Celecoxib versus omeprazole and diclofenac in patients with osteoarthritis and rheumatoid arthritis (CONDOR): a randomised trial.
BACKGROUND
Cyclo-oxygenase (COX)-2-selective non-steroidal anti-inflammatory drugs (NSAIDs) and non-selective NSAIDs plus a proton-pump inhibitor (PPI) have similar upper gastrointestinal outcomes, but risk of clinical outcomes across the entire gastrointestinal tract might be lower with selective drugs than with non-selective drugs. We aimed to compare risk of gastrointestinal events associated with celecoxib versus diclofenac slow release plus omeprazole.


METHODS
We undertook a 6-month, double-blind, randomised trial in patients with osteoarthritis or rheumatoid arthritis at increased gastrointestinal risk at 196 centres in 32 countries or territories. Patients tested negative for Helicobacter pylori and were aged 60 years and older or 18 years and older with previous gastroduodenal ulceration. We used a computer-generated randomisation schedule to assign patients in a 1:1 ratio to receive celecoxib 200 mg twice a day or diclofenac slow release 75 mg twice a day plus omeprazole 20 mg once a day. Patients and investigators were masked to treatment allocation. The primary endpoint was a composite of clinically significant upper or lower gastrointestinal events adjudicated by an independent committee. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00141102.


RESULTS
4484 patients were randomly allocated to treatment (2238 celecoxib; 2246 diclofenac plus omeprazole) and were included in intention-to-treat analyses. 20 (0.9%) patients receiving celecoxib and 81 (3.8%) receiving diclofenac plus omeprazole met criteria for the primary endpoint (hazard ratio 4.3, 95% CI 2.6-7.0; p<0.0001). 114 (6%) patients taking celecoxib versus 167 (8%) taking diclofenac plus omeprazole withdrew early because of gastrointestinal adverse events (p=0.0006).


CONCLUSIONS
Risk of clinical outcomes throughout the gastrointestinal tract was lower in patients treated with a COX-2-selective NSAID than in those receiving a non-selective NSAID plus a PPI. These findings should encourage review of approaches to reduce risk of NSAID treatment.


BACKGROUND
Pfizer Inc.
Chan
Francis K L
FK
Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong SAR, China. fklchan@cuhk.edu.hk
Lanas
Angel
A
Scheiman
James
J
Berger
Manuela F
MF
Nguyen
Ha
H
Goldstein
Jay L
JL
D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000009:adverse effects*; D000897:Anti-Ulcer Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000208:ethnology; D000068579:Celecoxib; D052246:Cyclooxygenase 2 Inhibitors / Q000009:adverse effects; D004008:Diclofenac / Q000008:administration & dosage / Q000009:adverse effects*; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D041741:Lower Gastrointestinal Tract / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D009853:Omeprazole / Q000627:therapeutic use*; D010003:Osteoarthritis / Q000188:drug therapy* / Q000208:ethnology; D010437:Peptic Ulcer / Q000139:chemically induced / Q000517:prevention & control*; D011720:Pyrazoles / Q000008:administration & dosage / Q000009:adverse effects*; D012107:Research Design; D018570:Risk Assessment; D012307:Risk Factors; D013449:Sulfonamides / Q000008:administration & dosage / Q000009:adverse effects*; D016896:Treatment Outcome; D041742:Upper Gastrointestinal Tract / Q000187:drug effects
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000897:Anti-Ulcer Agents; D052246:Cyclooxygenase 2 Inhibitors; D011720:Pyrazoles; D013449:Sulfonamides; D004008:Diclofenac; D000068579:Celecoxib; D009853:Omeprazole