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Logo of jneuromotThis ArticleAims and ScopeInstructions to AuthorsE-SubmissionJournal of Neurogastroenterology and Motility
 
J Neurogastroenterol Motil. 2010 April; 16(2): 222.
Published online 2010 April 27. doi:  10.5056/jnm.2010.16.2.222
PMCID: PMC2879858

Comments on Tegaserod Trial on Irritable Bowel Syndrome

TO THE EDITOR: Irritable bowel syndrome (IBS) remains to be a challenge for the gastroenterologist, due to its high prevalence and impacts on poor quality of life (QOL) with unsatisfactory pharmacological treatments. Most of the current treatment modalities for IBS have been directed at symptom relief rather than pathophysiology of the condition, which is heterogenous and poorly understood.1 I read the recent articles by Kim et al.2 about the tegaserod effects on IBS with great interest. The efficacy and safety of tegaserod have been demonstrated by several large randomized controlled trials.3,4 However, tegaserod was taken off the market by a high chance of having a myocardial infarction, stroke or angina.5

Kim et al.2 showed the efficacy of 5-hydroxytryptamine 4 (5-HT4) agonist in Korean women with IBS with constipation. In this study, tegaserod showed the relief of overall IBS symptoms such as abdominal pain/discomfort, number of bowel movements and stool consistency. They used the composite score of symptom frequency and severity as an endpoint in treatment of IBS. The previously published pharmaceutical trial for IBS have used "adequate relief of abdominal pain and discomfort" or "satisfactory relief of IBS symptoms" as their primary outcome measure which led to approvals for alosetron and tegaserod by the Food and Drug Administration (FDA).6 An alternative method for defining a responder in an IBS treatment trial is to ask patients to report the frequency and severity of all IBS symptoms. Kim et al.2 showed the adequate symptom relief and good correlation between symptom composite score and IBS-QOL, which might show the usefulness of Korean IBS-QOL in IBS therapeutic trial. However, it is not clear whether reduction of sum-score of 22.5/96 (23.5%) was enough to define a responder. They conducted this trial as open arm without placebo control. The FDA have recommended investigators to provide rules, a priori, which allow classification of each participant as a responder or non-responder for the primary outcome.7 The secondary outcome is used to strengthen the results by showing concordance between individual symptoms and the primary outcome measure, addressing the mechanism of the intervention, and assessing the safety.6 Kim et al.2 also proposed QOL to be included as a therapeutic outcome.

Recently, there are many pharmaceutical trials including the next generation 5-HT agonists, such as Prucalopride, TD-5108, and ATI-7505 in IBS.8 I am hoping for the present study to strengthen the pharmaceutical research in IBS. The primary outcome variables provide the basis for judging the success or failure of an intervention, therefore, further studies on the outcome measurements in IBS drug trials, which can properly quantify drug responses, are warranted.

Footnotes

Conflicts of interest: None.

References

1. Chey WY, Jin HO, Lee MH, Sun SW, Lee KY. Colonic motility abnormality in patients with irritable bowel syndrome exhibiting abdominal pain and diarrhea. Am J Gastroenterol. 2001;96:1499–1506. [PubMed]
2. Kim YS, Choi SC, Park JM, et al. The effect of tegaserod on symptoms and quality of life in Korean women with irritable bowel syndrome with constipation. J Neurogastroenterol Motil. 2010;16:61–70. [PMC free article] [PubMed]
3. Müler-Lissner SA, Fumagalli I, Bardhan KD, et al. Tegaserod, a 5-HT(4) receptor partial agonist, relieves symptoms in irritable bowel syndrome patients with abdominal pain, bloating and constipation. Aliment Pharmacol Ther. 2001;15:1655–1666. [PubMed]
4. Novick J, Miner P, Krause R, et al. A randomized, double-blind, placebo-controlled trial of tegaserod in female patients suffering from irritable bowel syndrome with constipation. Aliment Pharmacol Ther. 2002;16:1877–1888. [PubMed]
5. Fayyaz M, Lackner JM. Serotonin receptor modulators in the treatment of irritable bowel syndrome. Ther Clin Risk Manag. 2008;4:41–48. [PMC free article] [PubMed]
6. Design of Treatment Trials Committee. Irvine EJ, Whitehead WE, et al. Design of treatment trials for functional gastrointestinal disorders. Gastroenterology. 2006;130:1538–1551. [PubMed]
7. Committee for Proprietary Medicinal Products (CPMP) CPMP). Committee for Proprietary Medicinal Products (CPMP): points to consider on adjustment for baseline covariates. Stat Med. 2004;23:701–709. [PubMed]
8. Shekhar C, Whorwell PJ. Emerging drugs for irritable bowel syndrome. Expert Opin Emerg Drugs. 2009;14:673–685. [PubMed]

Articles from Journal of Neurogastroenterology and Motility are provided here courtesy of The Korean Society of Neurogastroenterology and Motility