Evaluation of Rifaximin Efficacy in Non C-IBS Patients by Baseline Disease Severity: Subanalysis of the TARGET 1 and TARGET 2 Studies

Abstract

Purpose: Short term therapy with rifaximin for 2 weeks (Weeks 1-2) has demonstrated significant improvement in patients suffering from non-constipating IBS (non C-IBS) during primary follow up period (Weeks 3-6), in two double-blind placebo controlled trials. The benefit of rifaximin in non C-IBS patients based upon their baseline severity has not been reported previously. Methods: Patients with non C-IBS were randomized to rifaximin 550 mg TID or placebo for 2 weeks (TARGET 1, n=623; TARGET 2, n=637) and followed for 10 weeks post treatment. TARGET 1 & 2 were of identical design and independently conducted, with a primary endpoint defined as the percentage of responders having weekly adequate relief of IBS symptoms for ≥2 of the 4 weeks during the 4 weeks after completion of the study medication (Weeks 3-6). Adequate relief of bloating, a key secondary endpoint, was similarly evaluated. Other secondary endpoints utilized daily assessments of IBS symptoms, bloating, stool consistency and abdominal pain and discomfort. Analyses of efficacy endpoints by severity were performed on the pooled data. Severity was categorized as mild, moderate or severe (IBS-QOL ≥57, <57 and >40, and ≤40, respectively) based on a recently published international survey of IBS patients. The respective n numbers for placebo and rifaximin in the overall and within each severity category were as follows: overall, 634 and 624; mild, 258 and 254; moderate, 190 and 195; severe, 184 and 172. A logistic regression was performed to formally test for treatment by severity interaction for all endpoints to test for consistency across severity categories. Results: There was no treatment interaction between rifaximin and disease severity indicating consistent treatment effect across all severity categories. The combined analysis demonstrated a numerical and/or statistically significant treatment effect in favor of rifaximin in patients with mild, moderate and severe non C-IBS (Figure). In some analyses, statistical significant differences were limited by inadequate sample size.FigureConclusion: Patients with mild, moderate and severe non C-IBS appear to derive benefit from treatment with rifaximin 550 mg TID for 14 days in the month following cessation of therapy. Research was funded by Salix Pharmaceuticals Inc, Morrisville, NC. Disclosure: Dr. Pimentel reports receiving grant support (to his institution) and consulting fees and honoraria from Salix Pharmaceuticals and reports that Cedars-Sinai Medical Center holds patents licensed by Salix Pharmaceuticals; Dr. Lembo reports receiving consulting fees from Salix Pharmaceuticals, Ironwood Pharmaceuticals, Prometheus, Ardelyx, Theravance, GlaxoSmithKline, and AstraZeneca, receiving payment for participation in several advisory-board meetings relating to the development of rifaximin for the treatment of IBS; Dr. Chey reports payment as a consultant from Albireo, Astra-Zeneca, Forest, Ironwood, Johnson & Johnson, Proctor & Gamble, Prometheus, Salix, Takeda, Xenoport and payment for the development of educational presentations from Procter & Gamble, Prometheus, and Salix Pharmaceuticals; Dr. Yu, Dr. Merchant, and Dr. Bortey report being employees of and holding stock in Salix Pharmaceuticals; and Dr. Forbes reports being an officer and employee of Salix Pharmaceuticals and holding stock in the company. This study was sponsored by Salix Pharmaceuticals Inc, Morrisville, NC.