PHILADELPHIA -- Treatment of diarrhea-predominant irritable bowel syndrome (IBS-D) with rifaximin was associated with significant symptomatic improvements, and treatment could be successfully repeated if patients relapsed, researchers reported here.
In an open-label study known as TARGET 3 that included 2,579 patients, a total of 42% of patients responded to 2 weeks of treatment according to the FDA's stringent criteria of at least a 30% reduction in pain and a 50% or greater decrease in the number of days with scores or 6 (loose) or 7 (watery) on the Bristol Stool Scale, according to Anthony Lembo, MD, of Harvard Medical School and Beth Israel Deaconess Medical Center in Boston, and colleagues.
Among those initial responders, 36% never relapsed over 18 to 22 weeks of follow-up, which was "very important," co-author Mark Pimentel, MD, told MedPage Today, at the American College of Gastroenterology meeting.
But when the other 64% who did relapse were randomized to a second blinded 2-week course of treatment or placebo, 33% on rifaximin again responded compared with 25% of those receiving placebo (P=0.02), even though these were more refractory patients, said Pimentel, who directs the gastrointestinal motility program at Cedars-Sinai Medical Center in Los Angeles.
After the second 2-week treatment course, those who again relapsed were re-randomized to the active treatment or placebo, and 37% of the rifaximin group responded compared with 29% of the placebo group (P=0.04), the researchers reported.
"Once again rifaximin beat placebo. This was like shooting arrows and hitting the bull's eye all three times," Pimentel observed.
"The main message of the study is that if you are retreated, you continue to have benefit for IBS, and there have been no new safety concerns," Lembo said in an interview.
It's now believed that a substantial number of patients with IBS have increased microbes in the small intestine, which suggested that antimicrobial treatment might have a role. Rifaximin was chosen because of its lack of absorption, suggesting that it wouldn't influence the colon microflora or encourage the development of antibiotic resistance.
The clinical trials TARGET 1 and 2 demonstrated the efficacy of this approach, according to Pimentel.
"So next we wanted to look at real-life use of this treatment," he said.
The regimen involved the administration of rifaximin, 550 mg three times daily for 2 weeks, followed by a 4-week treatment-free phase during which efficacy was assessed. Patients then were followed for up to 18 weeks for possible recurrences, and retreatment offered for patients whose symptoms returned.
In TARGET 3, while 42% were considered responders according to the strict criteria after the first course of treatment, 72% reported some degree of improvement, either in abdominal pain or stool scores, which was another important finding, Pimentel said.
Those who underwent retreatment after symptoms recurred were mostly women, whose mean age was 47.
Adverse events were similar in the active treatment and placebo groups, being reported by 43% of the rifaximin group and 46% of the placebo group. One patient in each group discontinued because of adverse events. There was one case of Clostridium difficileinfection in a patient in the rifaximin group who had been treated with ciprofloxacin.
The researchers also performed gene sequencing and cultures with antibiotic susceptibility testing, which showed that three courses of treatment led to no changes in bacterial sensitivity and no cross-resistance to other agents such as ciprofloxacin.
In summary, this treatment was effective, did not need to be taken chronically, and if patients needed retreatment, the drug was again effective with no development of resistance. Also, repeated course of treatment was not associated with an increase in the rate of opportunistic infections.
Rifaximin is currently approved for hepatic encephalopathy and travelers' diarrhea, and an FDA ruling on approval for IBS is expected in February 2015.
Lembo, Pimental and co-authors disclosed relevant relationships with various companies including Salix, Ironwood/Forest, Prometheus, AstraZeneca, GlaxoSmithKline, ZXPharma, and Takeda.
Fuente: http://www.medpagetoday.com/
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