Rifaximin Improves Symptoms of Irritable Bowel Syndrome

Results of two phase 3, double-blind, placebo-controlled, randomized clinical trials [N Engl J Med. 2011;364(1):22-32] show that patients with irritable bowel syndrome (IBS) treated with rifaximin for 2 weeks had significant improvements for up to 10 weeks after completion of treatment in relief from IBS symptoms compared with patients administered placebo. Patients with IBS have recurrent symptoms of bloating, abdominal pain, and altered bowel function that often do not improve with current therapies. Some data suggest that gut flora may play a role in the pathophysiology of IBS, and small-scale studies have suggested that rifaximin, a nonsystemic, broadspectrum antibiotic with a low risk of bacterial resistance, may be effective in treating IBS symptoms. To evaluate the efficacy and safety of rifaximin to treat symptoms of IBS, investigators presented the results of 2 large-scale, multicenter studies that randomized a combined total of 1260 patients with IBS to either rifaximin 500 mg or placebo. The trials, known as TARGET 1 and TARGET 2, had identical study design and were conducted in parallel from June 2008 through August 2009. Patients eligible for inclusion had to be ≥18 years of age, had to have undergone a colonoscopic examination within the previous 2 years, and were diagnosed with and had current, unrelieved symptoms of IBS that included abdominal pain and bloating. Patients with IBS in which constipation was the predominant feature were excluded from the studies, as well as patients with a history of inflammatory bowel disease, diabetes, unstable thyroid disease, previous abdominal surgery, human immunodeficiency virus infection, and renal or hepatic disease. Patients currently taking alosetron; tegaserod; lubiprostone; warfarin; antipsychotic, antispasmodic, antidiarrheal, probiotic, or narcotic drugs; antibiotics within 14 days prior to the study; or rifaximin 60 days prior were also excluded. TARGET 1 included 623 patients, of whom 309 were randomized to receive rifaximin and 314 placebo. TARGET 2 included 627 patients, of whom 316 received rifaximin and 321 placebo. Patients received treatment 3 times daily for 2 weeks, and were then followed for another 10 weeks. The primary end point of the study was the proportion of patients with adequate relief of global IBS symptoms, and a key secondary end point was the proportion of patients with adequate relief of IBS-related bloating. The investigators defined adequate relief as relief of symptoms for at least 2 of the first 4 weeks after treatment. Based on a modified intention-to-treat analysis, the study found that significantly more patients treated with rifaximin compared with placebo had adequate relief of global IBS symptoms during the first 4 weeks after treatment in TARGET 1 (40.8% vs 31.2%; P=.01), TARGET 2 (40.6% vs 32.2%; P=.03), and in the combined trials (40.7% vs 31.7%; P<.001). Significantly more patients treated with rifaximin compared with placebo also had adequate relief of bloating in TARGET 1 (39.5% vs 28.7%; P=.005), TARGET 2 (41.0% vs 31.9%; P=.02), and in the combined trials (40.2% vs 30.3%; P<.001). No difference in the safety profile was seen between rifaximin and placebo, and the number of serious events were similar (1.6% and 2.4%, respectively), with no cases of Clostridium difficile–associated diarrhea or ischemic colitis or deaths. The investigators suggest 3 possible explanations for the antibiotic effect of rifaximin: it may reduce gut bacteria that negatively affects the host, its effect on gut flora may reduce local mucosal engagement of bacteria, or it may alter both the bacteria and the host.