Treatment with rifaximin improves symptoms of irritable bowel disease (IBS) without constipation, according to a pair of linked controlled trials published in the NEJM today. 

IBS is common, but there are few treatments of proven efficacy. There is evidence that IBS patients may have alterations in gut microflora, and some studies suggest benefits from antibiotic treatment. Rifaximin is a broad-spectrum antibiotic with limited oral absorption and a low incidence of resistance: this paper reports two identical manufacturer-sponsored trials investigating its use in IBS. Participants were adults with IBS, excluding those with constipation-predominant IBS, who did not have adequate relief of symptoms at the time of screening and randomisation. They received rifaximin 550mg or matching placebo three times daily for two weeks and were followed up for a further 10 weeks. Primary end point was the proportion of patients who had adequate relief of global IBS symptoms; a key secondary end point was the proportion of patients who had adequate relief of IBS-related bloating. Endpoints were assessed weekly either directly or via telephone monitoring, and analyses were carried out on a modified intention-to-treat population including all those who took at least one dose of study drug.

Across the two studies, 1,260 patients were randomised: two took no study medication, leaving 1,258 for analysis. Most patients completed the full 12 weeks of the study – main reasons for discontinuation were withdrawal, adverse events, and loss to follow-up. Across both studies, more patients in the rifaximin group than in the placebo group achieved adequate global symptom relief, the primary outcome (40.7% vs. 31.7%, P<0.001), with similar results for the pre-specified key secondary outcome of IBS-related bloating (40.2% vs. 30.3%, P<0.001) and other secondary outcomes. Adverse events were similar in the two groups.

The authors conclude that in patients with IBS without constipation, two weeks treatment with rifaximin provides greater relief of symptoms than placebo. They note that only a proportion of patients responded, and discuss potential mechanisms for the effect: whatever this might be, it seems to involve a change in an underlying cause of IBS that is linked to the gut microflora.

An accompanying editorial discusses the trials. The author notes the ‘attractive’ findings of the study, but comments that the therapeutic gain is small with rates of response between 9% and 12%. Although there may be a subgroup of patients who seem to have significant benefit, it is not clear how this group might be identified. At present, the author concludes, more information is needed on the efficacy and safety of continued or intermittent use, and on the potential long-term consequences of treating a common condition with poorly absorbed broad-spectrum antibiotics. Until this is available, use of such treatments should be carefully restricted.