Efficacy and tolerability of lumiracoxib in the treatment of osteoarthritis of the knee: a 13-week, randomized, double-blind comparison with celecoxib and placebo.
BACKGROUND
Lumiracoxib is a cyclooxygenase-2-selective inhibitor developed for the treatment of osteoarthritis (OA), rheumatoid arthritis, and acute pain.


OBJECTIVE
This study assessed the efficacy and tolerability of lumiracoxib 100 mg QD compared with celecoxib and placebo in patients with OA of the knee.


METHODS
In this 13-week, double-blind, double-dummy,placebo-controlled, parallel-group study, patients with primary OA of the knee and pain intensity in the target knee a 40 mm on a 100-mm visual analog scale after a 3- to 7-day washout of nonsteroidal anti-inflammatory drugs were randomized to receive lumiracoxib 100 mg QD, lumiracoxib 100 mg QD with a loading dose of lumiracoxib 200 mg QD for the first 2 weeks, celecoxib 200 mg QD, or placebo. Three primary efficacy variables were assessed at the end of the study: pain intensity in the target knee, the patient's global assessment of disease activity, and functional status (Western Ontario and McMaster Universities Osteoarthritis Index total score). In addition, the treatment response was assessed using the Outcome Measures in Clinical Trials-Osteoarthritis Research Society International (OMERACT OARSI) criteria. The safety profile and tolerability of all treatments were also examined.


RESULTS
The study enrolled 1551 patients (primarily white; 62% female; mean age, 60.5 years): 391 were randomized to receive lumiracoxib 100 mg QD, 385 lumiracoxib 100 mg QD with a loading dose, 393 celecoxib 200 mg QD, and 382 placebo. Treatment groups were closely balanced at baseline with respect to demographic and disease characteristics. Lumiracoxib was superior to placebo (P < 0.001) and similar to celecoxib on all primary efficacy variables. Reductions in pain intensity in the target knee were similar in the 2 lumiracoxib groups at week 13 (estimated least square mean difference vs placebo: -6.7 and -8.1 mm for lumiracoxib 100 mg QD and lumiracoxib 100 mg QD with loading dose, respectively; both, P < 0.001); with celecoxib, the estimated least square mean difference was -5.7 mm (P < 0.001). Significant differences compared with placebo were seen in all variables starting at week 2 for all active treatments (all, P < 0.001). No significant differences were seen between the lumiracoxib groups at any time point. Based on OMERACT OARSI criteria, all active treatments were superior to placebo (all, P < 0.001). Lumiracoxib and celecoxib were well tolerated, with an incidence of adverse events similar to that with placebo (64.7% lumiracoxib 100 mg QD, 67.0% lumiracoxib 100 mg QD with loading dose, 58.8% celecoxib, 58.4% placebo).


CONCLUSIONS
In this population of patients with OA of the knee, lumiracoxib 100 mg QD was of similar efficacy to celecoxib 200 mg QD and had similar tolerability to placebo.
Sheldon
Eric
E
Miami Research Associates, Miami, Florida 33173, USA. rericsheldon@hotmail.com
Beaulieu
Andre
A
Paster
Zorba
Z
Dutta
Dipen
D
Yu
Sue
S
Sloan
Victor S
VS
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000068579:Celecoxib; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D004008:Diclofenac / Q000031:analogs & derivatives; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008565:Membrane Proteins; D008875:Middle Aged; D009930:Organic Chemicals / Q000009:adverse effects / Q000627:therapeutic use*; D020370:Osteoarthritis, Knee / Q000188:drug therapy*; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D011720:Pyrazoles / Q000009:adverse effects / Q000627:therapeutic use*; D013449:Sulfonamides / Q000009:adverse effects / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome
D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D008565:Membrane Proteins; D009930:Organic Chemicals; D011720:Pyrazoles; D013449:Sulfonamides; D004008:Diclofenac; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D000068579:Celecoxib; C473384:lumiracoxib