Repeat treatment with rifaximin improves irritable bowel syndrome-related quality of life: a secondary analysis of a randomized, double-blind, placebo-controlled trial

Brooks D Cash, Mark Pimentel, Satish S C Rao, Leonard Weinstock, Lin Chang, Zeev Heimanson, Anthony Lembo, Brooks D Cash, Mark Pimentel, Satish S C Rao, Leonard Weinstock, Lin Chang, Zeev Heimanson, Anthony Lembo

Abstract

Background: Diarrhea-predominant irritable bowel syndrome (IBS-D) impairs patient quality of life (QOL). Rifaximin is an oral, nonsystemic antibiotic indicated for IBS-D. The objective of this secondary analysis was to evaluate rifaximin retreatment on IBS-related QOL in patients with IBS-D.

Methods: Patients received open-label rifaximin 550 mg three times daily for 2 weeks. Clinical responders [simultaneously meeting weekly response criteria for abdominal pain (⩾30% improvement from baseline in mean weekly pain score) and stool consistency (⩾50% decrease from baseline in number of days/week with Bristol Stool Scale (BSS) type 6 or 7 stools) during ⩾2 of first 4 weeks posttreatment] who relapsed during an up to 18-week treatment-free observation phase were randomly assigned to receive two 2-week courses of double-blind rifaximin or placebo, separated by 10 weeks. A validated 34-item IBS-QOL questionnaire examined patient responses in 8 domains.

Results: The 2579 patients receiving open-label rifaximin experienced a mean improvement from baseline in IBS-QOL overall score of 54.9%. Responders to open-label rifaximin (n = 1074 of 2438 evaluable; 44.1%) had significantly greater improvement from baseline in IBS-QOL overall and all eight subdomain scores, including dysphoria, food avoidance, interference with activity, body image, and sexual function versus nonresponders at 4 weeks posttreatment (n = 1364; p < 0.001 for all comparisons). A significantly greater percentage of responders to open-label rifaximin achieved the minimally clinically important difference (MCID; ⩾14-point improvement from baseline) in the overall IBS-QOL score versus nonresponders [n = 561 (52.2%) versus n = 287 (21.0%); p < 0.0001]. Among 636 patients with IBS-D relapse, the MCID in the overall IBS-QOL score was achieved by a significantly greater percentage of patients receiving double-blind rifaximin versus placebo (38.6% versus 29.6%, respectively; p = 0.009).

Conclusions: Open-label and blinded retreatment with a short course (2 weeks) of rifaximin improved IBS-QOL in patients with IBS-D [ClinicalTrials.gov identifier: NCT01543178].

Keywords: diarrhea; irritable bowel syndrome; quality of life.

Conflict of interest statement

Conflict of interest statement: Brooks Cash has served as a speaker, consultant, or as an advisory board member for Salix Pharmaceuticals and Valeant, Bridgewater, NJ; Takeda, Deerfield, IL; Ironwood, Boston, MA; AstraZeneca, Wilmington, DE; Allergan, Parsippany, NJ; and IM HealthSciences, LLC, Boca Raton, FL. Mark Pimentel has served as a consultant for and has received research funding from Salix Pharmaceuticals, Bridgewater, NJ. In addition, Cedars-Sinai Medical Center, Los Angeles, CA, has a licensing agreement with Salix Pharmaceuticals, Bridgewater, NJ. Satish Rao has received a research grant for rifaximin in IBS from Salix Pharmaceuticals, Bridgewater, NJ. Leonard Weinstock has served on the speakers’ bureau for Salix Pharmaceuticals, Bridgewater, NJ; Entera Health, Cary, NC; Allergan, Parsippany, NJ; and Romark Labs, Tampa, FL; and is a primary investigator on a rifaximin trial for IBS for Salix Pharmaceuticals, Bridgewater, NJ. Lin Chang has served on scientific advisory boards for Ironwood, Boston, MA; IM HealthSciences, LLC, Boca Raton, FL; BioAmerica, Miami, FL; Synthetics Biologics, Rockville, MD; and Synergy Pharmaceuticals Inc, New York, NY. She has served as a speaker for a Takeda (Deerfield, IL) CME conference and an Allergan (Parsippany, NJ) symposium. Zeev Heimanson is an employee of Salix Pharmaceuticals, Bridgewater, NJ. Anthony Lembo has served as a consultant and an advisory board member for Salix Pharmaceuticals and Valeant, Bridgewater, NJ; Ironwood, Boston, MA; Forest, New York, NY; Allergan, Parsippany, NJ; Prometheus, San Diego, CA; Alkermes, Waltham, MA; AstraZeneca, Wilmington, DE; and Ardelyx, Fremont, CA.

Figures

Figure 1.
Figure 1.
Study design. Reprinted with permission from Lembo and colleagues EOS, end of study; SC, stool sample collection; TID, three times daily.
Figure 2.
Figure 2.
Change from open-label baseline in IBS-QOL overall and subdomain scores for 1074 responders and 1364 nonresponders to open-label rifaximin at end of 4-week posttreatment follow-up. Positive numbers indicate improvement from baseline in IBS-QOL score. p < 0.001 for all comparisons (one-way ANOVA, with a factor of responder status). Number of patients with missing data: responder group (n = 61, overall and interference with activities; n = 57, sexual function; n = 60, dysphoria, body image, health worry, food avoidance, social reaction, and social relationship) and nonresponder group (n = 233, overall; n = 230, dysphoria, body image, food avoidance, health worry, and sexual function; n = 232, interference with activities, social reaction, and social relationship). ANOVA, analysis of variance; IBS-QOL, irritable bowel syndrome quality of life questionnaire.
Figure 3.
Figure 3.
Change from open-label baseline in IBS-QOL overall and subdomain scores at the 4-week posttreatment follow-up for responders who relapsed and were included in double-blind treatment phases (n = 636) compared with open-label responders who did not relapse during the open-label observation phase (n = 370). The p-value was based on a one-way ANOVA with a factor of evaluation-period status. Positive numbers indicate an improvement from baseline in IBS-QOL score. Number of patients with missing data: patients remaining relapse-free (n = 40, overall score, interference with activity, health worry, social reaction, and social relationships; n = 39, dysphoria, body image, and food avoidance; n = 37, sexual function) and patients with relapse (n = 18, overall score, dysphoria, interference with activity, body image, and food avoidance; n = 17, health worry, social reaction, sexual function, and social relationships). a, p = 0.02; b, NS; c, p = 0.002; d, p = 0.047; e, p = 0.01. ANOVA, analysis of variance; IBS-QOL, irritable bowel syndrome quality of life questionnaire; NS, not significant.
Figure 4.
Figure 4.
Change from open-label baseline in IBS-QOL overall and subdomain scores at last visit for patients randomly assigned to receive rifaximin (n = 328) or placebo (n = 308) in the double-blind treatment phases. The p-value was based on a one-way ANOVA, with a factor of treatment group, adjusted for analysis center, time to recurrence, and recurrence type. Positive numbers indicate an improvement from baseline in IBS-QOL score. Number of patients with missing data: rifaximin (n = 2, overall score, dysphoria, interference with activity, body image, and food avoidance; n = 1, health worry, social reaction, sexual function, and social relationships); placebo (n = 1, overall and all subdomains). a, p = 0.01; b, p = 0.02; c, p = 0.006; d, NS; e, p = 0.03; f, p < 0.001. ANOVA, analysis of variance; IBS-QOL, irritable bowel syndrome quality of life questionnaire; NS, not significant.
Figure 5.
Figure 5.
Change from double-blind baseline in IBS-QOL overall and subdomain scores 6 weeks after receiving the first double-blind repeat treatment for patients receiving two repeat treatments with rifaximin or placebo in the double-blind phase. Analysis was performed using per protocol population. Positive numbers indicate an improvement from baseline in IBS-QOL score. Number of patients with missing data: rifaximin (n = 3) and placebo (n = 2), overall and all subdomain scores. IBS-QOL, irritable bowel syndrome quality of life questionnaire.

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