TY - JOUR
T1 - Assessment of upper gastrointestinal safety of etoricoxib and diclofenac in patients with osteoarthritis and rheumatoid arthritis in the Multinational Etoricoxib and Diclofenac Arthritis Long-term (MEDAL) programme
T2 - a randomised comparison
AU - Laine, Loren
AU - Curtis, Sean P.
AU - Cryer, Byron
AU - Kaur, Amarjot
AU - Cannon, Christopher P.
N1 - Funding Information:
The authors thank the following individuals from Merck Research Laboratories: Yanqiong Zhang for statistical support, Judith K Evans for assistance in formatting of the manuscript, and Laurine G Connors and Gary Swergold for their substantial contributions to the conduct and monitoring of the MEDAL programme. This work was supported by Merck & Co (Whitehouse Station, NJ, USA).
Funding Information:
L Laine has received research support from Merck, Pfizer, Novartis, TAP, and Bayer, and has served as a consultant for Merck, Novartis, Bayer, AstraZeneca, Eisai, Altana, J&J, and Santarus. S P Curtis and A Kaur are employees of Merck and own stock and/or hold stock options in the company. B Cryer has served as a consultant for Merck, Pfizer, AstraZeneca, and TAP. C P Cannon has received research grant support from Accumetrics, AstraZeneca, Merck, Merck/Schering Plough Partnership, and Schering Plough through the Department of Medicine of Brigham and Women's Hospital; has served on scientific advisory boards for Alnylam, AstraZeneca, Biosite, Bristol-Myers Squibb, Eisai, GlaxoSmithKline, Merck, Merck Schering Plough Partnership, Pfizer, Sanofi-Aventis, Schering Plough, and Tethys; has received lecture fees from Accumetrics, AstraZeneca, Bristol-Myers Squibb, Merck, Merck/Schering Plough Partnership, Pfizer, Sanofi-Aventis, and Schering Plough; has received honoraria for the preparation of educational materials from BGB New York, DIME, and NCME; and has received additional funding for studies and subsidies conducted by the TIMI study group from Merck and Co, Bristol-Myers Squibb Pharmaceutical Research Institute, Sanofi-Aventis, Millennium Pharmaceuticals, Nuvelo, AstraZeneca Pharmaceuticals, CV Therapeutics, Inotek Pharmaceuticals Corporation, Bayer Healthcare LLC, Ortho-Clinical Diagnostics, Sanofi-Synthelabo Recherche, GlaxoSmithKline, Amgen, Beckman Coulter, Biosite Coulter, Biosite Incorporated, Roche Diagnostics Corporation, Roche Diagnostics GmbH, Pfizer, Accumetrics, the National Institutes of Health, and Novartis Pharmaceuticals.
PY - 2007/2/10
Y1 - 2007/2/10
N2 - Background: Upper gastrointestinal safety of cyclo-oxygenase (COX)-2 selective inhibitors versus traditional non-steroidal anti-inflammatory drugs (NSAIDs) has not been assessed in trials that simulate standard clinical practice. Our aim was to assess the effects of these drugs on gastrointestinal outcomes in a population that includes patients taking gastrointestinal protective therapy. Methods: A prespecified pooled intent-to-treat analysis of three double-blind randomised comparisons of etoricoxib (60 or 90 mg daily) and diclofenac (150 mg daily) in 34 701 patients with osteoarthritis or rheumatoid arthritis was done for upper gastrointestinal clinical events (bleeding, perforation, obstruction, or ulcer) and the subset of complicated events (perforation, obstruction, witnessed ulcer bleeding, or significant bleeding). We also assessed such outcomes in patients who were taking concomitant proton pump inhibitors (PPIs) or low-dose aspirin. These trials are registered with ClinicalTrials.gov, with the numbers NCT00092703, NCT00092742, and NCT00250445. Findings: Overall upper gastrointestinal clinical events were significantly less common with etoricoxib than with diclofenac (hazard ratio [HR] 0·69, 95% CI 0·57-0·83; p=0·0001). There were significantly fewer uncomplicated gastrointestinal events with etoricoxib than there were with diclofenac (0·57, 0·45-0·74; p<0·0001); there was no difference in complicated events (0·91, 0·67-1·24; p=0·561). PPIs were used concomitantly for at least 75% of the study period by 13 862 (40%) and low-dose aspirin by 11 418 (33%) patients; treatment effects did not differ significantly in these individuals. Interpretation: There were significantly fewer upper gastrointestinal clinical events with the COX-2 selective inhibitor etoricoxib than with the traditional NSAID diclofenac due to a decrease in uncomplicated events, but not in the more serious complicated events. The reduction in uncomplicated events with etoricoxib is maintained in patients treated with PPIs and is also observed with regular low-dose aspirin use.
AB - Background: Upper gastrointestinal safety of cyclo-oxygenase (COX)-2 selective inhibitors versus traditional non-steroidal anti-inflammatory drugs (NSAIDs) has not been assessed in trials that simulate standard clinical practice. Our aim was to assess the effects of these drugs on gastrointestinal outcomes in a population that includes patients taking gastrointestinal protective therapy. Methods: A prespecified pooled intent-to-treat analysis of three double-blind randomised comparisons of etoricoxib (60 or 90 mg daily) and diclofenac (150 mg daily) in 34 701 patients with osteoarthritis or rheumatoid arthritis was done for upper gastrointestinal clinical events (bleeding, perforation, obstruction, or ulcer) and the subset of complicated events (perforation, obstruction, witnessed ulcer bleeding, or significant bleeding). We also assessed such outcomes in patients who were taking concomitant proton pump inhibitors (PPIs) or low-dose aspirin. These trials are registered with ClinicalTrials.gov, with the numbers NCT00092703, NCT00092742, and NCT00250445. Findings: Overall upper gastrointestinal clinical events were significantly less common with etoricoxib than with diclofenac (hazard ratio [HR] 0·69, 95% CI 0·57-0·83; p=0·0001). There were significantly fewer uncomplicated gastrointestinal events with etoricoxib than there were with diclofenac (0·57, 0·45-0·74; p<0·0001); there was no difference in complicated events (0·91, 0·67-1·24; p=0·561). PPIs were used concomitantly for at least 75% of the study period by 13 862 (40%) and low-dose aspirin by 11 418 (33%) patients; treatment effects did not differ significantly in these individuals. Interpretation: There were significantly fewer upper gastrointestinal clinical events with the COX-2 selective inhibitor etoricoxib than with the traditional NSAID diclofenac due to a decrease in uncomplicated events, but not in the more serious complicated events. The reduction in uncomplicated events with etoricoxib is maintained in patients treated with PPIs and is also observed with regular low-dose aspirin use.
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U2 - 10.1016/S0140-6736(07)60234-7
DO - 10.1016/S0140-6736(07)60234-7
M3 - Article
C2 - 17292766
AN - SCOPUS:33846822336
VL - 369
SP - 465
EP - 473
JO - The Lancet
JF - The Lancet
SN - 0140-6736
IS - 9560
ER -