• Welcome to Phoenix Rising!

    Created in 2008, Phoenix Rising is the largest and oldest forum dedicated to furthering the understanding of, and finding treatments for, complex chronic illnesses such as chronic fatigue syndrome (ME/CFS), fibromyalgia, long COVID, postural orthostatic tachycardia syndrome (POTS), mast cell activation syndrome (MCAS), and allied diseases.

    To become a member, simply click the Register button at the top right.

Has anyone tried Otezla?

MonkeyMan

Senior Member
Messages
406
Was reading about a patient who recovered entirely from antivirals plus Otezla. Anyone here try Otezla, or hear of Otezla being useful for CFS, or any trials on it?
 

Dude

Senior Member
Messages
190
I came across the medication via Björn's thread and wondered why he was given Otezla? The active ingredient in it is called apremilast and is used to treat chronic plaque psoriasis and psoriatic arthritis. The active ingredient is also used to treat oral aphthae associated with Behçet's syndrome.

I haven't found any other connection to MECFS. So I did a bit of research and it's actually a very interesting drug in connection with MECFS.

Unbenannt.PNG

Source
Apremilast leads to an increase in intracellular cAMP levels in synoviocytes by inhibiting PDE-4, resulting in a reduced release of pro-inflammatory TNF-α

TNF-alpha has been shown to be often elevated in the serum of patients with ME/CFS compared to non-ME/CFS controls and is theorized to play a role with other cytokines in symptom presentation and severity.

Bruce Patterson posted a tweet: "TNF alpha which is elevated in long COVID inflammation reduces serotonin levels. Reduce the inflammation and levels will normalize"

From MEPedia: Several clinical trials have been proposed for the use of a tumor necrosis factor-alpha inhibition drug, etanercept, in ME/CFS. Results have been mixed. A pilot study in 2001 by K. Lamprecht using etanercept on six CFS patients reported considerable benefit, but the study was not expanded.
Rapid improvement in severe long COVID following perispinal etanercept.

The thing is, Apremilast has only been approved since 2016. That means it couldn't be tested before then for MECFS. But at least it seems to be relatively safe

So maybe, if you are dealing with low serotonin Level, it is worth a shoot.
 

hapl808

Senior Member
Messages
2,137
I do know someone with ME/CFS who took Otezla - for psoriasis rather than ME/CFS. I believe they had such negative mental health effects from it that they eventually stopped, despite it being helpful for their psoriasis. I don't believe it had any impact on their ME/CFS symptoms.
 

Hoosierfans

Senior Member
Messages
400
I came across the medication via Björn's thread and wondered why he was given Otezla? The active ingredient in it is called apremilast and is used to treat chronic plaque psoriasis and psoriatic arthritis. The active ingredient is also used to treat oral aphthae associated with Behçet's syndrome.

I haven't found any other connection to MECFS. So I did a bit of research and it's actually a very interesting drug in connection with MECFS.

View attachment 52823
Source


TNF-alpha has been shown to be often elevated in the serum of patients with ME/CFS compared to non-ME/CFS controls and is theorized to play a role with other cytokines in symptom presentation and severity.

Bruce Patterson posted a tweet: "TNF alpha which is elevated in long COVID inflammation reduces serotonin levels. Reduce the inflammation and levels will normalize"

From MEPedia: Several clinical trials have been proposed for the use of a tumor necrosis factor-alpha inhibition drug, etanercept, in ME/CFS. Results have been mixed. A pilot study in 2001 by K. Lamprecht using etanercept on six CFS patients reported considerable benefit, but the study was not expanded.
Rapid improvement in severe long COVID following perispinal etanercept.

The thing is, Apremilast has only been approved since 2016. That means it couldn't be tested before then for MECFS. But at least it seems to be relatively safe

So maybe, if you are dealing with low serotonin Level, it is worth a shoot.
I’d have to look up the differences, but one of the drugs I’ve been looking at is Ibudilast…which is a selective PDE-4 inhibitor like Apremilast is. I read the same report you did, and when I looked up Apremilast I was like “wait a sec, that’s similar to Ibudilast.”

I have some Ibudilast in my cabinet…will try it after a few other things.

Ibudilast , blocks Toll Receptor 4, blocks NFKappa Beta, TNF-a, IL-6, IL-1b, IL-10, nitric oxide and ROS…all of that calms down glial cells. It’s used in Japan for pain conditions and “post stroke dizziness.”

It’s one of the two drugs that they are using in the big RECLAIM long COVID study in Canada:
https://clinicaltrials.gov/study/NCT05513560
 

Hoosierfans

Senior Member
Messages
400
Curious how that works out - one of the things I've been interested to try.
I’ll keep this thread posted if I try it. Maybe someone who is better at the pharmokenetics and mechanisms, like @Hip can weigh in on the differences between Otezla (Apremilast), Enterecept and Ibudilast.

FWIW I chose Ibudilast when looking for TNF-a blockers (bc my levels are high), but not getting anywhere with rheumatologists…most flat out refused to see me, one did see me but dismissed my inflammatory markers.

All this despite having two docs on my team (my psychiatrist and my immunologist) who think a lot of my issues, including severe depression, are inflammation driven. But as they’ve told me, they don’t prescribe these drugs…rheumatologists do…so unless you can convince a rheumatologist to treat your CFS or depression, etc, I don’t know how you’d get your hands on the TNF-a blockers. So my only recourse was to go with the one I could order online from a peptides / research chemicals supplier.
 

Dude

Senior Member
Messages
190
@Hoosierfans sounds interesting, if they are testing it at Long covid, there must definitely be something to it. I ordered Aprezo from alldaychem. It seems to me to be relatively safe as far as side effects are concerned. I'll give it a try. I haven't had my TNF A tested, but I have low serotonin, which could indicate elevated TNF A. Unfortunately it will take some time, as I always have to order it in England.
 

Hoosierfans

Senior Member
Messages
400
@Hoosierfans sounds interesting, if they are testing it at Long covid, there must definitely be something to it. I ordered Aprezo from alldaychem. It seems to me to be relatively safe as far as side effects are concerned. I'll give it a try. I haven't had my TNF A tested, but I have low serotonin, which could indicate elevated TNF A. Unfortunately it will take some time, as I always have to order it in England.
Wow I didn’t realize you could get Apremilast online. I also didn’t realize it’s oral — one of the reason my docs gave me for “go see a rheumatologist for those meds” is that they are / were administered via IV and required monitoring.

I’ll have to pin this idea and chat more w my docs about it.

So here’s a couple of resources re Ibudilast and rationale in LC.

1. See pic below— looks like they are particularly interested in the TLR 4 antagonism.

2. Video where they discuss Ibudilast (around the 20:00 mark) (havent watched it yet:

3. TLR 4 is triggered by LPS, and leads to an inflammatory cascade that includes TNF-a (I.e. block TLR 4 and you block TNF-a): https://www.pnas.org/doi/10.1073/pnas.2011667117#:~:text=Binding of LPS to TLR4,ultimately pathogen destruction (3).

4. It’s also being studied in MS, and this write up gives a good description of its mechanisms. Importantly, it’s able to cross the BBB (yay!): https://multiplesclerosisnewstoday.com/ibudilast-mn-166-multiple-sclerosis/
 

Attachments

  • 8249D630-654B-4F35-B555-D58ABA62CDE5.png
    8249D630-654B-4F35-B555-D58ABA62CDE5.png
    853.9 KB · Views: 0

Hoosierfans

Senior Member
Messages
400
@Dude don you know why Klimas and others have chosen Etanercept to study in GWI and ME / CFS? I couldn’t find anything online about why they’ve chosen it specifically. It’s a different kind of TNF-a blocker from the “big 4” — Humira, Remicade, Simponi, Cimzia in terms of mechanism but I’m not sure that why they chose it.
 

Dude

Senior Member
Messages
190
@Dude don you know why Klimas and others have chosen Etanercept to study in GWI and ME / CFS? I couldn’t find anything online about why they’ve chosen it specifically. It’s a different kind of TNF-a blocker from the “big 4” — Humira, Remicade, Simponi, Cimzia in terms of mechanism but I’m not sure that why they chose it.
Dont know,
Maybe it was because of this small Study:
https://pubmed.ncbi.nlm.nih.gov/35791687/
and the fact that it has shown positive results before in MECFS patients.
 

Hoosierfans

Senior Member
Messages
400
Dont know,
Maybe it was because of this small Study:
https://pubmed.ncbi.nlm.nih.gov/35791687/
and the fact that it has shown positive results before in MECFS patients.
Hmmm, interesting. It’s great that it was so effective in this N=1. Frustrating that it’s a powerful biologic administered in probably the most invasive way possible…..

Just thinking out loud but given that framework, future studies on it would have to be pretty powerful and convincing for the treatment to ever be accessible (read: (a) getting a doc to prescribe it and (b) getting insurance to cover it). So I think we are a long way away from perispinal entercept being a viable treatmebt.

That said, I guess the best we can do for now is doing what you and I are doing — looking for similar meds that can be easily administered and either easily prescribed or available somewhere without a script.

Curious how your Otezla experiment goes…..😊
 

Hoosierfans

Senior Member
Messages
400
A bit more info:

Science behind perispinal etanercept:
https://bpspubs.onlinelibrary.wiley.com/doi/10.1002/prp2.926

The issue with TNF-a blockers / biologics appears to be there size as very large molecules. So when they are administered “normally”, they don’t cross the BBB. However, in the early 2000s /2010s some researchers looked into injecting Etanercept (no idea why they chose that one) into the perispinal venous space and then inverting patients — and found that this allowed the drug to get into the brain:

“In addition, collections of observational studies using this perispinal method of delivering etanercept to the brain, beginning in 2010, have reported impressive outcomes in treating post-stroke neurological dysfunction in many patients [Citation13Citation17]. To summarize a recent text [Citation12] that illustrates and quotes additional anatomical detail, perispinal injection followed by a short period of head-down positioning [Citation10] may therefore be expected to enable etanercept to be delivered to the brain through the choroid plexus, the cerebral venous system, and the cerebrospinal fluid, thus bypassing the BBB. Such a route is consistent with the reported presence of labeled etanercept within the brain in experimental studies.”

https://www.tandfonline.com/doi/full/10.1080/14737175.2020.1727742?scroll=top&needAccess=true

So it sounds like Klimas etc are building on previous research in stroke, and a unique way of getting Etanercept into the brain that has already proven safe. So *maybe* since there are good studies on this treatment and methodology in stroke, the approval process may be a bit smoother and effective for LC and / or ME / CFS.

In the meantime we can try normal TNF-a and microglial de-activators via normal routes, while searching for a unicorn doctor that will inject us w Etanercept off label and hang us upside down. 😜