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Hope for the future. Myofibroblast research.
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09/03/2013 06:40
stephenjeffrey 
09/03/2013 06:40
stephenjeffrey 

Re: Hope for the future. Myofibroblast research.

pia2some:
So now I'm curious and am looking around on the web. It's too late for me to look up much, but I did find this. I will not receive anymore Xiaflex, I know that much. But reading the details about this drug is scary. I'd feel much better if it had already been in use for decades. It is just too new.

"Because the therapeutic activity of Xiaflex is localized to the injection site and does not require or result in systemic exposure, the primary pharmacodynamic activity of the drug could not be evaluated in subjects and, therefore, such studies have not been undertaken.

Data from one Phase I and one Phase II Study confirmed that there is no quantifiable systemic exposure following a single injection of Xiaflex (0.58 mg) into the cord of the affected finger in subjects with advanced Dupuytren's disease or following the subsequent procedure to disrupt the cord. There has been no evidence of systemic toxicity to date in the clinical studies conducted with Xiaflex administered through localized injection into the Dupuytren's cord. Results from the aforementioned clinical Phase I and II studies indicate that no detectable absorption of any Xiaflex-derived components occurs in subjects under the conditions of clinical use.

For these reasons, no clinical studies pertaining to tissue distribution, metabolism, excretion, plasma concentration-effect relationship, dose and time dependency, effect on hepatic or renal function, and drug-drug interactions have been performed with Xiaflex.



Xiaflex is generally expected to be confined to the injection site rather than to undergo systemic distribution; however, extravasation could occur. Injection-site reactions occurred in 35% of the patients who received Xiaflex vs. 5.6% placebo.

It should be emphasized that the pharmacodynamic mechanism of action of Xiaflex is the destruction/digestion of collagen. As long as this process is controlled and remains localized to the tissue area/volume of interest the risk/benefit profile of this therapy could be acceptable. However, should the drug reach adjacent tissues, such as nerves; blood vessels; cartilage and bone; or muscle, the risk of extensive irreversible damage cannot be ruled out.


A statement has been added to the Warnings and Precautions section of the Product Monograph describing that Xiaflex contains foreign proteins and patients develop anti-drug antibodies in greater proportions and higher titers with successive Xiaflex injections."

http://www.hc-sc.gc.ca/dhp-mps/prodpharm..._147788-eng.php

~ dawn

Hi Dawn thankyou for finding this research, I hope everyone considering xiaflex will read it BEFORE they consent to the injections.

09/04/2013 14:29
JohnG 
09/04/2013 14:29
JohnG 
Re: Hope for the future. Myofibroblast research.

I found some info on that Oxford University project.

The professor is Jagdeep Nanchahal

Here's a publicity that says they're using a type of rheumatism drug called antitumour necrosis factor (TNF).
http://www.isis-innovation.com/news/show...ens_Disease.pdf

Here's a paper Nanchahal wrote recently:
http://www.nature.com/jid/journal/vaop/n...id2013219a.html
It hints at using an unspecified "inhibitor" to hinder the disease in a test-tube. I'm afraid this paper is a bit harder for me to understand than most of the Dupuytren's scientific literature.

09/04/2013 15:09
wach 

Administrator

09/04/2013 15:09
wach 

Administrator

Re: Hope for the future. Myofibroblast research.

Great find. Thank you, John! I am in contact with Nikolaos Chalkias and hope to hear more Details soon. We need to keep in mind that this is still lab Research and far from a treatment stage.

Wolfgang

JohnG:
I found some info on that Oxford University project.

The professor is Jagdeep Nanchahal

Here's a publicity that says they're using a type of rheumatism drug called antitumour necrosis factor (TNF).
http://www.isis-innovation.com/news/show...ens_Disease.pdf

Here's a paper Nanchahal wrote recently:
http://www.nature.com/jid/journal/vaop/n...id2013219a.html
It hints at using an unspecified "inhibitor" to hinder the disease in a test-tube. I'm afraid this paper is a bit harder for me to understand than most of the Dupuytren's scientific literature.

09/05/2013 00:08
moondanc 
09/05/2013 00:08
moondanc 
Re: Hope for the future. Myofibroblast research.

stephenjeffrey:
pia2some:
So now I'm curious and am looking around on the web. It's too late for me to look up much, but I did find this. I will not receive anymore Xiaflex, I know that much. But reading the details about this drug is scary. I'd feel much better if it had already been in use for decades. It is just too new.

"Because the therapeutic activity of Xiaflex is localized to the injection site and does not require or result in systemic exposure, the primary pharmacodynamic activity of the drug could not be evaluated in subjects and, therefore, such studies have not been undertaken.

Data from one Phase I and one Phase II Study confirmed that there is no quantifiable systemic exposure following a single injection of Xiaflex (0.58 mg) into the cord of the affected finger in subjects with advanced Dupuytren's disease or following the subsequent procedure to disrupt the cord. There has been no evidence of systemic toxicity to date in the clinical studies conducted with Xiaflex administered through localized injection into the Dupuytren's cord. Results from the aforementioned clinical Phase I and II studies indicate that no detectable absorption of any Xiaflex-derived components occurs in subjects under the conditions of clinical use.

For these reasons, no clinical studies pertaining to tissue distribution, metabolism, excretion, plasma concentration-effect relationship, dose and time dependency, effect on hepatic or renal function, and drug-drug interactions have been performed with Xiaflex.



Xiaflex is generally expected to be confined to the injection site rather than to undergo systemic distribution; however, extravasation could occur. Injection-site reactions occurred in 35% of the patients who received Xiaflex vs. 5.6% placebo.

It should be emphasized that the pharmacodynamic mechanism of action of Xiaflex is the destruction/digestion of collagen. As long as this process is controlled and remains localized to the tissue area/volume of interest the risk/benefit profile of this therapy could be acceptable. However, should the drug reach adjacent tissues, such as nerves; blood vessels; cartilage and bone; or muscle, the risk of extensive irreversible damage cannot be ruled out.


A statement has been added to the Warnings and Precautions section of the Product Monograph describing that Xiaflex contains foreign proteins and patients develop anti-drug antibodies in greater proportions and higher titers with successive Xiaflex injections."

http://www.hc-sc.gc.ca/dhp-mps/prodpharm..._147788-eng.php

~ dawn

Hi Dawn thankyou for finding this research, I hope everyone considering xiaflex will read it BEFORE they consent to the injections.

It cannot be emphasized enough to checkand double check-- there are too mnany if's, and's maybe's and not enough followup studies. We need studies with long terms results, recurrance rates, comparison of Xiaflex to NA and OHS NOT just a placebo.
Thank you Dawn for digging this out.

Diane

09/05/2013 00:34
pia2some 
09/05/2013 00:34
pia2some 
Re: Hope for the future. Myofibroblast research.

I totally understand that any drug has potential risks. Heck, if you read every patient insert that the pharmacy gives you and took every warning to heart, you'd never take any drug. So I get there are risks.

Like Diane says, though, I'm not comfortable taking the risks with Xiaflex until I see more follow-up data. I would like to see long term data on patients after they receive Xiaflex.

~ dawn

12/02/2018 12:56
spanishbuddha 

Administrator

12/02/2018 12:56
spanishbuddha 

Administrator

Re: Hope for the future. Myofibroblast research.

Phase 2A of the RIDD trial, repurposing anti-TNF for DD has just published a paper with promising positive results https://ridd.octru.ox.ac.uk/

Phase 2B of the trial continues, although they recently closed it to new participants.

12/02/2018 13:39
wach 

Administrator

12/02/2018 13:39
wach 

Administrator

Re: Hope for the future. Myofibroblast research.

Has that report been withdrawn? I only get a "Page not found" on that link.

Wolfgang

12/02/2018 16:52
spanishbuddha 

Administrator

12/02/2018 16:52
spanishbuddha 

Administrator

Re: Hope for the future. Myofibroblast research.

wach:
Has that report been withdrawn? I only get a "Page not found" on that link.

Wolfgang
This direct link works for me https://www.ebiomedicine.com/article/S23...0229-9/fulltext

12/03/2018 07:15
wach 

Administrator

12/03/2018 07:15
wach 

Administrator

Re: Hope for the future. Myofibroblast research.

This link now works for me as well. I am still curious how this treatment will help with Dupuytren's and what kind of side-effects it will have. It depends on what the cause of Dupuytren's is: if it is a wrong level of TNF then this therapy is probably very helpful. If the building of the cord is basically a natural, healthy process and the reason why it is built is something else (e.g. a nodule glueing the connective tissue) then affecting TNF levels might not be the best way and might have undesired side-effects. But clarifying that is what the trial is made for. Interesting in any case!

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Injection-site   research   Wolfgang   Xiaflex   isis-innovation   pharmacodynamic   systemic   distribution   injection   Myofibroblast   Dupuytren   knows--distributors   patients   studies   aforementioned   clinical   localized   concentration-effect   Xiaflex-derived   disease