Rifaximin Therapy for Patients with Irritable Bowel Syndrome without Constipation

Pimentel, Mark; Lembo, Anthony; Chey, William D.; Zakko, Salam; Ringel, Yehuda; Yu, Jing; Mareya, Shadreck M.; Shaw, Audrey L.; Bortey, Enoch; Forbes, William

doi:10.1056/nejmoa1004409

Cited by 865 publications

(729 citation statements)

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“…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.…”

Section: Introductionmentioning

confidence: 91%

“…Two identically designed, randomised, double‐blind, placebo‐controlled, phase 3 trials (TARGET 1 and TARGET 2) demonstrated that patients with non ‐ C IBS receiving rifaximin 550 mg three times daily for 2 weeks were more likely to achieve adequate relief of global IBS symptoms than those receiving placebo (40.7% vs. 31.7%, respectively; P < 0.001), as well as adequate relief of IBS–related bloating (40.2% vs. 30.3%, 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.…”

Section: Introductionmentioning

confidence: 98%

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Safety and tolerability of rifaximin for the treatment of irritable bowel syndrome without constipation: a pooled analysis of randomised, double‐blind, placebo‐controlled trials

Schoenfeld

Pimentel

Chang

et al. 2014

Aliment Pharmacol Ther

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SummaryBackgroundThe 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.ConclusionsThe 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 (ClinicalTrials.gov: NCT00269412, NCT00731679, and NCT00724126).

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Section: Introductionmentioning

confidence: 91%

Section: Introductionmentioning

confidence: 98%

Safety and tolerability of rifaximin for the treatment of irritable bowel syndrome without constipation: a pooled analysis of randomised, double‐blind, placebo‐controlled trials

Schoenfeld

Pimentel

Chang

et al. 2014

Aliment Pharmacol Ther

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“…Furthermore, rectal infusion of bacteria, particularly the Lactobacillus strains, also induces analgesic eff ects, possibly due to upregulation of μ -opioid receptors on epithelial cells rather than direct actions on GI nerves ( 24,25 ). Recent studies indicate that treatment with a nonabsorbable broad spectrum antibiotic provided relief for IBS-D patients ( 26,27 ). However, much remains to be understood regarding how changes in microbiota contribute to IBS symptoms, including details of the immunological aspects underpinning the homeostasis of the symbiotic relationship between the host and the bacteria, which bacterial strains are the most pathogenic in IBS, and how they interact with nerve endings to cause altered sensations.…”

Section: Role Of Microbiota In Ibsmentioning

confidence: 99%

Immune Activation in Irritable Bowel Syndrome: Can Neuroimmune Interactions Explain Symptoms?

Hughes

Zola

et al. 2013

American Journal of Gastroenterology

132

117

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Irritable bowel syndrome (IBS) is a functional disorder of the gastrointestinal (GI) tract characterized by pain or discomfort from the lower abdominal region, which is associated with altered bowel habit. Despite its prevalence, there is currently a lack of effective treatment options for patients. IBS has long been considered as a neurological condition resulting from alterations in the brain gut axis, but immunological alterations are increasingly reported in IBS patients, consistent with the hypothesis that there is a chronic, but low-grade, immune activation. Mediators released by immune cells act to either dampen or amplify the activity of GI nerves. Release of a number of these mediators correlates with symptoms of IBS, highlighting the importance of interactions between the immune and the nervous systems. Investigation of the role of microbiota in these interactions is in its early stages, but may provide many answers regarding the mechanisms underlying activation of the immune system in IBS. Identifying what the key changes in the GI immune system are in IBS and how these changes modulate viscerosensory nervous function is essential for the development of novel therapies for the underlying disorder.

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“…The nonsystemic antibiotic rifaximin (Xifaxan ® , Salix Pharmaceuticals, Bridgewater, NJ) was approved in 2015 by the US Food and Drug Administration for the treatment of IBS-D in adults [108]. Rifaximin 550 mg three times daily for 2 weeks has been evaluated in two phase III, identically designed, randomized, placebo-controlled IBS-D trials [109]. A significantly greater percentage of patients who received rifaximin either achieved adequate relief of global IBS symptoms for ≥2 of the first 4 weeks posttreatment or achieved adequate relief of bloating for ≥2 of the first 4 weeks posttreatment versus placebo ( Figure 2; combined population) [109].…”

Section: Antibioticsmentioning

confidence: 99%

Modulation of the gut microbiota: a focus on treatments for irritable bowel syndrome

Harris

Baffy

2017

Postgraduate Medicine

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Irritable bowel syndrome (IBS), which is characterized by recurrent abdominal pain and disordered bowel habits, is one of the most common functional bowel disorders. IBS is a substantial burden on both patient health-related quality of life and healthcare costs. Several pathophysiologic mechanisms have been postulated for the occurrence of IBS, including altered gastrointestinal motility, visceral hypersensitivity, changes in gut permeability, immune activation, gut-brain dysregulation, central nervous system dysfunction, and changes in the gut microbiota. Of note, both qualitative and quantitative differences have been observed in the gut microbiota of a population with IBS versus a healthy population. Because of the substantial interest in the gut microbiota and its role as a therapeutic target in IBS, this article provides an overview of specific interventions with the potential to modulate the gut microbiota in IBS, including elimination diets, prebiotics, probiotics, synbiotics, and nonsystemic antibiotics. Although probiotics and synbiotics are generally well tolerated, differences in the composition and concentration of different bacterial species and inclusion or exclusion of prebiotic components varies widely across studies and has prevented strong recommendations on their use in IBS. For nonsystemic antibiotics, rifaximin is indicated in the United States for the treatment of IBS with diarrhea in adults and has been shown to be efficacious and well tolerated in well-designed clinical trials. Overall, more consistent evidence is needed regarding the efficacy and safety of elimination diets, prebiotics, probiotics, and synbiotics for the treatment of patients with IBS. Furthermore, additional well-designed studies are needed that examine alterations in the gut microbiota that occur with these interventions and their potential associations with clinical symptoms of IBS. ARTICLE HISTORY

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Rifaximin Therapy for Patients with Irritable Bowel Syndrome without Constipation

Abstract: 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; ClinicalTrials.gov numbers, NCT00731679 and NCT00724126.).

Cited by 865 publications

References 20 publications

Safety and tolerability of rifaximin for the treatment of irritable bowel syndrome without constipation: a pooled analysis of randomised, double‐blind, placebo‐controlled trials

Safety and tolerability of rifaximin for the treatment of irritable bowel syndrome without constipation: a pooled analysis of randomised, double‐blind, placebo‐controlled trials

Immune Activation in Irritable Bowel Syndrome: Can Neuroimmune Interactions Explain Symptoms?

Modulation of the gut microbiota: a focus on treatments for irritable bowel syndrome

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