Rifaximin Therapy for Patients with Irritable Bowel Syndrome without Constipation

Cedars-Sinai Medical Center, Los Angeles, USA.
New England Journal of Medicine (Impact Factor: 55.87). 01/2011; 364(1):22-32. DOI: 10.1056/NEJMoa1004409
Source: PubMed


Evidence suggests that gut flora may play an important role in the pathophysiology of the irritable bowel syndrome (IBS). We evaluated rifaximin, a minimally absorbed antibiotic, as treatment for IBS.
In two identically designed, phase 3, double-blind, placebo-controlled trials (TARGET 1 and TARGET 2), patients who had IBS without constipation were randomly assigned to either rifaximin at a dose of 550 mg or placebo, three times daily for 2 weeks, and were followed for an additional 10 weeks. The primary end point, the proportion of patients who had adequate relief of global IBS symptoms, and the key secondary end point, the proportion of patients who had adequate relief of IBS-related bloating, were assessed weekly. Adequate relief was defined as self-reported relief of symptoms for at least 2 of the first 4 weeks after treatment. Other secondary end points included the percentage of patients who had a response to treatment as assessed by daily self-ratings of global IBS symptoms and individual symptoms of bloating, abdominal pain, and stool consistency during the 4 weeks after treatment and during the entire 3 months of the study.
Significantly more patients in the rifaximin group than in the placebo group had adequate relief of global IBS symptoms during the first 4 weeks after treatment (40.8% vs. 31.2%, P=0.01, in TARGET 1; 40.6% vs. 32.2%, P=0.03, in TARGET 2; 40.7% vs. 31.7%, P<0.001, in the two studies combined). Similarly, more patients in the rifaximin group than in the placebo group had adequate relief of bloating (39.5% vs. 28.7%, P=0.005, in TARGET 1; 41.0% vs. 31.9%, P=0.02, in TARGET 2; 40.2% vs. 30.3%, P<0.001, in the two studies combined). In addition, significantly more patients in the rifaximin group had a response to treatment as assessed by daily ratings of IBS symptoms, bloating, abdominal pain, and stool consistency. The incidence of adverse events was similar in the two groups.
Among patients who had IBS without constipation, treatment with rifaximin for 2 weeks provided significant relief of IBS symptoms, bloating, abdominal pain, and loose or watery stools. (Funded by Salix Pharmaceuticals; numbers, NCT00731679 and NCT00724126.).

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Available from: William Chey, Dec 02, 2014
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    • "P < 0.001) during ≥2 of the first 4 weeks post‐treatment compared with placebo.9 Furthermore, a significantly greater percentage of patients treated with rifaximin experienced adequate relief of global symptoms of IBS throughout the 12‐week studies (2 weeks of treatment and 10 weeks of follow‐up).9 A phase 2b dose‐ranging study also demonstrated efficacy of rifaximin vs. placebo in patients with non‐C IBS.10 "
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    ABSTRACT: Background The efficacy of rifaximin, a nonsystemic, gut-targeted antibiotic for reducing non–constipation-predominant irritable bowel syndrome (non-C IBS) symptoms, has been demonstrated in one phase 2b and two phase 3 randomised, double-blind, placebo-controlled trials, but detailed data about rifaximin safety and tolerability during treatment and subsequent follow-up periods are lacking.AimTo assess and determine the frequency of rifaximin and placebo adverse events (AEs) in phase 2b and phase 3 non-C IBS trials.MethodsA post hoc pooled safety analysis of the phase 2b (rifaximin 275, 550, and 1100 mg twice daily for 2 weeks; 550 mg twice daily for 4 weeks) and phase 3 (rifaximin 550 mg three times daily for 2 weeks) studies was performed. Data on treatment and post-treatment AEs were collected. Patients were followed up for 12 weeks and 10 weeks post-treatment in the phase 2b and phase 3 trials, respectively.ResultsPatients receiving rifaximin (n = 1103) and placebo (n = 829) had a similar incidence of drug-related AEs (12.1% vs. 10.7%), serious AEs (1.5% vs. 2.2%), drug-related AEs resulting in study discontinuation (0.8% vs. 0.8%), gastrointestinal-associated AEs (12.2% vs. 12.2%) and infection-associated AEs (8.5% vs. 9.5%). There were no cases of Clostridium difficile colitis or deaths.Conclusions The safety and tolerability profile of rifaximin during treatment and post-treatment was comparable to placebo. Future research should define the safety and tolerability profile, including risk of C. difficile colitis and microbial antibiotic resistance, with repeated courses of rifaximin in patients with non—constipation-predominant irritable bowel syndrome ( NCT00269412, NCT00731679, and NCT00724126).
    Full-text · Article · Apr 2014 · Alimentary Pharmacology & Therapeutics
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    • "It should also be recognised that differences between studies may be due to the causative microorganisms or imbalances differing between IBS subtypes. Regardless, a bacterial role in IBS onset would seem to be clear, as further evidenced by the disease's response to antibiotic therapy [33] and differential expression levels of Toll-like receptors in colonic biopsies of patients with IBS [34] "
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    ABSTRACT: The human gut microbiota comprises approximately 100 trillion microbial cells and has a significant effect on many aspects of human physiology including metabolism, nutrient absorption and immune function. Disruption of this population has been implicated in many conditions and diseases, including examples such as obesity, inflammatory bowel disease and colorectal cancer that are highlighted in this review. A logical extension of these observations suggests that the manipulation of the gut microbiota can be employed to prevent or treat these conditions. Thus, here we highlight a variety of options, including the use of changes in diet (including the use of prebiotics), antimicrobial-based intervention, probiotics and faecal microbiota transplantation, and discuss their relative merits with respect to modulating the intestinal community in a beneficial way.
    Full-text · Article · Mar 2014 · FEBS letters
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    • "However, currently, such methods have limited practicality as a routine clinical biomarker as they are resource and labour intensive (Arumugam et al. 2011). Pimentel et al. (2011) have reported the combined results of two phase III trials evaluating the utility of the non-absorbable antibiotic rifaximin in non-constipated IBS, demonstrating a small but significant improvement of global symptoms, bloating, abdominal pain, and loose or watery stools. In IBD, preliminary data also suggest that rifaximin may offer a therapeutic benefit in inducing and maintaining remission (Guslandi, 2011). "
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    ABSTRACT: Common human experience shows that stress and anxiety may modulate gut function. Such observations have been combined with an increasing experimental evidence base have culminated in the concept of the brain-gut axis. Nevertheless, it has not been until recently that the gut and its attendant components, have been considered to influence higher cerebral function and behaviour per se. Moreover, the proposal that the gut and the bacteria contained therein (collectively referred to as the microbiota) can modulate mood and behaviours, has an increasing body of supporting evidence, albeit largely derived from animal studies. The gut microbiota is a dynamic and diverse ecosystem and forms a symbiotic relationship with the host. Herein we describe the components of the gut microbiota and mechanisms by which it can influence neural development, complex behaviours and nociception. Furthermore, we propose the novel concept of a ‘state of gut’ rather than a state of mind, particularly in relation to functional bowel disorders. Finally, we address the exciting possibility that the gut microbiota may offer a novel area of therapeutic intervention across a diverse array of both affective and GI disorders.This article is protected by copyright. All rights reserved
    Full-text · Article · Mar 2014 · The Journal of Physiology
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