean off period too.
I stopped at 31 days because it’s much easier to wean off prednisone then than at 3 months.

Anyway at least I proved to myself drug hypersensitivity is beatable. and high dose Baricitinib was a breeze!

 

[ryanc97]

I can source Rinvoq at about 5 dollars a tablet so not expensive.

I source my drugs from a broker in India.

Hi Hi I’m in the uk.

 

[ryanc97]

Hey @DonPepe, where can you source Rinvoq from? I was interested in trying it. Would be happy if you could share your source.