The Zelnorm epidemiologic study (ZEST): a cohort study evaluating incidence of abdominal and pelvic surgery related to tegaserod treatment

BMC Gastroenterology

Alexander M Walker⁷  Elena Rivero³  Braden Kuo⁵  Anthony Lembo⁶  David L Earnest²  Sherry Quinn¹  John D Seeger⁴ 

[1] OptumInsight, Waltham, MA, USA;Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA;Novartis Farmaceutica, Barcelona, Spain;1620 Tremont St, Suite 3300, Boston, MA, 02120, USA;Gastrointestinal Unit, Massachusetts General Hospital, Boston, MA, USA;Beth Israel Medical Center, Boston, MA, USA;World Health Information Science Consultants (WHISCON), Newton, MA, USA

关键词: Cohort study;    Tegaserod;    Abdominal surgery;   

Others  :  858279
DOI  :  10.1186/1471-230X-12-171

 received in 2012-05-09, accepted in 2012-11-22,  发布年份 2012

【 摘 要 】

Background

Pre-marketing clinical studies of tegaserod suggested an increased risk of abdominal surgery, particularly cholecystectomy. We sought to quantify the association between tegaserod use and the occurrence of abdominal or pelvic surgery, including cholecystectomy.

Methods

This cohort study was conducted within an insured population. Tegaserod initiators and similar persons who did not initiate tegaserod were followed for up to six months for the occurrence of abdominal or pelvic surgery. Surgical procedures were identified from health insurance claims validated by review of medical records. The incidence of confirmed outcomes was compared using both as-matched and as-treated analyses.

Results

Among 2,762 tegaserod initiators, there were 94 abdominal or pelvic surgeries (36 gallbladder): among 2,762 comparators there were 134 abdominal or pelvic surgeries (37 gallbladder) (hazard ratio HR] = 0.70, 95% confidence interval [C.I.] = 0.54-0.91 overall, HR = 0.98, 95% C.I. = 0.62-1.55 for gallbladder). Current tegaserod exposure compared to nonexposure was associated with a rate ratio [RR] of 0.68 (95% C.I. = 0.48-0.95) overall, while the RR was 0.99 (95% C.I. = 0.56-1.77) for gallbladder surgery.

Conclusions

In this study, tegaserod use was not found to increase the risk of abdominal or pelvic surgery nor the specific subset of gallbladder surgery.

【 授权许可】

   
2012 Seeger et al.; licensee BioMed Central Ltd.

【 图 表 】

【 参考文献 】

• [1]Jones BW, Moore DJ, Robinson SM, Song F: A systematic review of tegaserod for the treatment of irritable bowel syndrome. J Clin Pharm Ther 2002, 27:343-352.
• [2]Rivkin A: Tegaserod maleate in the treatment of irritable bowel syndrome: a clinical review. Clin Ther 2003, 25:1952-1974.
• [3]Wagstaff AJ, Frampton JE, Croom KF: Tegaserod: a review of its use in the management of irritable bowel syndrome with constipation in women. Drugs 2003, 63:1101-1120.
• [4]Schoenfeld P: Review article: the safety profile of tegaserod. Aliment Pharmacol Ther 2004, 20(Suppl. 7):25-30.
• [5]Zelnorm Package Insert: Novartis. 2004.
• [6]Schoenfeld P: Systematic review: incidence of abdominal/pelvic surgery amongst patients using tegaserod in randomized trials. Aliment Pharmacol Ther 2004, 19:263-269.
• [7]Lanza LL, Dreyer NA, Schultz NJ, Walker AM: Use of insurance claims in epidemiologic research: identification of peptic ulcers, GI bleeding, pancreatitis, hepatitis and renal disease. Pharmacoepidemiol Drug Saf 1995, 4:239-248.
• [8]Anderson JL, May HT, Bair TL, Muhlestein JB, Horne BD, Carlquist JF: Lack of association of tegaserod with adverse cardiovascular outcomes in a matched case–control study. J Cardiovasc Pharmacol Ther 2009, 14:170-175.
• [9]Loughlin J, Quinn S, Rivero E, Wong J, Huang J, Kralstein J, Earnest DL, Seeger JD: Tegaserod and the risk of cardiovascular ischemic events: an observational cohort study. J Cardiovasc Pharmacol Ther 2010, 15:151-157.
• [10]Quam L, Ellis LBM, Venus P, Clouse J, Taylor CG, Leatherman S: Using claims data for epidemiologic research: the concordance of claims-based criteria with the medical record and patient survey for identifying a hypertensive population. Med Care 1993, 31:498-507.
• [11]Rosenbaum PR, Rubin DB: The central role of the propensity score in observational studies for causal effects. Biometrika 1983, 70:41-55.
• [12]D'Agostino RB Jr: Propensity score methods for bias reduction in the comparison of a treatment to a non-randomized control group. Stat Med 1998, 17:2265-2281.
• [13]Seeger JD, Williams PL, Walker AM: An application of propensity score matching using claims data. Pharmacoepidemiol Drug Saf 2005, 14:465-476.
• [14]Cole JA, Yeaw JM, Cutone JA, Kuo B, Huang Z, Earnest DL, Walker AM: Abdominal and pelvic surgery among patients with irritable bowel syndrome. Dig Dis Sci 2005, 50:2268-2275.
• [15]Brinker A, Schech SD, Burgess M, Avigan M: An observational study of cholecystectomy in patients receiving tegaserod. Drug Saf 2007, 30:581-588.
• [16]Kennedy TM, Jones RH: Epidemiology of cholecystectomy and irritable bowel syndrome in a UK population. Br J Surg 2000, 87:1658-1663.
• [17]Hasler WL, Schoenfeld P: Systematic review: abdominal and pelvic surgery in patients with irritable bowel syndrome. Aliment Pharmacol Ther 2003, 17:997-1005.
• [18]Longstreth GF, Yao JF: Irritable bowel syndrome and surgery: a multivariable analysis. Gastroenterology 2004, 126:1665-1673.
• [19]Fisher RS, Thistle J, Lembo A, Novick J, O’Kane P, Chey WD, Beglinger C, Rueegg P, Shi V, Dogra A, Luo D, Earnest DL: Tegaserod does not alter fasting meal-induced biliary tract motility. Am J Gastroenterol 2004, 99:1572-1580.
• [20]Brinker A, Avigan M: Epidemiology of ischaemic colitis (letter). Aliment Pharmacol Ther 2004, 20:697-698.
• [21]Gallo-Torres H, Brinker A, Avigan M: Alosetron: ischemic colitis and serious complications of constipation. Am J Gastroenterol 2006, 101:1080-1083.