TY - JOUR
T1 - Comparison of lumiracoxib with naproxen and ibuprofen in the Therapeutic Arthritis Research and Gastrointestinal Event Trial (TARGET), reduction in ulcer complications
T2 - Randomised controlled trial
AU - Schnitzer, Thomas J
AU - Burmester, Gerd R.
AU - Mysler, Eduardo
AU - Hochberg, Marc C.
AU - Doherty, Michael
AU - Ehrsam, Elena
AU - Gitton, Xavier
AU - Krammer, Gerhard
AU - Mellein, Bernhard
AU - Matchaba, Patrice
AU - Gimona, Alberto
AU - Hawkey, Christopher J.
N1 - Funding Information:
TJS has acted as a consultant for AAI Pharma, GlaxoSmithKline, McNeil Consumer Healthcare, Merck, Novartis, Pfizer, and Winston; has received clinical research support from AAI Pharma, Merck, Novartis, Pfizer, and Winston; and is a member of the speakers' bureau for Merck and Ortho-McNeil. CJH has received research funding or honoraria from AstraZeneca, GlaxoSmithKline, Merck, Nitromed, Novartis, Pfizer, Takeda, and Wyeth. GRB has done clinical trials, acted as a scientific consultant, and is member of the speakers' bureau for Novartis, Pfizer, Merck Sharp and Dohme, and Merckle. EM has received consultancy fees from Novartis. MCH has acted as a consultant for Amgen, Arakis, AstraZeneca, Aventis Pharmaceutical, Bristol Myers Squibb, Genzyme, GlaxoSmithKline, Laboratories NEGMA, Merck, Novartis, Proctor and Gamble Pharmaceutical, Purdue Pharma, Roche, Scios, and Takeda Pharmaceuticals North America; and has received clinical research support from Merck and GlaxoSmithKline. MD has received genetic research funding from GlaxoSmithKline and AstraZeneca and has received honoraria for attending advisory boards related to osteoarthritis products from Novartis, Aventis, Genzyme, Bristol Myers Squibb, Johnson and Johnson, and Merck. EE, XG, GK, BM, and PM are employees of Novartis, manufacturer of lumiracoxib. AG was an employee of Novartis until March, 2004.
Funding Information:
This work was supported by Novartis Pharma AG, Basel, Switzerland. Marie-Christine Domec acted as clinical trial leader until November, 2003.
PY - 2004/8/21
Y1 - 2004/8/21
N2 - Background Cyclo-oxygenase 2 (COX2)-selective inhibitors should reduce ulcer complications compared with non-selective non-steroidal anti-inflammatory drugs, but evidence is limited, and the possibility that these inhibitors increase cardiovascular events has been raised. The Therapeutic Arthritis Research and Gastrointestinal Event Trial (TARGET) aimed to assess gastrointestinal and cardiovascular safety of the COX2 inhibitor lumiracoxib compared with two non-steroidal anti-inflammatory drugs, naproxen and ibuprofen. Methods 18 325 patients age 50 years or older with osteoarthritis were randomised to lumiracoxib 400 mg once daily (n=9156), naproxen 500 mg twice daily (4754), or ibuprofen 800 mg three times daily (4415) for 52 weeks, in two substudies of identical design (lumiracoxib vs ibuprofen or naproxen). Randomisation was stratified for low-dose aspirin use and age. The primary endpoint was the difference in time-to-event distribution of upper gastrointestinal ulcer complications (bleeding, perforation, or obstruction); analysis was by modified intention to treat. The principle measure of adverse cardiovascular events was the Antiplatelet Trialists' Collaboration endpoint (myocardial infarction, stroke, or cardiovascular death); this analysis was intention to treat. Findings 81 (0·44%) patients did not start treatment and 7120 (39%) did not complete the study. In patients not taking aspirin, the cumulative 1-year incidence of ulcer complications was 1·09% (95% CI 0·82-1·36) with non-steroidal anti-inflammatory drugs (64 events) versus 0·25% (95% CI 0·12-0·39) with lumiracoxib (14 events; hazard ratio 0·21 [95% CI 0·12-0·37], p<0·0001). Reductions in ulcer complications were also significant in the overall population (0·34 [0·22-0·52], p<0·0001) but not in those taking aspirin (0·79 [0·40-1·55], p=0·4876). In the overall population, 0·55% (50/9127) of those on non-steroidal anti-inflammatory drugs and 0·65% (59/9117) of those on lumiracoxib reached the cardiovascular endpoint (1·14 [0·78-1·66], p=0·5074). Interpretation Lumiracoxib showed a three to four-fold reduction in ulcer complications compared with non-steroidal anti-inflammatory drugs without an increase in the rate of serious cardiovascular events, suggesting that lumiracoxib is an appropriate treatment for patients with osteoarthritis.
AB - Background Cyclo-oxygenase 2 (COX2)-selective inhibitors should reduce ulcer complications compared with non-selective non-steroidal anti-inflammatory drugs, but evidence is limited, and the possibility that these inhibitors increase cardiovascular events has been raised. The Therapeutic Arthritis Research and Gastrointestinal Event Trial (TARGET) aimed to assess gastrointestinal and cardiovascular safety of the COX2 inhibitor lumiracoxib compared with two non-steroidal anti-inflammatory drugs, naproxen and ibuprofen. Methods 18 325 patients age 50 years or older with osteoarthritis were randomised to lumiracoxib 400 mg once daily (n=9156), naproxen 500 mg twice daily (4754), or ibuprofen 800 mg three times daily (4415) for 52 weeks, in two substudies of identical design (lumiracoxib vs ibuprofen or naproxen). Randomisation was stratified for low-dose aspirin use and age. The primary endpoint was the difference in time-to-event distribution of upper gastrointestinal ulcer complications (bleeding, perforation, or obstruction); analysis was by modified intention to treat. The principle measure of adverse cardiovascular events was the Antiplatelet Trialists' Collaboration endpoint (myocardial infarction, stroke, or cardiovascular death); this analysis was intention to treat. Findings 81 (0·44%) patients did not start treatment and 7120 (39%) did not complete the study. In patients not taking aspirin, the cumulative 1-year incidence of ulcer complications was 1·09% (95% CI 0·82-1·36) with non-steroidal anti-inflammatory drugs (64 events) versus 0·25% (95% CI 0·12-0·39) with lumiracoxib (14 events; hazard ratio 0·21 [95% CI 0·12-0·37], p<0·0001). Reductions in ulcer complications were also significant in the overall population (0·34 [0·22-0·52], p<0·0001) but not in those taking aspirin (0·79 [0·40-1·55], p=0·4876). In the overall population, 0·55% (50/9127) of those on non-steroidal anti-inflammatory drugs and 0·65% (59/9117) of those on lumiracoxib reached the cardiovascular endpoint (1·14 [0·78-1·66], p=0·5074). Interpretation Lumiracoxib showed a three to four-fold reduction in ulcer complications compared with non-steroidal anti-inflammatory drugs without an increase in the rate of serious cardiovascular events, suggesting that lumiracoxib is an appropriate treatment for patients with osteoarthritis.
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U2 - 10.1016/S0140-6736(04)16893-1
DO - 10.1016/S0140-6736(04)16893-1
M3 - Article
C2 - 15325831
AN - SCOPUS:4344661128
SN - 0140-6736
VL - 364
SP - 665
EP - 674
JO - The Lancet
JF - The Lancet
IS - 9435
ER -