P1131 (S0494). - Efficacy of Tegaserod 6 mg BID for Treating Irritable Bowel Syndrome With Constipation in Women <65 Years of Age Without Cardiovascular Risk Factors: A Pooled Analysis of 4 Clinical Trials
Assistant Professor of Medicine; Director, Center for Gastrointestinal Motility Dartmouth-Hitchcock Medical Center Lebanon, NH
Eric D. Shah, MD, MBA1, Brian E. Lacy, MD, PhD, FACG2, William D. Chey, MD, FACG3, Lin Chang, MD4, Darren M. Brenner, MD, FACG5; 1Dartmouth-Hitchcock Medical Center, Lebanon, NH; 2Mayo Clinic, Jacksonville, FL; 3University of Michigan Health System, Ann Arbor, MI; 4David Geffen School of Medicine at UCLA, Los Angeles, CA; 5Northwestern University Feinberg School of Medicine, Chicago, IL
Introduction: Tegaserod is a selective 5-HT4 receptor agonist approved for treating irritable bowel syndrome with constipation (IBS-C) at a dose of 6 mg BID in women < 65 years of age with no known history of cardiovascular (CV) disease. Methods: Pooled analyses included 4 studies evaluating the efficacy of tegaserod 6 mg BID on primary and secondary IBS-C–related endpoints in the indicated population. These studies were all 12-week randomized, placebo-controlled trials (RCTs) enrolling IBS-C patients with ≥3-month symptom histories. Based on the a priori population definition for these analyses, only data from women < 65 years of age with no known history of CV disease were included. The primary endpoint was a subjective global assessment (SGA) of relief of IBS-C symptoms, where responders were defined as rating themselves “considerably” or “completely” relieved ≥50% of the time or at least “somewhat relieved” 100% of the time over the last 4 weeks of the 12-week studies (50%/100% SGA). A key secondary endpoint was a ≥30% reduction in weekly abdominal pain intensity and ≥50% increase in stool frequency (≥1/week) for at least 6 of 12 weeks. Efficacy outcomes were reported as odds ratios (OR) with 95% confidence intervals (CI), and differences in treatment response rates were calculated using Cochran-Mantel-Haenszel estimates. Tolerability outcomes were recorded. Results: The study population included 2752 patients (tegaserod [n=1386]; placebo [n=1366]). The mean ages were 41.2 years for tegaserod 6 mg BID and 40.8 years for placebo, and the duration of IBS-C symptoms was approximately 15 years for each group. The pooled OR (95% CI) for achieving 50%/100% SGA response at 1 month was 1.95 (1.64, 2.31; P< .001) and 1.38 (1.18, 1.61; P< .001) during the last 4 visits. The 50%/100% SGA response rates for tegaserod 6 mg BID during the last 4 visits was 44.1% compared to 36.5% with placebo (difference [95% CI]: 7.7 [4.0, 11.3; P< .001]). Significant benefits were also observed in abdominal pain and stool frequency response for tegaserod 6 mg BID (36.0%) compared to placebo (24.3%; difference [95% CI]: 11.5 [8.1, 14.8]; P< .001). Adverse events were similar between groups. No significant CV events were observed. Discussion: Pooled analyses of 4 prospective RCTs involving 2752 patients with IBS-C demonstrated that tegaserod 6 mg BID effectively reduced symptoms of IBS-C compared to placebo. Adverse event rates were similar in the tegaserod and placebo groups.
Disclosures: Eric Shah indicated no relevant financial relationships. Brian Lacy: Alfasigma – Consultant. Arena – Advisory Committee/Board Member. Ironwood – Advisory Committee/Board Member. Salix/Bausch – Advisory Committee/Board Member. Urovant – Advisory Committee/Board Member. William Chey: Allergan – Consultant. Alnylam – Consultant. American College of Gastroenterology – Advisory Committee/Board Member. American Neurogastroenterology Motility Society – Advisory Committee/Board Member. Bayer – Consultant. Biomerica – Consultant. Biomerica – Grant/Research Support. Commonwealth Diagnostics International – Grant/Research Support. GI Health Foundation – Advisory Committee/Board Member. GI on Demand – Advisory Committee/Board Member. IM Health – Consultant. International Foundation of Functional GI Disorders – Advisory Committee/Board Member. Ironwood – Consultant. Phathom – Consultant. QOL Medical – Grant/Research Support. QOL Medical – Consultant. Ritter – Consultant. Ritter – Stockholder/Ownership Interest (excluding diversified mutual funds). Rome Foundation – Advisory Committee/Board Member. Salix – Grant/Research Support. Salix/Valeant – Consultant. Takeda – Consultant. Urovant – Consultant. Urovant – Grant/Research Support. Vibrant – Grant/Research Support. zespri – Grant/Research Support. Lin Chang: Alfasigma – Consultant. Darren Brenner: Alfasigma – Consultant. Irene D. Pritzker Foundation – Grant/Research Support.