There is no delicate way to put it: managing irritable bowel syndrome (IBS) has historically been a pain in the rear end. Few effective treatment options exist, and developing new therapies has proven challenging.
A study by Pimental et al published in this week’s NEJM, however, suggests there may be a new option for patients with IBS: rifaximin, a poorly absorbed antibiotic. The authors report findings from two large double-blind placebo-controlled trials (TARGET 1 & 2) that together enrolled more than 1,250 patients with non-constipation IBS in the United States and Canada. Half of the enrollees received 2 weeks of treatment with rifaximin 3 times daily; the other half received placebos. All enrollees were then followed for an additional 10 weeks.
The primary endpoint of the study was the percentage of patients reporting adequate relief of global symptoms of IBS for at least 2 of the first 4 weeks following treatment. This was evaluated using a weekly yes-or-no question during the first 4 weeks of follow-up. The authors indicate that a significantly higher proportion of patients who received rifaximin reported adequate relief during this period as compared with patients who received placebo (41% vs. 32%, p<0.001). Moreover, the observed difference between the two groups remained statistically significant when the entire 10-week period of follow-up was analyzed.
The secondary endpoint evaluated was adequate relief of bloating – often considered one of the most challenging symptoms of IBS – during the first 4 weeks of follow-up. Again, a significantly higher proportion of patients in the rifaximin treatment arm reported adequate relief, as compared with patients in the control arm (40% vs. 30%, p<0.001). The difference remained statistically significant when evaluating the entire 10-week follow-up period.
What do these study findings potentially mean for the management of IBS? In an accompanying editorial, Dr. Jan Tack of the University of Leuven in Belgium writes, “With 3 studies confirming efficacy after a short-term treatment and a relatively short follow-up period, rifaximin has the potential to provide a welcome addition to the limited armamentarium of agents available to treat IBS.”
There is certainly reason for optimism: rifaximin seemed to offer relief over a sustained period after just a short treatment course. And rifaximin has been shown to have a favorable safety and side effect profile; it is frequently used to prevent or treat traveler’s diarrhea.
On the other hand, the TARGET trial results suggest that the benefits associated with using rifaximin may be modest for IBS patients. The therapeutic gain relative to placebo was around 10%; this falls on the lower end of the spectrum of what is considered clinically relevant. Critics might also question the prudence of using antibiotics to treat a chronic disease like IBS. It is unclear whether rifaximin would continue to effectively relieve the symptoms of IBS with recurrent use. And there is always the concern of inducing antibiotic resistance.
NEJM deputy editor Dr. Mary Beth Hamel commented, “The TARGET trials examined a novel treatment for a common and difficult to treat chronic disease. The results are promising but longer studies will be needed to determine the risks and benefits of rifaximin for irritable bowel disease.”
It remains to be seen whether rifaximin has hit the bull’s-eye of IBS treatment. But for now, at the very least, the results of the TARGET trials promise to move this challenging area of research in an exciting direction.
How do you currently manage the symptoms of your patients with IBS? Given the results of the TARGET trials, would you consider using rifaximin to treat your patients with IBS?