Previous Thread
Next Thread
Print Thread
Page 5 of 5 1 2 3 4 5
Re: Potential "Patch" for AS [Re: PsSpa_M_1989] #283490 08/16/19 10:23 PM
Joined: May 2019
Posts: 26
P
PainintheAS Offline OP
Registered Visitor
OP Offline
Registered Visitor
P
Joined: May 2019
Posts: 26
Originally Posted by PsSpa_M_1989
PainintheAS:

First of all, thank you for posting a very thorough topic discussion. Your self-conducted research is very valuable to others here. Because I live with someone who is a PhD in Biological Engineering and worked as a researcher and manager for a couple of Top 10 pharma companies, I know a few things from the other end of the aisle. Allow me to offer the following thoughts:

- There are plenty of research studies that noted promising outcomes in animals (usually: mice), only to turn out not to be effective in humans. Actually, even when a drug shows promise in humans with a real study, most will fail when it is put under more scrutiny. This is one of the reasons that pharma companies charge us outrageous prescription prices: They need to finance all failed drugs in the hunt of that one magic combination that will work. I'd just like to offer this view since you are choosing not to go on the available state-of-the-art treatment in the pursuit of a more experimental treatment.

- Considering the complexity and symbiosis of bacteria in our gut, in curiosity how do you determine:
a) This type of drug kills off the bacteria that do more harm than good?
b) The same bacteria won't return?
c) If yes to a) and b), the removal of bacteria will not cause other problems?
d) Are other bacteria or gut mechanisms involved in propelling spondylitis, if so, are those eliminated to?

- How are you benchmarking and following up your condition? Biomarkers? X-rays? Which efficacy does your experimental treatment show?

To me it seems that you are trying to fix the disease at the most upstream condition in the body, although not thoroughly researched or known. As you noted, the alternative is to turn off the problem downstream, with other possible side effects.

Since you started the treatment, which improvements have you noticed?

Thanks,
PsSpa_M_1989


Hey, really great reply. I plan to follow up with x-ray results and other metrics in the near future! However, there are some inaccuracies in what you've said. I mentioned some of these things before but maybe it just isn't clear because I write a lot, lol. I'll reply to each point.

1)
IBS is now clearly known to be marked by an imbalance in the intestinal flora. This imbalance has certain characteristic traits in certain diseases. Rifaximin IS APPROVED for IBS treatment. I have the same intestinal floral imbalance (skewed firmicutes to bacteroidetes ratio) as the rats transfected with HLA-B27. Rifaximin also immediately made my "sensation" of stress (which is related to cytokines and interleukins...you can read any recent paper on major depressive disorder or schizophrenia and find that the leakiness in the blood-brain barrier, versus the AS disease leakiness in the gut, exists. The same cytokines that cause inflammation in AS sufferers are the same cytokines that cause issues for those with these mental conditions.) This is because cytokines are responsible for both groups of people inducing a "stress/inflammation" response. You will find that many of the symptoms of "lethargy, lack of motivation, and exhaustion" can occur in severe cases of MDD. Why? They are both related to cytokine expression in some way.

2)
The bacteria CAN return. This is why it's important to try and remove, then outcompete them with proper strains that don't elicit an immune response in me (HLA-B27 genetics must be considered here.) This also explains why when I eat certain foods that are healthy for others (like certain fermented foods) I am permanently screwed after. The bacteria compete with the ones that I have so strongly that they start to take over. I will then NOT heal without antimicrobial intervention. This is the same thing that happened to me when I visited Mexico. My friend and I ate the same things, but I got sick because a) less mucosal membrane protection and b) far less diversity in my microbiota to handle the offense and outcompete the invader. It turned out what I was infected with happened to also be pathogenic for pretty much anyone but I could not fend it off.

3)
I mentioned studies where similar drugs were used IN HUMANS with great positive effect. Rifaximin is just one choice, there are others I mentioned that were tested in humans that brought down chemokine markers. I posted the studies here. Some of the studies have even stated directly that "it is now commonly accepted in research that AS is a disease of the gut (or periodontal.)" Those studies are posted here too. Whether or not every drug works in humans that works in mice is not really up for debate to me. I took Rifaximin, I immediately felt the "calm" that came with reduced cytokine expression. Did I test for it? No. I don't have a readily available method to do that without great expense. I can also go take a bunch of the other medications I've listed (and I am actually going to do that for experimental understanding and to try and address my Reactive Arthritis problem that accompanies a spectrum of issues I have related to HLA-B27 genetics.) However, I can tell you without a doubt, DRASTIC improvement using Rifaximin. I can digest better, I have less pain, and my lethargy and extreme sweating with minimal exertion have reduced (all signs of less stress response.) I will soon try to seek approval for Rifamycin as it has an effect that I think is necessary that Rifaximin doesn't, which is it can help heal intestinal cells in addition to the upregulating of tight-junction proteins.

4)
If there are other mechanisms of AS that Rifaximin/antibiotics won't treat (which there may very well be,) my research hasn't indicated much in the way of this. I still scour once a week to find out. The most CUTTING EDGE (2017-2019) research indicates it is a disease of intestinal permeability (makes sense, invaders making it into the bloodstream, just as they would in the mouth) and bacterial imbalance, either mediated by genetics or some offending event. Every member I spoke to here in the beginning of my post mentioned that their disease started after some "event" that was either pathogen from travel/food or periodontal in nature.

5)
The state-of-the-art treatments currently available clearly have side-effects that include death. Not really willing to risk infection, cancer, or death. Your body NEEDS to communicate via chemokines. Blocking them is unwise. I guarantee within 10 years, this approach currently being taken will be out the door. Doctors still prescribe NSAIDs to people with AS. My AS started becoming drastically worse after 2-3 days of taking a pain-reliever. I told the doctor prescribing me it that this would be the result and he said not to worry. The state of the art treatments START with NSAIDs and then work their way up to biologics. If a doctor can hand me something that is going to burn my intestinal lining away, I think I would rather take an approach that builds it back up, or brings things back to balance (which is what tests using Rifaximin have been shown to do in HUMAN IBS patients, not just rats. This is why it is approved for HUMANS.)

6)
Pharmacokinetics can affect the way the same drug operates in the same person. Which fillers are used varies from generic to a brand name and this causes people to have altered uptake of the medicine. Requirements for a generic medication to be okayed by the regulating agencies require the blood concentration to be something like 40% similar within a certain timeframe. I can't remember the exactly metric but remember reading it and thinking that this is LAUGHABLY ridiculous as the difference between the generic absorption and the brand name can be wildly different. So much so that the dose for one person in one drug could be completely different than what is required in the bloodstream. It's sheer madness to promote money-making opportunities for other companies to produce generics. On top of that, the reason pharmaceutical companies can charge so much for their drug is not quite as simple reasons as you claim. They pay other companies to "not compete" and create a generic equivalent. This can cost taxpayers up to 3.5 billion a year. Have a read about it (and many other lovely practices employed) here. LINK

--------

What's current in research labs is rarely what's current in a doctors office. Doctors are usually very behind and dogmatic. They stick to what they were taught in school when that was cutting-edge and don't keep up as often as they should. I've met a few doctors that do keep up and my goodness it is so much more relieving to talk to someone who continually hones their craft. Big pharma also has to charge a lot of money for other reasons. They line the pockets of specific doctors who tout their drug, versus other competing drugs, on the market. Here's JUST ONE example (Link). Many doctors have written articles about their guilt being so high that they had to start turning down these companies because the things they were told to regurgitate during medical conferences were actually quite questionable. I read a few articles to this tune. I've also been mistreated/misdiagnosed by doctors MULTIPLE times, simply because they didn't want to hear me out. This has to do with the general psychology of professional thinking that someone else can't have insight or perspective that might be informative. It is an issue with ego and I began to get tired of it causing me harm. I sought to help myself because I felt I was equipped enough to do so. I would like to note that my self-treatment has resulted in greater healing and benefit than ANYTHING a doctor has ever given to me, except the one I mentioned who "keeps up." That woman is truly a healer/doctor and "practices medicine" IMHO. Many doctors take the Hippocratic Oath to do no harm. But if you look at the number of misdiagnosis and deaths due to medicines and their side effects, coupled with their pockets being lined for pushing certain drugs, you can see that there is just really a lot of hypocrisy going around.

Now that I am feeling better enough to get back out in the world, I have applied for a Master's Degree in Machine Learning and Data Science, with an emphasis on early detection and prevention of disease. It is a growing movement and I plan to make changes and give alternatives to people so that they need to enter this wheelhouse of "take this drug you'll be ok." I also plan to be involved in genomics and microbiome analysis. They've already designed certain strains of bacteria to treat arthritis and other autoimmune conditions because the bacteria produce IL-10, a Th2 cytokine which promotes immune regulation and not inflammation. Other research has been done for arthritis in gene editing cells to produce anti-inflammatory molecules when stressed instead of the normal inflammatory molecules. These approaches will be vastly superior to taking drugs.

Re: Potential "Patch" for AS [Re: PainintheAS] #283493 08/17/19 06:29 AM
Joined: Aug 2019
Posts: 3
PsSpa_M_1989 Online
Registered Visitor
Online
Registered Visitor
Joined: Aug 2019
Posts: 3
Thanks again, for a very thorough response. I appreciate the opportunity to share thoughts with you and to tap into your knowledge of current research.

Originally Posted by PainintheAS
1)
IBS is now clearly known to be marked by an imbalance in the intestinal flora. This imbalance has certain characteristic traits in certain diseases. Rifaximin IS APPROVED for IBS treatment. I have the same intestinal floral imbalance (skewed firmicutes to bacteroidetes ratio) as the rats transfected with HLA-B27. Rifaximin also immediately made my "sensation" of stress (which is related to cytokines and interleukins...you can read any recent paper on major depressive disorder or schizophrenia and find that the leakiness in the blood-brain barrier, versus the AS disease leakiness in the gut, exists. The same cytokines that cause inflammation in AS sufferers are the same cytokines that cause issues for those with these mental conditions.) This is because cytokines are responsible for both groups of people inducing a "stress/inflammation" response. You will find that many of the symptoms of "lethargy, lack of motivation, and exhaustion" can occur in severe cases of MDD. Why? They are both related to cytokine expression in some way.


Did you find that the stress relief you experienced with Rifaximin, was similar to that of dietary intervention? Before I started a TNF-alpha inhibitor, I tried the Autoimmune Protocol for 30 days. My stressors were definetely severely hampered during this diet. The day I switched back to a standard diet I had a cup of coffee and a pastry in the morning (bike to work day..). Within a minute my body felt like it was going through a stress reaction, very strange feeling after a month of plants, salmon, shrimps, chicken, cassava root/coconut flour, coconut milk, tons of turmeric/ginger/garlic, and berries/occassional orange.

My ESR decreased from 32 to 30 and my CRP decreased from 22 mg/dL to 9 mg/dL with 30 days of the AIP-diet. Not back to normal ranges but possibly supporting your conclusion that harmful bacteria go into hibernation/starvation with diet-only are still able to proliferate (albeit with less intensity). I also don't know if my data set is sufficient to make any conclusions about this, however it is better than nothing.

I intend to post a thread within the next few months about my experience with NSAID, diets, biologics, chinese herbs (had no effect, even though many of them are supposed to suppress certain bacteria in the gut and bind to TNF-alpha, COX, various interleukins, etc. according to studies in animals: link: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4003708/), after about 10 months of trial-and-error since my diagnosis. My primary benchmark is ESR/CRP since they were both elevated at diagnosis and fluctuated with dietary interventions and medications.

Originally Posted by PainintheAS
2)
The bacteria CAN return. This is why it's important to try and remove, then outcompete them with proper strains that don't elicit an immune response in me (HLA-B27 genetics must be considered here.) This also explains why when I eat certain foods that are healthy for others (like certain fermented foods) I am permanently screwed after. The bacteria compete with the ones that I have so strongly that they start to take over. I will then NOT heal without antimicrobial intervention. This is the same thing that happened to me when I visited Mexico. My friend and I ate the same things, but I got sick because a) less mucosal membrane protection and b) far less diversity in my microbiota to handle the offense and outcompete the invader. It turned out what I was infected with happened to also be pathogenic for pretty much anyone but I could not fend it off.


To me, it seems a big challenge is how to identify the maintenance phase after you get rid of the bacteria? Given individual response to bacteria composition.

Originally Posted by PainintheAS
3)
I mentioned studies where similar drugs were used IN HUMANS with great positive effect. Rifaximin is just one choice, there are others I mentioned that were tested in humans that brought down chemokine markers. I posted the studies here. Some of the studies have even stated directly that "it is now commonly accepted in research that AS is a disease of the gut (or periodontal.)" Those studies are posted here too. Whether or not every drug works in humans that works in mice is not really up for debate to me. I took Rifaximin, I immediately felt the "calm" that came with reduced cytokine expression. Did I test for it? No. I don't have a readily available method to do that without great expense. I can also go take a bunch of the other medications I've listed (and I am actually going to do that for experimental understanding and to try and address my Reactive Arthritis problem that accompanies a spectrum of issues I have related to HLA-B27 genetics.) However, I can tell you without a doubt, DRASTIC improvement using Rifaximin. I can digest better, I have less pain, and my lethargy and extreme sweating with minimal exertion have reduced (all signs of less stress response.) I will soon try to seek approval for Rifamycin as it has an effect that I think is necessary that Rifaximin doesn't, which is it can help heal intestinal cells in addition to the upregulating of tight-junction proteins.

4)
If there are other mechanisms of AS that Rifaximin/antibiotics won't treat (which there may very well be,) my research hasn't indicated much in the way of this. I still scour once a week to find out. The most CUTTING EDGE (2017-2019) research indicates it is a disease of intestinal permeability (makes sense, invaders making it into the bloodstream, just as they would in the mouth) and bacterial imbalance, either mediated by genetics or some offending event. Every member I spoke to here in the beginning of my post mentioned that their disease started after some "event" that was either pathogen from travel/food or periodontal in nature.


What impact has Rifaximin had on your AS symptoms? If you have elevated ESR/CRP, that is a good way to keep tabs on your acute phase inflammation. Preferrably before and after Rifaximin.

My diagnosis is "axial psoriatic arhtritis" (axPsa, aka psoriatic spondylitis). I am HLA-B27 negative but I suspect I have the HLA-C06 allele since my psoriasis broke out when I was a child and my arthritis presented 12-15 years after that. I am not able to trace my psoriasis nor my psoriatic arhritis to a certain infection; however, my mother said that one of my early doctors believed my psoriasis was triggered by a strep throat. Psoriatic arthritis could be a latent feature of the same disease, the same way as some with autoimmune disorders have latent leukemia, lymphoma, etc. As a child I also had many other infections (including issues with # of white blood cells), apparently uncommonly many according to my mother, even for a child. My immune system appears to have overcompensated for that later in life, as I didn't have fever or a sick day in well over a decade. I'm 30 now.

Unfortunately, axPsa is much less known than both AS and pPsa, since only 5% of Psa patients present with this condition. In fact, researchers are only recently showing interest in studying axPsa. Consequently, a research agenda is still being debated by the authorities on the subejct:

https://ard.bmj.com/content/76/4/701
https://journals.lww.com/co-rheumat...dylitis_or_ankylosing_spondylitis.3.aspx

A part of the issue is that axPsa and AS appear to be on a spectrum. I.e., it may not be entirely clear whether someone has axial psoriatic arthritis or ankylosing spondylitis with psoriasis. When I look at the diagnostic criteria, I find myself somewhere in between. My age of onset was earlier than axPsa but later than AS. I am HLA-B27 negative but have sclerosis of my sacroiliac joint.

The reason I write all this, is that I wonder if axPsa and AS have the same causes? Did you come across anything to that effect in your research, or something that could inform my condition?

Originally Posted by PainintheAS
5)
The state-of-the-art treatments currently available clearly have side-effects that include death. Not really willing to risk infection, cancer, or death. Your body NEEDS to communicate via chemokines. Blocking them is unwise. I guarantee within 10 years, this approach currently being taken will be out the door. Doctors still prescribe NSAIDs to people with AS. My AS started becoming drastically worse after 2-3 days of taking a pain-reliever. I told the doctor prescribing me it that this would be the result and he said not to worry. The state of the art treatments START with NSAIDs and then work their way up to biologics. If a doctor can hand me something that is going to burn my intestinal lining away, I think I would rather take an approach that builds it back up, or brings things back to balance (which is what tests using Rifaximin have been shown to do in HUMAN IBS patients, not just rats. This is why it is approved for HUMANS.)

6)
Pharmacokinetics can affect the way the same drug operates in the same person. Which fillers are used varies from generic to a brand name and this causes people to have altered uptake of the medicine. Requirements for a generic medication to be okayed by the regulating agencies require the blood concentration to be something like 40% similar within a certain timeframe. I can't remember the exactly metric but remember reading it and thinking that this is LAUGHABLY ridiculous as the difference between the generic absorption and the brand name can be wildly different. So much so that the dose for one person in one drug could be completely different than what is required in the bloodstream. It's sheer madness to promote money-making opportunities for other companies to produce generics. On top of that, the reason pharmaceutical companies can charge so much for their drug is not quite as simple reasons as you claim. They pay other companies to "not compete" and create a generic equivalent. This can cost taxpayers up to 3.5 billion a year. Have a read about it (and many other lovely practices employed) here. LINK


Personally, I saw more effect with AIP than NSAID. So I agree that NSAID is not state-of-the-art. Biologics still to be determined for me but my biomarkers returned to normal within 5 weeks. Some studies suggest that biologics slow down and sometimes reverses mSASSS.

Regarding big pharma - it is a whole other discussion. It tends to become somewhat black/white. I have seen them from the other side though, they do good things too. America just has a stupid health care system that exacerbates businesses ability to take advantage of people.

I went through almost a half-year argument with myself whether I was going to start TNF-alpha inhibitors or not. The chance of getting a serious infection sometime during long-term treatment with biologics is very likely. It is almost a certain outcome if you look at the statistics. Cancer seems less certain, from the published data this far. However, these risks also exist in placebo groups to a surprising degree. As patients with automimmune diseases, we are already at elevated risk for infections and cancers. Biologics may lower another important risk factor: Cardiovascular events, a leading cause of premature death for individuals with chronic inflammation.

Here is the article library I used when deciding for biologics and which eventually helped me convince to start this treatment:

PSORIATIC ARTHRITIS MORTALITY ARTICLES

https://academic.oup.com/rheumatology/article/56/6/907/2965335
http://www.jrheum.org/content/37/9/1898
https://acrabstracts.org/abstract/mortality-rates-and-causes-in-psoriatic-arthritis-patients/
https://www.ncbi.nlm.nih.gov/pubmed/29947129
https://ard.bmj.com/content/73/1/149
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3883139/
https://ard.bmj.com/content/64/suppl_2/ii14
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4133459/
https://mauiderm.com/update-on-psoriatic-arthritis-and-the-focus-on-new-treatments/
https://academic.oup.com/rheumatology/article/58/1/80/5077390
https://synapse.koreamed.org/DOIx.php?id=10.4078/jrd.2018.25.3.197&vmode=PUBREADER

VACCINATIONS

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4080407/
http://www.ibdclinic.ca/treatment/m...at-checks-will-i-need-before-i-start-it/
https://www.uspharmacist.com/articl...ng-disease-modifying-antirheumatic-drugs
https://ard.bmj.com/content/76/2/414

PSORIATIC ARTHRITIS HUMIRA SIDE EFFECTS / LONG TERM STUDIES EFFECTIVENESS

https://clinicaltrials.gov/ct2/show/results/NCT01111240
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5574748/
https://www.centerforbiosimilars.co...es-for-patients-with-psoriatic-arthritis

PSORIATIC ARHTRITIS TREATMENT

https://journals.sagepub.com/doi/10.1177/2475530318812244

COMBORBIDITES

https://www.jmcp.org/doi/full/10.18553/jmcp.2018.17421

NON-PUBLIC ARTICLES

Cardiovascular morbidity and mortality Liew 2019
Mortality and causes of death in 398 patients admitted to hospital with ankylosing spondylitis Lehtinen 1993
Early psoriatic arthritis: short symptom duration, male gender, and preserved physical functioning at presentation predict favourable outcome at 5-year follow-up (Theander 2012)

Originally Posted by PainintheAS
What's current in research labs is rarely what's current in a doctors office. Doctors are usually very behind and dogmatic. They stick to what they were taught in school when that was cutting-edge and don't keep up as often as they should. I've met a few doctors that do keep up and my goodness it is so much more relieving to talk to someone who continually hones their craft. Big pharma also has to charge a lot of money for other reasons. They line the pockets of specific doctors who tout their drug, versus other competing drugs, on the market. Here's JUST ONE example


In my opinion, yes and no. My rheumatologist is out of med school within the last 10 years (likely speaks to your point) and she is somewhat open to dietary interventions. I will ask her about your hypothesis. I think most doctors try to keep up by way of conferences and collegial work. Many may not do in-depth research but most are at least committed to their patients.

My main critique of doctors are their lack of imagination and foresight. They always react to symptoms and rarely seem to bother with preventive care. For all the dermatologists I met over the last 15 years, no one ever told me that I am at higher risk for cardiovascular problems and cancers, nor that diet can be very helpful. All I learned about my risk factors and dietary benefits, I learned myself. If I knew this I would have adjusted my S-A-D diet much earlier than I did!

Originally Posted by PainintheAS
Many doctors have written articles about their guilt being so high that they had to start turning down these companies because the things they were told to regurgitate during medical conferences were actually quite questionable.


Yes this most likely influences which medication they prescribe too. I.e. if AbbVie takes you out for trips and fancy dinners you are probably more likely to advocate Humira over Enbrel, Cimzia or Cosentyx.

Originally Posted by PainintheAS
I read a few articles to this tune. I've also been mistreated/misdiagnosed by doctors MULTIPLE times, simply because they didn't want to hear me out. This has to do with the general psychology of professional thinking that someone else can't have insight or perspective that might be informative. It is an issue with ego and I began to get tired of it causing me harm. I sought to help myself because I felt I was equipped enough to do so. I would like to note that my self-treatment has resulted in greater healing and benefit than ANYTHING a doctor has ever given to me, except the one I mentioned who "keeps up." That woman is truly a healer/doctor and "practices medicine" IMHO. Many doctors take the Hippocratic Oath to do no harm. But if you look at the number of misdiagnosis and deaths due to medicines and their side effects, coupled with their pockets being lined for pushing certain drugs, you can see that there is just really a lot of hypocrisy going around.


Misdiagnosis is definitely a problem. Also: lack of knowledge/insight. My GP didn't seem to know psoriatic arthritis was a disease, when I presented with psoriasis and stiff neck. She relied on specialists to make the diagnosis. The experiences you had could also be a problem of hiearchy; the doctor is supposed to be an authority and if the patient starts asking uncomfortable questions that redefines the hiearchy, it becomes threatening for the person who values to uphold the authority. Curious patients should not be an issue for doctors who care more for the patients' wellbeing than their doctor's license.

Originally Posted by PainintheAS
Now that I am feeling better enough to get back out in the world, I have applied for a Master's Degree in Machine Learning and Data Science, with an emphasis on early detection and prevention of disease. It is a growing movement and I plan to make changes and give alternatives to people so that they need to enter this wheelhouse of "take this drug you'll be ok." I also plan to be involved in genomics and microbiome analysis. They've already designed certain strains of bacteria to treat arthritis and other autoimmune conditions because the bacteria produce IL-10, a Th2 cytokine which promotes immune regulation and not inflammation. Other research has been done for arthritis in gene editing cells to produce anti-inflammatory molecules when stressed instead of the normal inflammatory molecules. These approaches will be vastly superior to taking drugs.


Good job and good luck. Remember that drugs are supposed to make us feel better and manage our conditions. We all have to make our decisions on how to get better.

Last edited by PsSpa_M_1989; 08/17/19 06:41 AM.

Background: 30 yr old male
Symptoms: Ps (scalp, elbows, knees) since 2000; PsSpa (neck, sacroiliac joint) since 2015
Dx: Osteoarthritis Aug, 2017; PsSpa Nov, 2018
Treatment: Meloxicam, Nov 2018-Jan 2019; Naproxen, Jan 2019-Jun 2019; Humira, Jun 2019-Present
Page 5 of 5 1 2 3 4 5

Moderated by  ElinAslanyan, RyanMiyamoto 

Powered by UBB.threads™ PHP Forum Software 7.7.3