Improvement in gastrointestinal tolerability of the selective cyclooxygenase (COX)-2 inhibitor, meloxicam, compared with piroxicam: results of the Safety and Efficacy Large-scale Evaluation of COX-inhibiting Therapies (SELECT) trial in osteoarthritis.
SELECT is a large-scale, prospective, international, multicentre, double-blind, double-dummy, randomized, parallel-group trial. Patients with exacerbation of osteoarthritis were treated with the recommended dose of meloxicam (7.5 mg) or piroxicam (20 mg) once daily for 28 days; 4320 patients were administered meloxicam and 4336 piroxicam. The incidence of adverse events was significantly lower in the meloxicam group (22.5%) compared with the piroxicam group (27.9%; P < 0.001), mainly due to the significantly lower incidence of gastrointestinal (GI) adverse events in the meloxicam than in the piroxicam group (10.3% vs 15.4%,; P < 0.001), while the efficacy of both drugs was equivalent. Individual GI events occurred significantly less often with meloxicam than piroxicam: dyspepsia (3.4% vs 5.8%; P < 0.001), nausea/vomiting (2.5% vs 3.4%; P < 0.05) and abdominal pain (2.1% vs 3.6%; P < 0.001). There were 16 patients with perforations, ulcerations or bleeding (PUBs) of the upper GI tract in the piroxicam group compared with seven in the meloxicam group (relative risk piroxicam:meloxicam = 1.4). Four PUBs were complicated (perforations or bleedings); none of these occurred in the meloxicam group (relative risk piroxicam:meloxicam = 1.9). The outcome of SELECT is consistent with that of the large-scale clinical trial of similar design and size which compared 7.5 mg meloxicam with 100 mg diclofenac in patients with osteoarthritis, and with a previous global analysis of the safety of meloxicam. It adds further data to the proposed relationship between selective inhibition of cyclooxygenase-2 and improved GI tolerability of non-steroidal anti-inflammatory drugs.
Division of Rheumatology, University Hospitals, K.U. Leuven, Belgium.
J
J
Dequeker
C
C
Hawkey
A
A
Kahan
K
K
Steinbrück
C
C
Alegre
E
E
Baumelou
B
B
Bégaud
H
H
Isomäki
G
G
Littlejohn
J
J
Mau
S
S
Papazoglou
D000368:Aged; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects* / Q000627:therapeutic use; D016861:Cyclooxygenase Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use; D004311:Double-Blind Method; D005260:Female; D005767:Gastrointestinal Diseases / Q000139:chemically induced*; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors; D008297:Male; D000077239:Meloxicam; D008875:Middle Aged; D010003:Osteoarthritis / Q000188:drug therapy*; D010894:Piroxicam / Q000009:adverse effects* / Q000627:therapeutic use; D011446:Prospective Studies; D013843:Thiazines / Q000009:adverse effects* / Q000627:therapeutic use; D013844:Thiazoles / Q000009:adverse effects* / Q000627:therapeutic use; D016896:Treatment Outcome
D000894:Anti-Inflammatory Agents, Non-Steroidal; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D013843:Thiazines; D013844:Thiazoles; D010894:Piroxicam; D000077239:Meloxicam