Breath Test May Predict Response to Rifaximin for IBS-D

By Marilynn Larkin

November 12, 2019

NEW YORK (Reuters Health) - Lactulose breath testing (LBT) may be useful in predicting response to rifaximin treatment for irritable bowel disease with diarrhea (IBS-D), a clinical study reveals.

"Breath testing is safe, non-invasive and based on exclusive biomarkers of the gut microbiome: hydrogen and methane," Dr. Ali Rezaie of Cedars-Sinai in Los Angeles, told Reuters Health by email.

Because it is based on gastrointestinal physiology, breath can be used to tailor treatment options, he noted. "This study further shows that breath testing can predict response to therapy."

Dr. Rezaie and colleagues analyzed data from a subgroup of 13 centers from the phase 3 TARGET 3 trial. Participants received open-label rifaximin 550 mg three times daily for two weeks, followed by a four-week posttreatment period to assess response.

LBT was conducted before (day 1) and after (day 14) therapy, with breath samples obtained every 15 minutes, up to 240 minutes. Response was assessed based on a decrease in abdominal pain from baseline of 30% or more; a decrease of 50% or more in the frequency of mushy/watery stool; symptom improvement; and the relationship of clinical outcomes to LBT results.

Preparation for breath testing included avoidance of highly fermentable products or a heavy meal for 24 hours before test and a 12-hour fasting period to minimize baseline residual fermentation products.

As reported online November 1 in the American Journal of Gastroenterology, 93 patients (mean age about 50; about 65% women and 90% white) were included in the study, including 62 (66.7%) with positive baseline LBT results.

Overall, 48.4% of patients responded to rifaximin, including 37 of 62 patients with a positive baseline LBT (59.7%) and 8 of 31 with a negative LBT (25.8%).

No significant differences in baseline demographics or IBS-D symptom profile were observed between responders and nonresponders.

"Patients with a positive breath test experienced significantly greater improvement in abdominal pain, bloating, diarrhea, stool consistency and urgency," Dr. Rezaie noted. "This suggests that rifaximin has a gut microbiome modulatory mechanism of action in IBS patients and breath test can predict response to therapy."

Patients whose LBT results normalized after rifaximin had the highest response rate, 76.5%.

With respect to safety, close to half of participants reported at least one adverse event (AE), during the open-label phase and up to 18 weeks of observation. The most common AEs were upper respiratory tract-related and were considered unrelated to the study drug.

One patient with a negative baseline LBT and two with a positive baseline LBT experienced headache that was considered drug-related.

The authors conclude, "A positive baseline LBT result predicted a higher likelihood of response to rifaximin in IBS-D, suggesting a gut microbiome modulatory mechanism of action for rifaximin."

"Medical decision-making is based upon cumulative assessment of all available objective and subjective data," Dr. Rezaie said. "There is no diagnostic test accuracy of 100%. Breath testing is no exception and should be interpreted along with clinical information."

Most insurance plans cover breath testing, he added.

Dr. Sang Hoon Kim, Chief, Division of Gastroenterology and Director, Biliary Endoscopy at NewYork-Presbyterian Queens in New York City, commented in an email to Reuters Health, "Given that IBS is a challenging clinical entity to manage, this study is encouraging and offers a potential breakthrough in the medical management of IBS."

"Rifaximin has been shown in multiple studies to improve bloating, stool consistency and global symptoms in patients with IBS-D," he said. "Certainly, a simple breath test to determine those most likely to benefit from rifaximin would be extremely useful for clinicians."

However, he noted, LBT is not available everywhere.

The study was funded by Salix Pharmaceuticals in collaboration with academic investigators and the US Food and Drug Administration. One author is Salix employee; Dr. Rezaie and a coauthor are consultants to the company, and Cedars-Sinai has a licensing agreement with the company.


Am J Gastroenterol 2019.