November 22, 1993

A Controlled Study Comparing the Effects of Nabumetone, Ibuprofen, and Ibuprofen Plus Misoprostol on the Upper Gastrointestinal Tract Mucosa

Author Affiliations

From the Arthritis Center of Excellence, Humana Hospital, Phoenix, Ariz (Dr Roth); Department of Medicine, Oregon Health Sciences University, Portland (Dr Tindall); Department of Medicine, Tulane University, New Orleans, La (Drs Jain and McMahon); Department of Medicine, University of Oklahoma College of Medicine, Tulsa (Dr April); Department of Medicine, University of Washington, Seattle (Dr Bockow); and Metroplex Clinical Research Center, Dallas, Tex (Drs Cohen and Fleischmann).

Arch Intern Med. 1993;153(22):2565-2571. doi:10.1001/archinte.1993.00410220073008

Background:  This study was developed to compare the incidence of endoscopically diagnosed ulcers in elderly patients taking nabumetone, ibuprofen, or concomitant ibuprofen/misoprostol. Further research is indicated to better establish the clinical relevance of these endoscopy findings.

Methods:  We conducted a prospective, multicenter, randomized, endoscopist-blinded, 12-week study involving 171 patients with osteoarthritis aged 60 years and older. Patients were randomized to receive nabumetone, 1000 mg (n=58); ibuprofen, 600 mg four times daily (n=53); or ibuprofen, 600 mg four times daily, administered concomitantly with misoprostol, 200 μg four times daily (n=60). Endoscopy was performed at baseline and at weeks 2, 6, and 12. Endoscopy results were scored on a scale of 1 to 9. Significant ulcers were defined as breaks in the mucosa greater than 5 mm with appreciable depth.

Results:  Of the 171 randomized patients, 148 completed the study. There was no significant difference in the incidence of significant ulcers between the nabumetone group and the ibuprofen/misoprostol group (one vs zero). There were significantly fewer significant ulcers in the nabumetone and ibuprofen/misoprostol groups than in the ibuprofen monotherapy group (one and zero vs eight; P<.01). There also was a significant difference in the time to ulcer development, with a greater risk of developing an ulcer sooner with ibuprofen treatment (P<.01) than either nabumetone or ibuprofen/misoprostol treatment. The severity of osteoarthritis, based on physicians' assessments, improved in 64% of patients in the nabumetone group, 55% of those in the ibuprofen group, and 63% of those in the ibuprofen/misoprostol group.

Conclusions:  Nabumetone is equivalent in ulcerogenicity to concomitant ibuprofen/misoprostol and is significantly less ulcerogenic than ibuprofen alone.(Arch Intern Med. 1993;153:2565-2571)