Clinical research study
Celecoxib compared with lansoprazole and naproxen to prevent gastrointestinal ulcer complications

https://doi.org/10.1016/j.amjmed.2005.04.031Get rights and content

Abstract

Purpose

Selective cyclooxygenase-2 (COX-2) inhibitors cause significantly fewer peptic ulcers than conventional nonselective nonsteroidal anti-inflammatory drugs (NSAIDs) in patients at low risk or high risk for peptic ulcers. On the other hand, proton pump inhibitor co-therapy has also been shown to be effective in preventing relapse of peptic ulcers in high-risk patients using nonselective NSAIDs. We compared the efficacy of a selective COX-2 inhibitor with that of proton pump inhibitor co-therapy in the reduction in the incidence of ulcer relapse in patients with a history of NSAID-related peptic ulcers.

Materials and methods

For this study, we recruited 224 patients who developed ulcer complications after NSAID use. We excluded patients who required concomitant aspirin treatment and who had renal impairment. After healing of ulcers and eradication of Helicobacter pylori, patients were randomly assigned to treatment with celecoxib 200 mg daily (n = 120) or naproxen 750 mg daily and lansoprazole 30 mg daily (n = 122) for 24 weeks. The primary endpoint was recurrent ulcer complications.

Results

During a median follow-up of 24 weeks, 4 (3.7%, 95% confidence interval [CI] 0.0%-7.3%) patients in the celecoxib group, compared with 7 patients (6.3%, 95% CI 1.6%-11.1%) in the lansoprazole group, developed recurrent ulcer complications (absolute difference −2.6%; 95% CI for the difference −9.1%-3.7%). Celecoxib was statistically non-inferior to lansoprazole co-therapy in the prevention of recurrent ulcer complications. Concomitant illness (hazard ratio 4.72, 95% CI 1.24-18.18) and age 65 years or more (hazard ratio 18.52, 95% CI 2.26-142.86) were independent risk factors for ulcer recurrences. Significantly more patients receiving celecoxib (15.0%, 95% CI 9.7-22.5) developed dyspepsia than patients receiving lansoprazole (5.7%, 95% CI 2.8-11.4. P = .02).

Conclusions

Celecoxib was as effective as lansoprazole co-therapy in the prevention of recurrences of ulcer complications in subjects with a history of NSAID-related complicated peptic ulcers. However, celecoxib, similar to lansoprazole co-therapy, was still associated with a significant proportion of ulcer complication recurrences. In addition, more patients receiving celecoxib developed dyspepsia than patients receiving lansoprazole and naproxen.

Section snippets

Study population

We screened patients, aged 18 years or older, who were admitted to the departments of medicine or surgery with upper GI bleeding while receiving NSAIDs. Endoscopy was performed within 24 hours after admission. Patients were recruited into the study if gastric and/or duodenal ulcer, defined as a break in the mucosa of at least 5 mm in diameter with unequivocal depth, was found on endoscopy and they had diseases (eg, osteoarthritis, rheumatoid arthritis) that were expected to require continuous

Characteristics of patients

A total of 376 patients with peptic ulcer bleeding while taking NSAIDs were screened for eligibility into the trial. Of these, 134 patients were excluded (Figure 1): 5 had erosions only on upper endoscopy, 5 failed endoscopic hemostasis, 9 declined to participate, 33 were taking concomitant aspirin or warfarin, 2 had previous gastric surgery, 2 had carcinoma of stomach on histology, 4 had active malignancy, 52 had abnormal laboratory findings (48 had elevated serum creatinine levels), 19 did

Discussion

Proton pump inhibitor co-therapy has been shown to reduce relapse of endoscopic peptic ulcers and peptic ulcer complications in patients receiving NSAIDs.3, 4 However, a small proportion of patients still developed relapse of ulcer bleeding after continued use of NSAIDs and proton pump inhibitor. The efficacy of proton pump inhibitor co-therapy may also be reduced in the absence of H. pylori infection.11

Recent studies suggest that selective COX-2 inhibitors have effective anti-inflammatory

Conclusion

Celecoxib was as effective as lansoprazole co-therapy in the reduction of ulcer complication recurrences in subjects with a history of NSAID-related peptic ulcers. However, celecoxib, similar to lansoprazole co-therapy, was still associated with a significant proportion of ulcer complication recurrences. In addition, more patients receiving celecoxib developed dyspepsia than did patients receiving lansoprazole and naproxen.6

Acknowledgment

We are indebted to Drs. Chi Kuen Chan, Chi Kin Hui, and Ka Fai Kwok for recruiting the patients and performing the endoscopy; to endoscopy nurses at the Queen Mary Hospital for their assistance; to Ms. April Wong for data management; and to Mr. Stanley Yeung for statistical calculations.

References (17)

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The study was supported by Peptic Ulcer Research Fund and Simon K.Y. Lee Gastroenterology Research Fund of the University of Hong Kong.

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