Lactulose Breath Testing Predicts Response to Rifaximin for Cardinal Irritable Bowel Syndrome With Diarrhea (IBS-D)

Abstract

Introduction: Rifaximin is a nonsystemic antibiotic indicated for IBS-D treatment in adults. We have previously shown that baseline lactulose breath testing (LBT) predicts higher likelihood (OR=4.3) of FDA-defined response to therapy (≥50% decrease from baseline in diarrhea and ≥30% decrease in abdominal pain). This analysis assessed use of LBT results before and after rifaximin to determine response to cardinal IBS-D symptoms. Methods: The TARGET 3 trial included adults with IBS-D (Rome III criteria). Eligible patients received open-label rifaximin 550 mg 3 times daily for 2 weeks, followed by a 4-week post-treatment period to assess response. Patients used at-home kits with 10 g of lactulose for LBT. LBT was conducted before (day 1) and after (day 14+5) therapy (sampled q 15 min; up to 240 min) in a subgroup of patients from 13 centers. Breath test results were categorized as positive or negative (H2 rise <20 ppm within 90 min of test and methane <10 ppm), based on the 2017 North American Consensus publication. After therapy, 4-week average daily scores and average daily score changes from baseline were compared based on LBT results. Results: Of 98 patients (mean age, 49.4 y; 67.3% female) with LBT data, 93 had interpretable results and no missing data at baseline; 62 (66.7%) had positive baseline LBT. Forty-five of 93 patients (48.4%) responded to rifaximin. There were no significant differences in demographics or IBS-D symptom profile according to LBT result, and none predicted therapy response. Compared with patients with a baseline negative LBT, patients with positive LBT had 70.6% and 70.7% more improvement in bloating and loose/watery bowel movements, respectively (P<0.001;Table 1). Patients with a positive LBT had significantly larger improvement in stool frequency, stool consistency, and abdominal pain compared with patients with negative breath test (Table 1). LBT results after rifaximin therapy did not predict response independently (P>0.05); however, patients whose LBT normalized after therapy reported the highest symptomatic improvement in bloating, urgency, diarrhea, stool consistency, and abdominal pain (Table 2). Conclusion: Currently, breath testing is the only biomarker available to independently predict higher response to rifaximin therapy for IBS-D symptoms, including bloating, abdominal pain, stool frequency, and stool consistency. The results are consistent with theories that there is an important role for the gut microbiota in IBS.468_A Figure 1 No Caption available.468_B Figure 2 No Caption available.