Alimentary TractA randomized trial comparing the effect of rofecoxib, a cyclooxygenase 2–specific inhibitor, with that of ibuprofen on the gastroduodenal mucosa of patients with osteoarthritis☆,☆☆,★
Section snippets
Patients
Patients with osteoarthritis ≥50 years old requiring NSAID treatment for at least 6 months were eligible. Patients were excluded if they had active duodenal, gastric, or esophageal ulcers; pyloric obstruction; or erosive esophagitis at baseline endoscopy. Patients with gastroduodenal erosions at baseline were eligible. Patients were excluded for past upper GI surgery; inflammatory bowel disease; serum creatinine level of >2.0 mg/dL; an estimated creatinine clearance of ≤30 mL/min; fecal occult
Results
Between December 1996 and August 1997, 1102 patients at 34 sites in the United States were screened and 742 were enrolled (Figure 1).
Discussion
We set out to test the hypothesis that the COX-2–specific inhibition with rofecoxib would have a lower incidence of gastroduodenal ulcers than NSAIDs in a long-term endoscopy study. An in vivo study of rofecoxib showed no significant effect on prostaglandin synthesis in human gastric mucosal biopsy specimens,15 and previous clinical studies suggested little or no GI tract injury with rofecoxib. In a 1-week double-blind endoscopic study, 250 mg rofecoxib once daily (20 times the dose shown to
Acknowledgements
The authors thank Jan Redfern and Kathleen Guckert for help with preparation of the manuscript; and Monica Hoover, Angeline Cagliola, Michelle Shelko, Sophia Haralson, and Francis D'Anzi for help in study implementation as well as database construction and review.
References (35)
Nonsteroidal anti-inflammatory drug gastropathy
Gastrointest Endosc Clin North Am
(1996)- et al.
Dif ferential inhibition of prostaglandin endoperoxide synthase (cyclooxygenase) isozymes by aspirin and other non-steroidal anti-inflammatory drugs
J Biol Chem
(1993) High-dose famotidine for prevention of NSAID ulcers?
Gastroenterology
(1997)- et al.
Comparison of salsalate and aspirin on mucosal injury and gastroduodenal mucosal prostaglandins
Gastroenterology
(1990) - et al.
A randomized double-blind comparison of placebo, etodolac, and naproxen on gastrointestinal injury and prostaglandin production
Gastrointest Endosc
(1995) - et al.
Comparison of the upper gastrointestinal safety of Ar throtec 75 and nabumetone in osteoarthritis patients at high risk for developing nonsteroidal anti-inflammatory drug–induced gastrointestinal ulcers
Clin Ther
(1999) - et al.
Has the impact of Helicobacter pylori therapy on ulcer recurrence in the United States been overstated: a meta-analysis of rigorously designed trials
Am J Gastroenterol
(1998) Helicobacter pylori and complicated ulcer diseases
Am J Med
(1996)- et al.
Localization of cyclooxygenase-2 and regulation of its expression in gastric ulcers in rats (abstr)
Gastroenterology
(1998) NSAID gastropathy: the second most deadly rheumatic disease? Epidemiology and risk appraisal
J Rheumatol
(1991)
FDA arthritis advisory committee meeting: postmarketing surveillance of nonsteroidal antiinflammatory drugs
Ar thritis Rheum
Misoprostol reduces serious gastrointestinal complications in patients with rheumatoid ar thritis receiving nonsteroidal anti-inflammatory drugs
Ann Intern Med
NSAID induced gastrointestinal complications: the ARAMIS perspective—1997
J Rheumatol
Nonsteroidal anti-inflammatory drugs and gastrointestinal disease
Adverse effects of nonsteroidal anti-inflammatory drugs on the gastrointestinal system
Ann Clin Lab Sci
Selectivity of nonsteroidal antiinflammatory drugs as inhibitors of constitutive and inducible cyclooxygenase
Proc Natl Acad Sci USA
A human whole blood assay for clinical evaluation of biochemical efficacy of cyclooxygenase inhibitors
Inflamm Res
Cited by (463)
Medical Treatment of Joint Disease
2018, Equine Surgery, Fifth EditionGastrointestinal safety and efficacy of long-term GCSB-5 use in patients with osteoarthritis: A 24-week, multicenter study
2016, Journal of EthnopharmacologyRheumatic Diseases and the Gastrointestinal Tract
2021, Aktuelle Rheumatologie
- ☆
Address requests for reprints to: Loren Laine, M.D., GI Liver Division, Department of Medicine (LAC 12-137), University of Southern California School of Medicine, 2025 Zonal Avenue, Los Angeles, California 90033. e-mail: [email protected]; fax: (323) 226-7573.
- ☆☆
Supported by a grant from Merck & Co., Inc., Whitehouse Station, New Jersey.
- ★
The following institutions and primary investigators participated in the Rofecoxib Osteoarthritis Endoscopy Group 044 Study. Hill Top Research, Ltd., Cincinnati, OH: R. Bath. Rush Center for Clinical Studies, Chicago, IL: J. Block. Metroplex Clinical Research Center, Dallas, TX: S. Cohen. William Beaumont Hospital, Birmingham, MI: M. Doyle. Garland and Associates, P.C., Lawrenceville, NJ: W. T. Garland. Veterans Administration Hospital, Houston, TX: M. Genta. Nashville Research Associates, Nashville, TN: D. Gremillion. University of California, San Diego, San Diego, CA: J. Isenberg. Rockford Gastroenterology Associates, Rockford, IL: J. Johanson. St. John's Health Center, Santa Monica, CA: W. Katkov. Medici Research Centers, LLC, Peoria, AZ: L. Kirby II. Northwestern Memorial Hospital/Northwestern Community Medical Group, Chicago, IL: J. Kopin. University of Southern California School of Medicine, Los Angeles, CA: L. Laine. Houston Institute for Clinical Research, Houston, TX: F. Lanza. New York Hospital–Cornell Medical Center, New York, NY: C. McDougall. The Penrose-St. Francis Medical Group, P.C., Colorado Springs, CO: E. Miller. Dayton Area Research Association, Kettering, OH: N. Patel. PSC Family Medicine, Louisville, KY: M. Peveler. Marshfield Medical Clinic, Marshfield, WI: C. Rall. Arizona Research and Education, Phoenix, AZ: S. Roth. Rush-Presbyterian–St. Luke's Medical Center, Chicago, IL: E. Ruderman. Cincinnati Gastroenterology, Cincinnati, OH: A. Safdi. California Research Foundation, San Diego, CA: B. Sahba. South Florida Center for Digestive Diseases, Miami, FL: H. Schwartz. Mid-Atlantic Medical Research Center, Hollywood, MD: U. Shah. Florida Medical Clinic, P.A., Zephyrhills, FL: D. Sikes. New Orleans Center for Clinical Research, New Orleans, LA: W. Smith. Clinical Interventions Research Institute, Mission Viejo, CA: D. Stanton. Northern California Medical Associates, Santa Rosa, CA: P. Stein. University of Louisville, Louisville, KY: S. Stern. Peninsula Gastroenterology Medical Group, Redwood City, CA: J. Torosis. Clinical Investigations Specialists, Inc., Little Rock, AK: L. Watkins. Mid-South Clinical Research Institute, Memphis, TN: L. Wruble. Physicians Quality Care Research, Baltimore, MD: T. Zizic.