麻豆传媒

Rifaximin (Xifaxan) is approved for the treatment of adults with irritable bowel syndrome plus diarrhea and has demonstrated efficacy versus placebo for the improvement of abdominal and bowel symptoms, including fecal urgency and stool consistency.

A post-hoc analysis of two phase III trials was conducted to determine if rifaximin could simultaneously improve symptoms of both fecal urgency and loose/watery stool consistency. The findings were presented at the American College of Gastroenterology annual meeting.

In this exclusive 麻豆传媒 video, lead investigator Brooks D. Cash, MD, of the University of Texas Health Science Center at Houston, discusses the study.

Following is a transcript of his remarks:

This study was poster number D0266, and it had to do with an alternative analysis of some data from the phase III trials of rifaximin. This is also known as Xifaxan. This is a drug that's FDA approved for the treatment of IBS with diarrhea. It's a very poorly absorbed, almost non-absorbed, antibiotic that we believe is affecting the microbiome and exerting in effect to improve symptoms in IBS.

And so what we did was a post-hoc analysis of two large studies that are called the TARGET 1 and the TARGET 2 studies. And those were the original two phase III trials that were done to get this drug FDA approved. A subsequent third trial was done called the TARGET 3 trial, and that was actually specifically looking at repeat treatment.

So with these two studies, what we analyzed was an alternative endpoint for response. So what the FDA requires is, in 2022 for a response for an IBS study, is what was called a composite endpoint responder definition. And that is somebody who responds not only with an improvement in abdominal pain by at least 30%, but also a substantive improvement in their stool form, whether it's constipation or diarrhea, depending on what you're treating. And that has to be at the same time, in the same week or the same day, and it needs to be typically for at least 50% of the days in the trial. So that's the composite endpoint responder definition that the FDA requires as their primary outcome.

Now, when these two studies were done, that was actually before the era of this composite responder analysis, or definition. So they looked at Global IBS Improvement [Scale] and they also looked at bloating as their primary outcomes. So what we did in this study was we went back, we took the data that had been collected, and we basically recreated a different outcome measure. And that was another composite responder definition. But in this case, we didn't look at abdominal pain, we looked at abdominal or fecal urgency, which is a very bothersome symptom and kind of speaks to itself in terms of what it describes. But that fear of having an incontinence episode is really debilitating for some patients. And it's thought to be a marker of IBS severity.

So we created a new post-hoc composite responder definition that included an improvement in stool form at the same time that patients had -- this is in the same day -- with regards to their fecal urgency. And we looked at this both in the short term after therapy, as well as what we call sustained responders, or long term.

And what we found was that nearly half the patients who were treated with rifaximin in each of these trials met the definition for composite bowel symptom responders, so improvement in stool form, as well as fecal urgency, and they also met the responder definition for sustained response. And that was defined as maintaining that response for at least 3 out of an additional 6 weeks of analysis after treatment.

And we found that these differences were statistically significantly improved or superior to placebo, about an 8% to 9% difference between those two therapies, and you can calculate your number to treat if you wanted to from that. So that's the upstart of our study, basically looking at stool form and fecal urgency.

The importance of this to clinicians is that this is an important clinical feature to assess in patients and really get that history of whether patients have had fecal incontinence. It's not something that a lot of patients like to admit because it's embarrassing, but you can imagine how devastating it is in a social or even a work scenario to have an episode of fecal incontinence. So asking about that urgency is important, and what we showed was that rifaximin can improve that specific symptom, along with the stool form in patients, just like it's been shown to do for pain, as well as bloating, and other features and symptoms of irritable bowel syndrome with diarrhea.

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