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Crohn's Disease Forum » Books, Multimedia, Research & News » Antibiotic Induces Remission of Crohn's Disease in Phase 2 Trial


11-04-2010, 08:18 PM   #1
David in Seattle
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Antibiotic Induces Remission of Crohn's Disease in Phase 2 Trial

"An antibiotic currently indicated for hepatic encephalopathy and traveler's diarrhea has shown promise in the treatment of Crohn's disease (CD).

RETIC-03, a large phase 2 trial presented at the 18th Annual United European Gastroenterology Week in Barcelona, Spain, showed that rifaximin-EIR (extended intestinal release) was able to achieve clinical remission of Crohn's sequelae in up to 62% of patients out to 12 weeks, according to study investigator, Herbert Lochs, MD, from the Medical University in Innsbruck, Austria.

RETIC-03, a multicenter, multinational, randomized, double-blind, placebo-controlled study, was a comparison of 3 twice-daily doses of rifaximin-EIR (400 mg, 800 mg, and 1200 mg) and placebo in a cohort of 402 patients with active CD. The study's primary end point was remission of CD at 12-week follow-up.

Results showed that at 12 weeks, all active treatment groups achieved remission more often than placebo (P < .04), with the highest rate (62.2%) observed for the 800 mg regimen.

Response to treatment was initially dose-dependent, rising from the 400 mg to the 800 mg threshold. However, the highest dose (1200 mg) produced the least efficacy (47.5%) among the active treatment group, and the highest rate of discontinuations. Reasons for this are unclear, said Dr. Lochs. "The main adverse events tended to be mild, and the majority were gut-related, as in pain, vomiting, and diarrhea which, frankly, are very difficult to separate out from the symptoms of Crohn's itself."

Commenting on his motivation for conducting RETIC-03, Dr. Lochs said that he was trying to move away from CD treatment methods that rely on suppression of the patient's immune system. "It's not something you ideally want to do not in the long term."

In the current hypothesis for the pathogenesis of CD, he explained, there is a change in the intestinal microbiota, whereby pathogenic bacteria disrupt the gut's mucosa, which activates the immune system. Rather than inhibit the immune response, Dr. Lochs wants to attenuate the reasons for its activation.

The choice of rifaximin was based on case reports of its potential utility in CD, and the fact that it is specific to the gut. "The formulation stays in the lumen; there's no systemic effect that might lead to overall antibiotic resistance," said Dr. Lochs. In theory, this should lead to fewer adverse events than other antibiotics, he added.

"We need to do a confirmatory study, of course, but this study has shown 2 things that are different and important. First, it was possible to initiate remission with an antibiotic in active Crohn's disease, and second, this remission could be maintained." Dr. Lochs said that future studies (as yet unplanned) would address long-term maintenance of remission.

If it's so simple, why haven't we tried it before?

"The data for antibiotics [in CD] are out there, and the science makes sense," said Sunanda Kane, MD, from the Mayo Clinic in Rochester, Minnesota, and chair of the Patient Education Committee of the Crohn's and Colitis Foundation. "The problem up to now has been that no company has wanted to fund a large enough trial with the appropriate antibiotic."

Dr. Kane said that there is perhaps a different sort of motivation for such a study in the European Union, pointing out that the biologics commonly used in CD are very expensive and often not covered; in some countries, they are not even approved.

"What they are trying to do is to find an alternative to biologics that may be safer and work just as well," she observed.

Dr. Kane finds the choice of rifaximin in this study to be both prudent and just a bit ironic. "There are case studies that show efficacy, and the fact that it's so [gastrointestinal]-specific, so targeted, is great, but rifaximin is not a cheap antibiotic." Still, she admitted, the price is nowhere near that of a biologic, nor does it carry the same potential for serious adverse effects."

18th Annual United European Gastroenterology Week: Abstract 3075. Presented October 26, 2010.
11-04-2010, 09:24 PM   #2
effdee
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I've been on Xifaxin (rifaximin) before and it did help my symptoms (less bleeding, diarrhea, and pain overall) a bit, but wasn't effective enough. I noticed a difference within a week (make sure you don't miss a dose). I tolerated it pretty well, and insurance covered nearly all of it so price wasn't an issue.
11-04-2010, 10:22 PM   #3
David in Seattle
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effdee - That's interesting. The form used in the study appears to have been a specially coated variety which provides sustained intestinal release; from what I have been able to tell, "regular" Xifaxan is not this same formulation. You might have gotten better results had this been the case, but I'm not even sure it's available that way in the US.

BTW, been to the one in CA many times, but I had no idea there was a Pasadena in Maryland!
11-04-2010, 11:03 PM   #4
BLM
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Fastenating, 62% got relief and when into remission. It will be exciting to see what their follow up studies show.
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11-04-2010, 11:12 PM   #5
glum chump
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In late 2003, I was prescribed a combination of Clindamycin and Clarythromycin by a doctor who was filling in for my regular doctor. At the time, I had an abscess. After a 21-day course of these antibiotics, I went into remission for over a year and a half. Subsequently, my family doctor and my GI have been reluctant to prescribe me this combination because of concerns around C.difficile. And I have been in a flare since early 2005 with very little change.

I remain convinced that there is something to antibiotic therapy as long as the combination, dosage and length of time can be sorted out.

I remain hopeful about the results of this study, and like Bev, I'm looking forward to seeing the results from the next phase of the study.

In the meantime, maybe I can get my GI to prescribe Rifaximin to me, although my guess is that it's likely not available in Canada.
11-05-2010, 09:30 AM   #6
effdee
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effdee - That's interesting. The form used in the study appears to have been a specially coated variety which provides sustained intestinal release; from what I have been able to tell, "regular" Xifaxan is not this same formulation. You might have gotten better results had this been the case, but I'm not even sure it's available that way in the US.

BTW, been to the one in CA many times, but I had no idea there was a Pasadena in Maryland!
I might be able to check what exactly it was. My dad puts any medication that isn't being taken in the fridge. Not sure if I had any left from the last time I stopped, though.
11-05-2010, 02:33 PM   #7
karrieg
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I live in Namibia (was dx in the US though) and my doctor here also put me on antibiotics when I began having symptoms of a flare. I asked why and she said they are finding that antibiotics seem to help with Crohn's. She was uncertain as to whether I had some sort of infection or Crohn's flare but said the antibiotics should help either way but if the symptoms returned after awhile then I should have further evaluation. They did help but some symptoms have returned after a month or two.
11-06-2010, 10:29 PM   #8
MADiMarc
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I cannot wait to see what the results will be of the further trials. I have avoided antibiotics as they normally make me so ill that it is not worth it. None of the bios have worked for me so this could be my magic! Thank you so much for the information. I am going to do a search to see if I can get more information.
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11-13-2010, 05:23 PM   #9
Walt
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"An antibiotic has shown promise in the treatment of Crohn's disease (CD).
However, the highest dose (1200 mg) produced the least efficacy (47.5%) among the active treatment group,
and the highest rate of discontinuations. Reasons for this are unclear, said Dr. Lochs.
Hi David,
Thanks for posting this, it was interesting reading.
There is a glaring flaw in these study results.
The stated conclusions are misleading, offering some promise of hope to us long-sufferers...
when in fact the higher dose worked the least.

Sounds good... new and exciting research advances!
But, there's some troubling manipulation in how they present their findings.
We cannot know their motivation, perhaps they are jockeying for attention and funding?

There is no strong science behind these unfounded claims.
The way this has been handled reminds me of an ole quote:
"sub group analysis is fine, as long as you dont believe the results".

I'm eager for effective new Crohn's treatments just like the rest of us.
But this is shakey subgroup analysis at best...
...and heartbreaking misrepresentations at worst.
False hope seems cruel to me...

I asked a distinguished head CD researcher about this study, he was already aware of their claims,
shook his head in disgust, said it was unfortunate they handled the data that way,
and hinted some might call it irresponsible.

Folly to put our hopes here, I fear.
But let's keep our fingers crossed that someone makes some real CD breakthroughs...
be well,
Walt

ps YMMV
(your mileage may vary)
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11-13-2010, 09:13 PM   #10
David in Seattle
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Walt - I appreciate your concerns, but I think they are a bit overstated. I really don't see any "troubling manipulation" in how the findings were presented. Of the lower results obtained at 1200mg, Lochs correctly observes that adverse effects may be a factor, stating "...the majority were gut-related, as in pain, vomiting, and diarrhea which, frankly, are very difficult to separate out from the symptoms of Crohn's itself."

I tend to be quite cynical about human motivations in general, and having worked in pharmaceutical R&D, I can agree that $$$ is probably number 1, as it is in most all human endeavors, unfortunately. But a close 2nd in my observation is often competition and vanity. It's not uncommon for one researcher to downplay the work of others in the field for reasons not necessarily directly related to the science.

I've posted scores of full text research articles here, and I'm in no way wed to this one. Most, after all, go nowhere. But I do think it's important to keep an open mind & not jump to any conclusion, positive or negative.

I have another article involving an earlier study using rifaximin, which I will post when I get the chance.

Thanks for your observations.
11-13-2010, 10:07 PM   #11
Mountaingem
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Thanks for the interesting info! I've taken rifaximin, it worked better than Flagyl for recurrent bowel infection I was plagued with for four months.

Wouldn't it be awesome if this works out? Especially since rifaximin is alot cheaper than say, Remicade.
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11-13-2010, 11:33 PM   #12
Mark in Seattle
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I noted that there is a rifaximin trial listed for the University of Washington in Seattle. I'm thinking about it. I've never done a trial before, but it sounds relatively benign. I'm pretty naive though about the microbiata in the gut and the effects of antibiotics. I sure would like to avoid or postpone biologics or immunosuppressives. Any thoughts on the U of W trial? I saw it on clinicaltrials.gov under rifaximin. I did not see an indication of this being the extended release version. I thought it was interesting also that they indicate that it's ok to continue your current meds during the trial.

One other question - Walt - can you please clarify for those of us who may not be so sophisticated about research reports - what is the deal with your comment about "shakey subgroup analysis" and this research being misleading, unfounded, and so forth? Are you just repeating what your esteemed researcher mentioned to you, or is there something glaring in the research that you could spell out a bit more for some of the rest of us? I'd certainly appreciate it.

Anyhow David -thanks for posting this article, I find it interesting.

Last edited by Mark in Seattle; 11-13-2010 at 11:42 PM.
11-13-2010, 11:50 PM   #13
David in Seattle
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Mark - Looks intriguing. If you meet the criteria as outlined on the site you mentioned (full URL http://clinicaltrials.gov/ct2/show/N...cr=Open&rank=1 ) I would definitely consider looking into participating. Interesting that they appear to be going with a 550mg/BID dose. Please let us know what you decide & how it proceeds, and welcome to the forum!
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