Dr. Pimentel and his associates provided a supplementary appendix containing graphs showing that the percentage of patients with adequate relief of global IBS symptoms declined in both groups, in both studies, during the 10 weeks after treatment.
Two patients in the rifaximin group and five in the placebo group had serious adverse events. The incidence of infections was similar in the two groups. There were no cases of ischemic colitis and no deaths.
Regarding the mechanism of action, the authors noted several possible pathways. Besides altering the balance of the gut flora, the drug might also decrease gas associated with bacterial activity, reduce local inflammatory response to bacteria, or alter both the bacteria and host response.
“Whatever the final pathway, the durable effects suggest that rifaximin is affecting an underlying cause of IBS that is linked to an alteration in the intestinal microbiota,” they said.
In an accompanying editorial, Dr. Jan Tack of the University of Leuven, Belgium, noted the declining durability of rifaximin's effect and the relatively small difference between the active and placebo responses.
“The therapeutic gain, with the rates of response to treatment (i.e., adequate relief) ranging between 9 and 12% more with rifaximin than with placebo, is in the lower spectrum of what is considered to be clinically relevant,” he wrote. Dr. Tack also noted that since IBS is a chronic disorder, the follow-up period was relatively short (N. Eng. J. Med. 2011;364:81-2).
Despite the studies' positive findings, including the favorable safety profile, he wrote that “clinicians should proceed with caution.”
Although “rifaximin has the potential to provide a welcome addition to the limited armamentarium of agents that are available to treat IBS,” he also wrote that, “taking 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.”
Until researchers are able to identify a subgroup of patients that might respond well to the drug, “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,” he wrote.
Dr. Tack reported no financial relationship with Salix.