Tegaserod for the treatment of irritable bowel syndrome - PubMed (original) (raw)
Review
Tegaserod for the treatment of irritable bowel syndrome
B W Evans et al. Cochrane Database Syst Rev. 2004.
Update in
- Tegaserod for the treatment of irritable bowel syndrome and chronic constipation.
Evans BW, Clark WK, Moore DJ, Whorwell PJ. Evans BW, et al. Cochrane Database Syst Rev. 2007 Oct 17;(4):CD003960. doi: 10.1002/14651858.CD003960.pub3. Cochrane Database Syst Rev. 2007. PMID: 17943807 Review.
Abstract
Background: IBS is a complex disorder that encompasses a wide profile of symptoms. Current drug treatments for irritable bowel syndrome (IBS) are of limited value. Many target specific symptoms only. Tegaserod, a 5HT(4) partial agonist, represents a novel mechanism of action in the treatment of IBS.
Objectives: The objective of this review was to evaluate the efficacy and tolerability of tegaserod for the treatment of IBS in adults and adolescents aged 12 years and above.
Search strategy: MEDLINE 1966-November 2002 and EMBASE 1980-November 2002 were searched. The text and key words used included "tegaserod", "HTF 919", "irritable bowel", and "colonic diseases, functional". The Cochrane Central Register of Controlled Trials, the Inflammatory Bowel Disease Review Group Specialized Trials Register, and Science Citation Index were also searched. Proceedings from the British Society of Gastroenterology Annual Meeting, and Digestive Disease Week (1998-2002) were hand searched. The manufacturer of tegaserod was contacted. Relevant articles were retrieved, and their reference lists were also reviewed.
Selection criteria: Randomised or quasi-randomised controlled trials comparing tegaserod with placebo, no treatment or any other intervention (pharmacological or non-pharmacological) in subjects aged 12 years and above with a diagnosis of IBS, focusing on clinical endpoints were considered for review.
Data collection and analysis: Study inclusion and exclusion, data extraction and quality assessment was undertaken by two reviewers independently. Meta-analysis was performed where study populations, designs, outcomes, and statistical reporting allowed combination of data in a valid way, using the summary statistic relative risk with 95% CI. Eight short-term placebo-controlled studies fulfilled our inclusion criteria. These were predominantly conducted in women. Seven studies evaluated the efficacy of tegaserod on global gastrointestinal (GI) symptoms in patients with constipation-predominant IBS (C-IBS). One small study evaluated safety in patients with diarrhoea-predominant IBS.
Main results: The relative risk (RR) of being a responder in terms of global relief of GI symptoms was significantly higher with tegaserod 12 mg (RR 1.19, 95% CI 1.09, 1.29) and tegaserod 4 mg (RR 1.15, 95% CI 1.02, 1.31) compared with placebo, with a number needed to treat (NNT) of 14 and 20 respectively. When all tegaserod doses were combined and compared with placebo (n=4040), the RR of being a responder was 1.17 (95% CI 1.08, 1.27), with a NNT of 17. Although the pooled results indicate statistically significant benefit with tegaserod, the a priori minimal clinically important differences set in two of the four pooled studies were not reached. Tegaserod did not significantly improve the patients' individual symptoms of abdominal pain and discomfort although bowel habit showed a statistically significant improvement with tegaserod 4 mg and there was a non-significant trend in favour of tegaserod 12 mg. When GI symptoms were assessed separately, those indicative of GI motility such as number of bowel movements and days without bowel movements were generally improved with tegaserod although the proportion of patients experiencing diarrhoea was significantly higher in the tegaserod 12 mg group compared with placebo (RR 2.75, 95% CI 1.90, 3.97), with a number needed to harm (NNH) of 20. Effects of tegaserod on GI symptoms such as bloating, stool consistency, and straining were not consistent across the studies.
Reviewer's conclusions: Tegaserod appears to improve the overall symptomatology of IBS but there are currently few data on its effect on quality of life. In addition, more information is needed about its efficacy in men. It would also be of interest to know whether treatment with tegaserod leads either directly, or indirectly, to changes in visceral sensitivity or psychopathology, which are also considered important in the pathophysiology of this condition.
Comment in
- Review: tegaserod prompts global relief of symptoms in irritable bowel syndrome.
Irvine EJ. Irvine EJ. ACP J Club. 2004 Sep-Oct;141(2):44. ACP J Club. 2004. PMID: 15341464 No abstract available.
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