Antibiotic for Irritable Bowel Syndrome Shows Fewer Adverse Effects
News Author: Tinker Ready, CME Author: Laurie Barclay, MD, CME/CE Released: 04/05/2012. Developed and funded by MedScape.
Irritable bowel syndrome (IBS) is a widespread condition with symptoms including abdominal pain or cramps, excess gas or bloating, and visible abdominal distension, as well as diarrhea or constipation. Many agents currently available for pharmacotherapy may be associated with bothersome adverse effects, such as nausea, insomnia, palpitations, and decreased appetite.
Studies of medications available to treat IBS have mostly focused on efficacy, based on the number needed to treat, which does not reflect adverse effects. The objective of this systematic review and meta-analysis by Shah and colleagues was to compare these therapies in the number needed to harm as a result of adverse effects.
STUDY SYNOPSIS AND PERSPECTIVE
Patients who take the antibiotic rifaximin for IBS with diarrhea are far less likely to stop using the drug because of adverse effects than patients taking 2 other common IBS treatments, according to a study by Eric Shah, MBA, from the School of Medicine at the Texas Tech University Health Sciences Center in Lubbock. The study was published online March 26 and in the April print issue of the American Journal of Medicine.
A research team led by Mark Pimentel, MD, from the GI Motility Program at the Cedars-Sinai Medical Center in Los Angeles, California, reviewed 26 clinical trials of drugs for IBS with diarrhea and for IBS with constipation.
In forms of IBS with diarrhea, the review found that patients experienced fewer adverse effects from the antibiotic rifaximin than patients who used tricyclic antidepressants or stool-slowing alosetron. For every 2.3 and 2.6 patients who benefited from antidepressants or alosetron, respectively, 1 had to stop because of adverse events. With rifaximin, 846 patients benefited for each patient who could not tolerate the drug.
"Irritable bowel syndrome is a common disorder that is chronic and non-life threatening," the authors write. "Nevertheless, irritable bowel syndrome has a significant negative impact on quality of life. Few therapies are currently available for the treatment of irritable bowel syndrome and even fewer approved by the Food and Drug Administration, and as such this condition has a significant unmet need."
What About Other IBS Treatments?
Brennan Spiegel, MD, section chief for outcomes research at the Division of Digestive Diseases, University of California, Los Angeles, said in an email that the study offers "a different way of thinking about treatments in IBS, but has important limitations." Not all adverse effects are the same, so they cannot be compared in a meta-analysis, he told Medscape Medical News. Dr. Spiegel also noted that the study did not consider the problem of bacterial resistance to rifaximin and failed to consider several additional forms of IBS treatment, including "antispasmodics, fiber, peppermint oil, [selective serotonin reuptake inhibitors], neomycin, tegaserod, linaclotide, or so-called 'placebo without deception.' "
The authors report that they looked at treatments "deemed of merit by the American College of Gastroenterology task force" for IBS with diarrhea; namely, tricyclic antidepressants, alosetron, and rifaximin, Through a rating process by the American College of Gastroenterology Task Force (ACGTF), drugs for IBS were graded as 1 (strong) vs 2 (weak) and A (strong), B (moderate), or C (weak), based on the level of evidence. These 3 drugs are the only that received grades of 1B or higher from the ACGTF for IBS with diarrhea. The review included studies with descriptions of adverse events and the number of patients who discontinued treatment because of adverse effects such as dry mouth, flushing, constipation, and insomnia.
For IBS with constipation, the effort to compare treatments "is more challenging," the researchers write. Except for studies of lubiprostone, data on the treatment of IBS with constipation are "limited to small studies (with poor descriptions of side effects)." The researchers conclude that "lubiprostone and selective serotonin reuptake inhibitors appear safe."
The study was funded by the Beatrice and Samuel A. Seaver Foundation. Cedars-Sinai Medical Center has a licensing agreement with Salix Pharmaceuticals for use of rifaximin for IBS. One coauthor is a consultant for Prometheus, Forrest, Alkermes, and Salix Pharmaceuticals, which markets rifaximin. Dr. Pimentel holds patent rights to the discovery of rifaximin for IBS, is a consultant for Salix Pharmaceuticals, and serves on its scientific advisory board. The other authors have disclosed no relevant financial relationships. Dr. Spiegel reports receiving grants from Ironwood, Amgen, and Shire Pharmaceuticals. He also serves as a consultant to Ironwood, Prometheus, and Takeda.
Am J Med. 2012;125:381-393. Abstract