2-Week Rifaximin Regimen Associated With Symptom Relief Over 12 Weeks in Nonconstipated Irritable Bowel Syndrome
The randomized, double-blind, placebo-controlled, multicenter phase III trials TARGET 1 and TARGET 2 evaluated the role of rifaximin in nonconstipated irritable bowel syndrome (IBS). A total of 1,260 patients with mild-to-moderate symptoms of nonconstipated IBS were randomly assigned to receive rifaximin 550 mg or placebo 3 times per day for 2 weeks. Patients were followed for the subsequent 10 weeks. The primary endpoint, the proportion of patients with adequate relief of weekly IBS symptoms for at least 2 of the first 4 weeks immediately following the treatment period, was significantly higher with rifaximin versus placebo in TARGET 1, TARGET 2, and the pooled data, in an intent-to-treat analysis (Table 1). Rifaximin was also associated with a significantly higher proportion of patients with IBS symptom relief and adequate relief of bloating. Patients taking rifaximin also had significantly improved daily assessments of IBS symptoms, bloating, abdominal pain, and discomfort compared to those taking placebo. The likelihood of sustained IBS symptom relief over the 3-month study period was also significantly higher with rifaximin versus placebo. The safety profile of rifaximin was similar to that of placebo.
Table 1. Responders to Adequate Relief of IBS Symptoms and IBS-related Bloating (ITT Population)
|TARGET 1 (N=623) (Rifaximin vs placebo)||TARGET 2 (N=637) (Rifaximin vs placebo)||Results of pooled data (N=1,260) (Rifaximin vs placebo)|
|Adequate relief of IBS symptoms||40.8% vs 31.2% (P=.0125)||40.6% vs 32.2% (P=.0263)||40.7% vs 31.7% (P=.0008)|
|Adequate relief of IBS-related bloating||39.5% vs 28.7% (P=.0045)||41.0% vs 31.9% (P=.0167)||40.2% vs 30.3% (P=.0002)|
Secondary Causes a Significant Factor in Patients With Presumed IBS With Short Remission After Antibiotic Therapy
The identification of small intestinal bacterial overgrowth (SIBO) by lactulose breath testing (LBT) in patients with IBS prompted the use of antibiotic therapy in IBS. This has led to the recognition of antibiotic-refractory IBS as well as a shift in tertiary care referrals of antibiotic-naive patients. In some cases, patients with abnormal LBT results have had poor responses to antibiotic therapy. To evaluate the role of alternative diagnoses in these patients, Chou and colleagues performed a chart review of patients with IBS and abnormal LBT results who were referred to a tertiary care medical center’s gastrointestinal motility program after having poor responses to antibiotics, defined as a response lasting less than 1 month. Of the 65 patients evaluated, alternative explanations for abnormal LBT results and early relapse were identified for 20 patients (30.8%). These included rectocele/pro-lapse (3 patients), small-bowel obstruction (2 patients), small-bowel diverticular disease (2 patients), intestinal malrotation (1 patient), and volvulus (1 patient). These patients were all referred for surgical treatment. Other factors contributing to SIBO and short remission periods were chronic narcotic use (3 patients), neuropathic causes (1 patient each with Addison disease, scleroderma, colonic inertia, and vagotomy from laryngeal tumor surgery), and inflammatory diseases (1 patient each with ulcerative colitis and nonsteroidal anti-inflammatory drug-induced intestinal ulceration). Unusual causes included mitochondrial myopathy, atrophic gastritis, and vitamin B12 deficiency. The researchers concluded that the increasing use of antibiotics in patients with presumed IBS will likely lead to an increase in referrals to tertiary care centers based upon a lack of response to antibiotics.