Analgesic efficacy of celecoxib in postoperative oral surgery pain: A single-dose, two-center, randomized, double-blind, active- and placebo-controlled study

Background: Celecoxib 200 mg has been reported to reduce pain following dental extraction but to offer poorer pain relief than active comparators. Objective: The aim of this study was to compare the efficacy and tolerability of celecoxib 400 mg, the recommended loading dose for treatment of acute pain, with that of ibuprofen 400 mg and placebo following oral surgery. Methods: This was a single-dose, 2-center, randomized, double-blind, active- and placebo-controlled study in which patients with moderate to severe pain following third molar extraction were randomized to receive a single dose of celecoxib 400 mg, ibuprofen 400 mg, or placebo. Pain assessments were completed using a 4-point pain intensity scale where 0 = no pain and 3 = severe pain and a 5-point pain relief scale where 0 = no pain relief and 4 = complete pain relief at baseline and 18 time points over 24 hours. Primary efficacy outcome measures were time to onset of analgesia (the median time to perceptible pain relief in those patients who achieved meaningful pain relief), time-specific pain intensity difference (PID), time-specific pain relief (PR), time-specific sum of PID and PR, and time to use of rescue medication. Times to perceptible and meaningful pain relief (secondary efficacy outcome measures) were recorded using 2 stopwatches. Tolerability was assessed through recording of adverse events, clinical laboratory tests, and physical examinations (including collection of vital signs). Results: One hundred seventy-one patients were randomized to celecoxib 400 mg (30 women and 27 men; mean [SD] age, 21.4 [4.2] years); ibuprofen 400 mg (30 women and 27 men; mean [SD] age, 22.0 [4.7] years); or placebo (34 women and 233 men; mean [SD] age, 21.6 [5.0] years). Mean times to onset of analgesia with celecoxib 400 mg and ibuprofen 400 mg were rapid and comparable (median 28 minutes and 26 minutes, respectively) and were signifi cantly shorter than with placebo (>24 hours) (both, P < 0.05 vs placebo). Compared with placebo, mean time-specific PID scores were significantly greater with celecoxib from 0.5 to 24 hours and with ibuprofen from 0.5 to 16 hours (all, P < 0.05 vs placebo). Time-specific PR scores with celecoxib and ibuprofen were significantly greater from 0.75 and 0.5 hour, respectively, compared with placebo (all, P < 0.05 vs placebo). PID was significantly greater with celecoxib compared with ibuprofen beginning at 11 hours (all, P < 0.05). PR scores were significantly higher with celecoxib versus ibuprofen beginning at 9 hours (all, P < 0.05). Median (95% CI) time to use of rescue medication with celecoxib (>24 hours) was significantly longer than with ibuprofen (10 hours, 58 minutes [8 hours, 30 minutes-14 hours, 34 minutes]) or placebo (I hour, 51 minutes [1 hour, 40 minutes-2 hours, 22 minutes]) (both, P < 0.05). The 3 most common adverse events experienced in the celecoxib group were headache (9 [15.8%] patients), nausea (9 [15.8%] patients), and dizziness (6 [10.5%] patients). Conclusions: In this postsurgical dental pain study, the onset and magnitude of pain relief with celecoxib 400 mg and ibuprofen 400 mg were found to be comparable. In addition, patients who received celecoxib 400 mg as a single dose had a significantly longer time to use of rescue medication and had higher pain relief scores later in the study than those who received ibuprofen 400 mg. Celecoxib was well tolerated compared with placebo.