Rifaximin and Neomycin in the Treatment of Constipation IBS with Methane as a Biomarker on Breath Testing: Presidential Poster

Abstract

Purpose: Several investigators have determined that methane on breath testing is associated with constipation IBS (C-IBS). Whether reduction of methane production and/or altering methanogenic flora improves IBS-C is not known. Rifaximin has been proven effective in the treatment of non-C-IBS, but rifaximin alone has only a modest effect on methane eradication and improvement in constipation. In this double-blind placebo-controlled trial, we compared neomycin alone with rifaximin and neomycin in the treatment of methane-positive C-IBS. Methods: Consecutive C-IBS subjects (18-65 years of age) (Rome III criteria) were recruited after applying exclusion criteria. All subjects presented for a lactulose breath test after a 12-hour fast. Only subjects with methane level >3 ppm on at least one breath sample were enrolled. Subjects then completed a stool diary, questionnaire (100 point VAS scale for bloating, abdominal pain, constipation, diarrhea, and straining) and 2-week run-in phase. Subjects were then randomized to receive either neomycin 500 mg twice daily and placebo, or neomycin plus rifaximin 550 mg tid for 14 days in a double-blind fashion. Questionnaires were repeated weekly during treatment and for 4 weeks following completion of treatment. On the last week of follow-up, the stool diary was repeated. Results: Thirty two subjects were randomized/received drug (n=17 neomycin/placebo, n=15 neomycin/rifaximin). Baseline characteristics were not different between groups including baseline symptoms, gender, and age. By week two of treatment, the constipation VAS score was significantly less severe in neomycin/rifaximin (30.7±30.7) group vs neomycin/placebo (57.9±25.0) group (P=0.011). Similarly, bloating was significantly less severe in neomycin/rifaximin group compared to neomycin/placebo group, (45.1±33.3 vs 65.1±25.9; P=0.045). Constipation improvement had a durable response such that constipation remained significantly improved even 3 weeks following cessation of therapy (P<0.05). In addition, bloating and straining had durable improvement. In the neomycin/rifaximin group, the eradication of breath methane (≤3 ppm) was associated with a lower severity for constipation (26.6±19.0) compared to subjects with methane still present (67.2±32.1; P=0.041). Conclusion: Rifaximin combined with neomycin appears to be superior to neomycin alone in the treatment of C-IBS subjects with methane. The best determinant of improvement was the eradication of methane after treatment in the neomycin/rifaximin group. Disclosure - Dr. Mark Pimentel - Consultant: Salix Pharmaceuticals, Grant/Research Support: Salix Pharmaceuticals Dr. Christopher Chang - Grant/Research Support: Salix Pharmaceuticals Dr. John Dibaise - Grant/Research Support: Salix Pharmaceuticals Dr. Satish Rao - Grant/Research Support: Salix Pharmaceuticals, Advisory Committee/Board: Salix Pharmaceuticals, Other - Honorarium: Salix Pharmaceuticals. This research was supported by an industry grant from Salix Pharmaceuticals, inc.