Celecoxib versus diclofenac plus omeprazole in high-risk arthritis patients: Results of a randomized double-blind trial

doi:10.1053/j.gastro.2004.07.010

Gastroenterology

Volume 127, Issue 4, October 2004, Pages 1038-1043

https://doi.org/10.1053/j.gastro.2004.07.010 Get rights and content

Background & Aims: The gastric safety of cyclooxgenase-2 inhibitors and prophylactic antisecretory therapy in high-risk arthritis patients is unclear. We studied the ulcer incidence and factors predicting ulcer recurrence in a prospective, double-blinded trial. Methods: We studied patients who presented with nonsteroidal anti-inflammatory drug-associated ulcer bleeding. After ulcer healing, patients who were negative for Helicobacter pylori were randomly assigned to celecoxib 200 mg twice a day plus omeprazole placebo once daily or diclofenac 75 mg twice daily plus omeprazole 20 mg once daily for 6 months. Patients underwent endoscopy if they developed recurrent bleeding. Those without recurrent events underwent endoscopy at their last follow-up visit. Results: Two hundred eighty-seven patients were enrolled; 24 had recurrent gastrointestinal complications. Among 259 patients without events, 222 underwent endoscopy (116 received celecoxib and 106 received diclofenac plus omeprazole). The probability of recurrent ulcers in 6 months was 18.7% in the celecoxib group and 25.6% in the diclofenac plus omeprazole group (difference, −6.7%; 95% CI: −17.8% to 3.9%) (P = 0.21). Combining bleeding and endoscopic ulcers, 24.1% in the celecoxib group and 32.3% in the diclofenac plus omeprazole group had recurrent ulcers in 6 months (difference, −8.2%; 95% CI: −19.5% to 2.9%) (P = 0.15). Treatment-induced significant dyspepsia (hazard ratio, 5.3; 95% CI: 2.6–10.8), age ≥75 (hazard ratio, 2.0; 95% CI: 1.1–3.5), and comorbidity (hazard ratio, 2.1; 95% CI: 1.2–3.7) independently predicted ulcer recurrence. Conclusions: Among patients with previous ulcer bleeding, neither celecoxib nor diclofenac plus omeprazole adequately prevents ulcer recurrence. Treatment-induced significant dyspepsia is an indication for endoscopic evaluation.

Section snippets

Study population and setting

We screened consecutive patients with arthritis who presented with ulcer bleeding while receiving NSAIDs to the Endoscopy Center of Prince of Wales Hospital at The Chinese University of Hong Kong. The inclusion criteria were ulcer healing confirmed on follow-up endoscopy, a negative test for Helicobacter pylori or successful eradication of Helicobacter pylori based on histology, and anticipated regular use of NSAIDs for the duration of the trial. The exclusion criteria were concomitant use of

Results

A total of 287 patients were enrolled. Twenty-four patients developed recurrent GI bleeding; 7 in the celecoxib group and 9 in the diclofenac plus omeprazole group were adjudicated to have recurrent ulcer bleeding according to prespecified criteria.¹⁰ Among patients with recurrent ulcer bleeding, 3 used concomitant low-dose aspirin (1 in the celecoxib group and 2 in the diclofenac plus omeprazole group), and 1 who received diclofenac plus omeprazole had relapse of H. pylori infection. Eighteen

Discussion

We studied the overall incidence of ulcers to evaluate the gastric safety of long-term treatment with celecoxib or diclofenac plus omeprazole in very high-risk patients, i.e., those with a recent episode of ulcer bleeding. Among patients without recurrent gastrointestinal complications within the study period, the incidence of recurrent gastroduodenal ulcers was unexpectedly high: 19% of patients receiving celecoxib and 26% of patients receiving diclofenac plus omeprazole had recurrent ulcers

References (17)

L. Laine et al.
A randomized trial comparing the effect of rofecoxib, a cyclooxygenase 2-specific inhibitor, with that of ibuprofen on the gastroduodenal mucosa of patients with osteoarthritis
Gastroenterology
(1999)
L.A. Garcia Rodriguez et al.
Risk of upper gastrointestinal bleeding and perforation associated with individual non-steroidal anti-inflammatory drugs
Lancet
(1994)
L. Laine et al.
A randomized trial comparing the effect of rofecoxib, a cyclooxygenase 2-specific inhibitor, with that of ibuprofen on the gastroduodenal mucosa of patients with osteoarthritis
Gastroenterology
(1999)
J.F. Fries
NSAID gastropathythe second most deadly rheumatic disease? Epidemiology and risk appraisal
J Rheumatol
(1991)
G. Singh et al.
Epidemiology of NSAID-induced GI complications
J Rheumatol
(1999)
A. Rostom et al.
Prevention of NSAID-induced gastroduodenal ulcers
Cochrane Database Syst Rev
(2002)
L.S. Simon et al.
Anti-inflammatory and upper gastrointestinal effects of celecoxib in rheumatoid arthritisa randomized controlled trial
JAMA
(1999)
C. Bombardier et al.
Comparison of upper gastrointestinal toxicity of rofecoxib and naproxen in patients with rheumatoid arthritis. VIGOR Study Group
N Engl J Med
(2000)

There are more references available in the full text version of this article.

Cited by (150)

Pharmacoepidemiology of non-steroidal anti-inflammatory drugs
2019, Therapie
Non-steroidal anti-inflammatory drugs (NSAIDs) are reversible inhibitors of cyclo-oxygenase (COX), mainly used for the symptomatic relief of pain, whether traumatic, infectious, episodic or rheumatologic. Use for the long-term relief of inflammation is waning with the emergence of specific biotherapies. Their effects are related to potency, dosage, and pharmacokinetic or galenic considerations. Adverse reactions are mostly related to COX inhibition, and to the relative COX1 and COX2 inhibition. Over the years have resulted in the withdrawal of some NSAIDs. The most common adverse reactions are: gastrointestinal (COX1) which have declined over time with the emergence of more COX1 sparing drugs and gastroprotection; renal, with an impact on renal function and sodium extraction that is associated with hypertension, heart failure exacerbation, and stress-related renal failure; allergic skin reactions; increased transaminases and acute liver injury which may be idiosyncratic or immunoallergic; increased risk of acute coronary syndromes, initially associated with high-dose long-term use of COX2 specific inhibitors in controlled clinical trials, though more recently there have been indications from poorly controlled observational studies that they could occur with most NSAIDs. Event rates in patients with no overt coronary heart disease are vanishingly low, and the real magnitude of the issue in the treatment of common pain is still unknown. Considering their purely symptomatic effects, they should be used at the lowest possible dose for the shortest possible time, based on the symptomatic relief of pain or fever.
Safe prescription recommendations for non steroidal anti-inflammatory drugs: Consensus document ellaborated by nominated experts of three scientific associations (SER-SEC-AEG)
2014, Gastroenterologia y Hepatologia
Este artículo señala las recomendaciones claves para una adecuada prescripción de antiinflamatorios no esteroideos a pacientes que presentan indicación de tratamiento con esta medicación, en base a la evidencia científica actual y teniendo en consideración aspectos de seguridad gastrointestinal y cardiovascular. Las recomendaciones se han consensuado por expertos designados por 3 sociedades científicas (Sociedad Española de Reumatología, Asociación Española de Gastroenterología y Sociedad Española de Cardiología), siguiendo una metodología Delphi a 2 rondas. Las áreas que se han tenido en cuenta engloban: eficacia, riesgo cardiovascular, riesgo gastrointestinal, riesgo hepático, riesgo renal, enfermedad inflamatoria intestinal, anemia, dolor postoperatorio y estrategias de prevención. Se propone un algoritmo de manejo de pacientes que recoge los aspectos fundamentales de las recomendaciones.
This article outlines key recommendations for the appropriate prescription of non steroidal anti-inflammatory drugs to patients with different musculoskeletal problems. These recommendations are based on current scientific evidence, and takes into consideration gastrointestinal and cardiovascular safety issues. The recommendations have been agreed on by experts from three scientific societies (Spanish Society of Rheumatology [SER], Spanish Association of Gastroenterology [AEG] and Spanish Society of Cardiology [SEC]), following a two-round Delphi methodology. Areas that have been taken into account encompass: efficiency, cardiovascular risk, gastrointestinal risk, liver risk, renal risk, inflammatory bowel disease, anemia, post-operative pain, and prevention strategies. We propose a patient management algorithm that summarizes the main aspects of the recommendations
Safe prescription recommendations for non steroidal anti-inflammatory drugs: Consensus document ellaborated by nominated experts of three scientific associations (SER-SEC-AEG)
2014, Reumatologia Clinica
Este artículo señala las recomendaciones claves para una adecuada prescripción de antiinflamatorios no esteroideos a pacientes que presentan indicación de tratamiento con esta medicación, en base a la evidencia científica actual y teniendo en consideración aspectos de seguridad gastrointestinal y cardiovascular. Las recomendaciones se han consensuado por expertos designados por 3 sociedades científicas (Sociedad Española de Reumatología, Asociación Española de Gastroenterología y Sociedad Española de Cardiología), siguiendo una metodología Delphi a 2 rondas. Las áreas que se han tenido en cuenta engloban: eficacia, riesgo cardiovascular, riesgo gastrointestinal, riesgo hepático, riesgo renal, enfermedad inflamatoria intestinal, anemia, dolor postoperatorio y estrategias de prevención. Se propone un algoritmo de manejo de pacientes que recoge los aspectos fundamentales de las recomendaciones.
This article outlines key recommendations for the appropriate prescription of non steroidal anti-inflammatory drugs to patients with different musculoskeletal problems. These recommendations are based on current scientific evidence, and takes into consideration gastrointestinal and cardiovascular safety issues. The recommendations have been agreed on by experts from three scientific societies (Spanish Society of Rheumatology [SER], Spanish Association of Gastroenterology [AEG] and Spanish Society of Cardiology [SEC]), following a two-round Delphi methodology. Areas that have been taken into account encompass: efficiency, cardiovascular risk, gastrointestinal risk, liver risk, renal risk, inflammatory bowel disease, anemia, post-operative pain, and prevention strategies. We propose a patient management algorithm that summarizes the main aspects of the recommendations
Short-term celecoxib (celebrex) adjuvant therapy: a clinical trial study on COVID-19 patients
2022, Inflammopharmacology
Risk factors of poor prognosis and impairment of activities of daily living in patients with hemorrhagic gastroduodenal ulcers
2021, BMC Gastroenterology
Clinical guidelines for drug-related peptic ulcer, 2020 revised edition
2020, Gut and Liver

View all citing articles on Scopus

Supported by a research grant from the Health Services Research Committee of Hong Kong (HSRC S111009).

Dr. Francis Chan received a consulting fee from Pfizer in 2002.

View full text

Clinical-alimentary tractCelecoxib versus diclofenac plus omeprazole in high-risk arthritis patients: Results of a randomized double-blind trial

Section snippets

Study population and setting

Results

Discussion

Gastroenterology

Lancet

Gastroenterology

NSAID gastropathythe second most deadly rheumatic disease? Epidemiology and risk appraisal

J Rheumatol

Epidemiology of NSAID-induced GI complications

J Rheumatol

Prevention of NSAID-induced gastroduodenal ulcers

Cochrane Database Syst Rev

Anti-inflammatory and upper gastrointestinal effects of celecoxib in rheumatoid arthritisa randomized controlled trial

JAMA

Comparison of upper gastrointestinal toxicity of rofecoxib and naproxen in patients with rheumatoid arthritis. VIGOR Study Group

N Engl J Med

Clinical-alimentary tract
Celecoxib versus diclofenac plus omeprazole in high-risk arthritis patients: Results of a randomized double-blind trial