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 was recently reintroduced for treating irritable bowel syndrome with constipation (IBS-C) in women < 65 years without a history of cardiovascular disease (CVD). Initial concerns over possible cardiovascular adverse events (AEs) in patients who did not fall within current regulatory guidelines led to its withdrawal in 2007. Therefore, we provide an overall safety analysis from tegaserod studies specific to the FDA-indicated population. Methods: Safety data in women < 65 years without a history of CVD were pooled from four, 12-week, randomized, placebo-controlled trials. Treatment-emergent AEs (TEAEs), severe TEAEs, TEAEs leading to discontinuation, and serious TEAEs are reported. Results: The pooled population included 1385 IBS-C patients who received tegaserod 6 mg BID and 1364 who received placebo (PBO). The mean age was 41.2 years for tegaserod and 40.8 years for PBO, and both populations were primarily white (~84%). For both tegaserod (14.2%) and PBO (12.1%), headache was the most frequent TEAE, followed by gastrointestinal (GI) TEAEs, such as abdominal pain (tegaserod: 12.3%; PBO: 10.9%), diarrhea (tegaserod: 8.6%; PBO: 3.9%), and nausea (tegaserod: 8.0%; PBO: 6.8%) (TABLE). The incidence of severe TEAEs was similar in the tegaserod and PBO groups (17.5% vs 15.8%). The most common severe TEAEs were abdominal pain (tegaserod: 5.1%; PBO: 4.0%) and diarrhea (tegaserod: 2.4%; PBO: 0.8%). Among subjects receiving tegaserod, 6.2% experienced a TEAE leading to discontinuation, which was slightly higher than for PBO (4.8%). GI symptoms were the most frequent TEAEs leading to discontinuation (abdominal pain [tegaserod: 1.4%; PBO: 1.0%]; diarrhea [tegaserod: 1.4%; PBO: 0.1%]). Serious TEAEs were experienced by 1.4% of tegaserod and 0.9% of PBO subjects. There were no suicide attempts on tegaserod 6 mg BID and one (0.1%) with PBO. Discussion: In the FDA-indicated population of women with IBS-C < 65 years without a history of CVD, tegaserod 6 mg BID was generally well tolerated. Headache was the most common TEAE for subjects receiving tegaserod 6 mg BID but occurred in only ~2% more subjects than PBO. Diarrhea led to drug discontinuation in a low number of patients taking tegaserod 6 mg BID. There were no significant differences in rates of serious AEs including those related to suicide events within this population.
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 – Consultant. QOL Medical – Grant/Research Support. 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.