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Managing IBS with Diarrhea as a Microbiome Condition Lessens Misery

October 30, 2017
A new approach to managing diarrhea-based irritable bowel syndrome that treats the origin as a disease of the microbiome promises much a better outcome for patients,

With Mark Pimentel, MD, and Walter Park, MD

Irritable bowel syndrome affects approximately 10 to 15% of the United States adult population with an estimated 1/3 of these individuals expected to seek medical attention for their symptoms.1 As one of the most common disorders seen by primary care physicians, it is no surprise that IBS finds its way into the offices of pain specialists who also work to help manage gastrointestinal-related pain complaints.

Taking on a new approach to the management of irritable bowel syndrome, the type marked by diarrhea (IBS-D), may reduce patient misery, according to Mark Pimentel, MD, FRCP, executive director of the Medically Associated Science and Technology (MAST) program at Cedars-Sinai Medical Center in Los Angeles.

Thinking of IBS-D as a microbiome-based disease offers a key to improved management, Dr. Pimentel said in a plenary presentation, “Anti-vinculin antibodies multicenter validation of a diagnostic blood test for Irritable bowel syndrome,” at the 2017 World Congress of Gastroenterology at ACG2017.1

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New View of Diarrhea-Based IBS

“Irritable bowel syndrome is a microbiome disease that [often] starts from food poisoning,” Dr. Pimentel told Practical Pain Management. “I think most experts would agree that 60% of IBS-D originates from some form of gastroenteritis.'”

The concept may be new to many physicians, especially pain practitioners, Dr. Pimentel said. Some, he suspected, may still be treating IBS with anti-depressants.1

“In the gastrointestinal field, the stigma about IBS being psychologically driven has disappeared to a great extent. There is a benefit to treating IBS-D as a microbiome disease.”

Recent research by other investigators has also focused on the IBS-gut microbiome link, with some finding evidence that those with IBS have alterations in the composition of their gut microbiome.2

Further research has found rifaximin to be effective in treating IBS-D, said Dr. Pimentel. The drug targets the gut and can be taken orally three times a day for 14 days. Those who have a recurrence can be retreated with a 14-day course up to two times.

According to the FDA,3 which approved Xifaxan in 2015, its exact mechanism of action for IBS-D treatment remains unknown, but experts believe it is related to changes occurring due to the bacterial content of the gastrointestinal tract.

Favorable Results Reported from the TARGET Trials

Two trials—Target 1 and Target 2—established the safety and efficacy of rifaximin,4 said Dr. Pimentel. In these multicenter trials, 1,258 patients were randomly assigned to receive Xifaxan or placebo over 14 days, followed by a treatment-free follow-up period of 10 weeks.

The primary endpoint in the Target 1 and 2 studies was adequate relief of global IBS symptoms for at least two of the first four weeks post-treatment. Significantly more subjects in the drug group than the placebo group met that criteria (40.8% vs 31.2%;  P= 0.01) in the two studies combined.3

In addition, more patients in the rifaximin group reported abdominal pain relief (44.3% vs 36.3%, P = 0.03; 42.9% vs. 34.4%, P = 0.02) in Target 1 and Target 2, respectively.4 Adverse events were similar in both groups, with headache being the most commonly reported side effect, experienced by 38% of the medication-treated group and 42% in the group that received the placebo.4 No cases ofC.difficile-associated diarrhea were reported among trial participants.

Concerns about bacterial resistance have been addressed more recently,1 according to Dr. Pimentel.

“That was demonstrated not to happen,” he told Practical Pain Management. The aim of the most recent study, TARGET 3, was to access whether repeated treatment with rifaximin had a favorable effect on fecal bacterial antibiotic susceptibility.5 The research team, led by Dr. Pimentel, found that rifaximin exposure had no association with long-term cross-resistance of Bacterioidaceae, Enterobacteriaceae andEnterococcoceae organisms.

Another Effective Treatment Option

Dr. Pimentel focused on rifaximin in his presentation,1 but noted that another potential treatment for IBS-D, approved at the same time as rifaximin, is eluxadoline (Viberzi). This oral medication has been approved for oral administration (to be taken twice a day with a meal),6 according to FDA guidance. Eluxadoline appears to activate receptors in the nervous system that may reduce bowel contractions, and has been approved for adults with IBS-D.6

Walter Park, MD, a gastroenterologist at Stanford Health Care and assistant professor of medicine at Stanford University School of Medicine in Stanford, California, commented on Dr. Pimentel’s presentation for Practical Pain Management.

“The concept that you can use an antibiotic to treat IBS is a relatively new one,” he said, confirming that Dr. Pimentel has advanced the idea that the microbiome may play a key role in IBS with diarrhea. Rifaximin works differently than other drugs used for this condition, said Dr. Park.

“We don’t have an objective test for IBS-D, which is typically defined by the absence of other conditions,” Dr. Park said, ”This new drug and concept, therefore, may provide a useful, new tool.”.

Dr. Park reported no relevant disclosures. Dr. Pimentel serves on the advisory board for Salix Pharmaceuticals, which sponsored the plenary session on IBS-D.

Last updated on: March 5, 2019
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