Celecoxib versus diclofenac plus omeprazole in high-risk arthritis patients: results of a randomized double-blind trial.
OBJECTIVE
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 > or =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.
Department of Medicine and Therapeutics, Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, Hong Kong SAR. fklchan@cuhk.edu.hk
Francis K L
FK
Chan
Lawrence C T
LC
Hung
Bing Y
BY
Suen
Vincent W S
VW
Wong
Aric J
AJ
Hui
Justin C Y
JC
Wu
Wai K
WK
Leung
Yuk T
YT
Lee
Ka F
KF
To
S C Sydney
SC
Chung
Joseph J Y
JJ
Sung
D000328:Adult; D000368:Aged; D001168:Arthritis / Q000188:drug therapy*; D000068579:Celecoxib; D004008:Diclofenac / Q000008:administration & dosage* / Q000009:adverse effects; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D004415:Dyspepsia / Q000139:chemically induced; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009853:Omeprazole / Q000008:administration & dosage* / Q000009:adverse effects; D010437:Peptic Ulcer / Q000139:chemically induced / Q000517:prevention & control; D011446:Prospective Studies; D011720:Pyrazoles; D012008:Recurrence; D013449:Sulfonamides / Q000009:adverse effects / Q000627:therapeutic use*
D011720:Pyrazoles; D013449:Sulfonamides; D004008:Diclofenac; D000068579:Celecoxib; D009853:Omeprazole