Antibiotic May Provide Long-Lasting Relief of Irritable Bowel Syndrome Symptoms

Laurie Barclay, MD

January 07, 2011

January 7, 2011 (UPDATED January 13, 2011) — Treatment for 2 weeks with the minimally absorbed antibiotic rifaximin provides long-lasting, significant symptom relief in patients who have irritable bowel syndrome (IBS) without constipation, according to the results of 2 randomized controlled trials reported in the January 6 issue of the New England Journal of Medicine.

"For years, the treatment options for IBS patients have been extremely limited," said lead author Mark Pimentel, MD, from Cedars-Sinai Medical Center in Los Angeles, California, in a news release. "IBS often does not respond well to treatments currently available, such as dietary changes and fiber supplements alone. With this antibiotic treatment, the patients feel better, and they continue to feel better after stopping the drug. This means that we did something to strike at the cause of the disease."

Rifaximin

Because gut flora may be important in the pathophysiology underlying IBS, the investigators evaluated rifaximin as treatment of IBS. Rifaximin is currently approved by the US Food and Drug Administration to treat travelers' diarrhea and hepatic encephalopathy.

TARGET 1 and TARGET 2 were two identically designed, phase 3, double-blind, placebo-controlled trials in patients who had IBS without constipation. Participants were randomly assigned to receive 550 mg of rifaximin or placebo, 3 times daily for 2 weeks, with follow-up for 10 additional weeks. Every week, the investigators determined the proportion of patients who had adequate relief of global IBS symptoms, which was the main study outcome, and the proportion of patients who had adequate relief of IBS-related bloating, which was the key secondary study outcome.

Self-reported symptom relief for at least 2 of the first 4 weeks after treatment was the criterion for adequate relief. Other secondary outcomes were the proportion of patients who responded to therapy, as determined by daily self-ratings of global IBS symptoms and individual symptoms of bloating, abdominal pain, and stool consistency during the 4 weeks after therapy and during the 3 months of the study.

During the first 4 weeks after treatment, adequate relief of global IBS symptoms occurred in a significantly greater proportion of patients in the rifaximin group vs the placebo group (40.8% vs 31.2%; P = .01, in TARGET 1; 40.6% vs 32.2%; P = .03, in TARGET 2; 40.7% vs 31.7%; P < .001, in both studies combined). The rifaximin group also fared better in the proportion of patients with adequate relief of bloating (39.5% vs 28.7%; P = .005, in TARGET 1; 41.0% vs 31.9%; P = .02, in TARGET 2; 40.2% vs 30.3%; P < .001, in both studies combined).

Treatment response, based on daily ratings of IBS symptoms, bloating, abdominal pain, and stool consistency, was also significantly better in the rifaximin group. Both groups had similar incidence of adverse events.

Limitations of this study include short duration of follow-up.

"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," the study authors write. "...In this short-term study, the incidence of infections was similar in the two groups, and there were no cases of C. difficile–associated diarrhea or ischemic colitis."

In an accompanying editorial, Jan Tack, MD, PhD, from the Translational Research Center for Gastrointestinal Disorders at the University of Leuven in Leuven, Belgium, refers to these as "large, high-quality, multicenter studies." Despite these advantages, however, he notes that rates of response to treatment (adequate relief) ranged between 9% and 12% more with rifaximin vs placebo, which is in the lower range of what is considered to be clinically relevant. Although not all patients have a response with rifaximin, the available data suggest that a subgroup of patients may have a substantial response.

"[T]aking into account the high prevalence of IBS in the general population, the effect that larger scale use of poorly absorbed antibiotics may have on antibiotic-resistance profiles should be taken into account," Dr. Tack writes. "Studies aimed at better identifying the patients with IBS who may have a response to rifaximin and, especially, studies that will assess the longer-term effect of rifaximin treatment are eagerly awaited. Until this information becomes available, it seems prudent to restrict the use of nonabsorbable antibiotics to patients in whom small-intestine bacterial overgrowth has been confirmed, or to single-treatment cycles in patients who have IBS without constipation and who have not had a response to currently available symptom-directed therapies."

Salix Pharmaceuticals supported this study and employs 5 of its authors. Some of the other study authors have disclosed various financial relationships with Salix Pharmaceuticals, Ironwood Pharmaceuticals, Prometheus, Ardelyx, Theravance, GlaxoSmithKline, AstraZeneca, Procter & Gamble, Ortho-McNeil, Prometheus, Pfizer, Danisco, General Mills, and/or Smart-Pill.

N Engl J Med. 2011;364:22-32, 81-82. Abstract

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