Abstract
Background and Aims: Tegaserod is a 5-HT4 receptor agonist approved for irritable bowel syndrome with constipation in women <65 years of age without a history of cardiovascular ischemic events. Safety data are presented from 2 external adjudications from the 2018 Gastrointestinal Drugs Advisory Committee meeting supporting tegaserod's reintroduction after its voluntary 2007 withdrawal. Withdrawal was based on an internal adjudication using pooled placebo-controlled tegaserod data to identify potential cardiovascular ischemic signals. Methods: An independent committee conducted an external adjudication to evaluate 24 possible cardiovascular ischemic events (tegaserod: n = 20; placebo: n = 4) identified internally. A second independent external adjudication further evaluated these events. Results: A total of 18,645 patients were included (tegaserod: n = 11,614; placebo: n = 7031). The first adjudication identified 14 (0.075%) events (tegaserod: n = 13 [0.11%]; placebo: n = 1 [0.014%]). All patients had ≥1 cardiovascular risk factor, and 11 had ≥2. The second adjudication identified 390 events, 24 (0.13%) were classified as probable new or worsening events (tegaserod: 18 [0.16%]; placebo: 6 [0.09%]). For tegaserod, 7 (0.06%) were coronary or cerebrovascular ischemic events compared with 1 (0.01%) for placebo (odds ratio, 4.24; 95% confidence interval, 0.52–34.74; P = .273). All tegaserod patients reporting cardiovascular events had ≥1 risk, including cardiovascular disease, hyperlipidemia, ≥55 years of age, hypertension, diabetes, obesity, and smoking. Women <65 years of age without a history of cardiovascular ischemic events and ≤1 cardiovascular risk factor receiving tegaserod experienced no major adverse cardiovascular event(s). Conclusions: Two independent, external adjudications suggest that tegaserod is safe for women <65 years of age with irritable bowel syndrome with constipation, no history of cardiovascular ischemic events, and ≤1 cardiovascular risk factor.
| Original language | English (US) |
|---|---|
| Pages (from-to) | e682-e695 |
| Journal | Clinical Gastroenterology and Hepatology |
| Volume | 20 |
| Issue number | 4 |
| DOIs | |
| State | Published - Apr 2022 |
Funding
Funding This work was funded by Alfasigma USA , Inc. Conflicts of interest The authors disclose the following: Brian E. Lacy has served on the scientific advisory board for Ironwood, Salix, Takeda, and Arena; as a consultant for Alfasigma, Allakos, Boston Pharmaceuticals, Urovant, and Viver; and received research funding from Salix and the Mayo Clinic. Darren M. Brenner has served as a speaker for Allergan, Ironwood, Salix, Takeda, and Alfasigma; served as an advisor/consultant for Allergan, Ironwood, Salix, Takeda, Bayer, Alfasigma, Arena, and Alnylam; and received research funding from the Irene D. Pritzker Foundation. William D. Chey has served as a board member for the American College of Gastroenterology, GI on Demand, International Foundation of Functional GI Disorders, and the Rome Foundation; has served as a consultant for AbbVie, Alfasigma, Allakos, Alnylam, Arena, Bayer, Biomerica, Cosmo, IM Health, Ironwood, QOL Medical, Phathom, Redhill, Ritter, Salix/Valeant, Takeda, Urovant, and Vibrant; has received grant/research support from Bioamerica, Commonwealth Diagnostics International, QOL Medical, Salix, and Vibrant; and owns stock/stock options in GI on Demand, Modify Health, and Ritter. Funding This work was funded by Alfasigma USA, Inc. Conflicts of interest The authors disclose the following: Brian E. Lacy has served on the scientific advisory board for Ironwood, Salix, Takeda, and Arena; as a consultant for Alfasigma, Allakos, Boston Pharmaceuticals, Urovant, and Viver; and received research funding from Salix and the Mayo Clinic. Darren M. Brenner has served as a speaker for Allergan, Ironwood, Salix, Takeda, and Alfasigma; served as an advisor/consultant for Allergan, Ironwood, Salix, Takeda, Bayer, Alfasigma, Arena, and Alnylam; and received research funding from the Irene D. Pritzker Foundation. William D. Chey has served as a board member for the American College of Gastroenterology, GI on Demand, International Foundation of Functional GI Disorders, and the Rome Foundation; has served as a consultant for AbbVie, Alfasigma, Allakos, Alnylam, Arena, Bayer, Biomerica, Cosmo, IM Health, Ironwood, QOL Medical, Phathom, Redhill, Ritter, Salix/Valeant, Takeda, Urovant, and Vibrant; has received grant/research support from Bioamerica, Commonwealth Diagnostics International, QOL Medical, Salix, and Vibrant; and owns stock/stock options in GI on Demand, Modify Health, and Ritter. The authors thank the committees that reviewed the supplemental new drug application for orally administered tegaserod submitted by Sloan Pharma for treating women with irritable bowel syndrome with constipation without a history of cardiovascular ischemic disease and with ≤1 cardiovascular disease risk factor. This study was sponsored by Alfasigma USA, Inc. Editorial and medical writing support was provided by Peloton Advantage, LLC, an OPEN Health company (Parsippany, NJ).
Keywords
- Cardiovascular Safety
- Constipation
- Irritable Bowel Syndrome
- Tegaserod
ASJC Scopus subject areas
- Gastroenterology
- Hepatology
