Comparison of the efficacy and safety profiles of a pelubiprofen versus celecoxib in patients with rheumatoid arthritis: a 6-week, multicenter, randomized, double-blind, phase III, non-inferiority clinical trial.
BACKGROUND
Pelubiprofen is a prodrug of 2-arylpropionic acid with relatively selective effects on cyclooxygenase-2 activity. The aim of this study was to compare the efficacy and safety profiles of pelubiprofen with those of celecoxib in patients with rheumatoid arthritis.


METHODS
This was a 6-week, multicenter, randomized, double-blind, double-dummy, parallel-group, phase III, non-inferiority clinical trial. The primary end point was non-inferiority of pain decrease from baseline to week-6 as determined using a 100 mm pain visual analog scale (VAS). Pelubiprofen was considered non-inferior to celecoxib if the lower limit of the 97.5% confidence interval for treatment difference [(pain reduction in pelubiprofen group) - (pain reduction in celecoxib group)] was more than -10 mm. The secondary end points were as follows: non-inferiority of (1) reduction of Korean health assessment questionnaire (KHAQ) score; (2) decreased duration of morning stiffness; and (3) decrease in the frequency and total dose of rescue drugs after 6 weeks of treatment.


RESULTS
Seventy-seven patients in the pelubiprofen group and 68 patients in the celecoxib group started the study medication. Pelubiprofen was non-inferior to celecoxib with regard to reduction in VAS pain severity (difference, mean ± SD 5.0 ± 20.1; 97.5% CI, -2.3 to ∞). Pelubiprofen was also non-inferior to celecoxib in terms of the secondary end points, such as, decrease in KHAQ score (0.0 ± 0.5, 97.5% CI -0.2 to ∞), decrease in duration of morning stiffness (median 0.0 minute in both groups), and decrease in the frequency (0.7 ± 3.5, 97.5% CI -0.6 to ∞) and total amount (0.7 ± 3.6, 97.5% CI -0.6 to ∞) of rescue medication uses during the 6 week study period. Safety analysis revealed 31.2% patients in the pelubiprofen group and 20.6% patients in the celecoxib group experienced an adverse drug reaction (ADR). The frequency of gastrointestinal ADRs was 20.8 % and 8.8%, respectively.


CONCLUSIONS
Pelubiprofen was found to be as effective as celecoxib at pain reduction and for relieving stiffness in RA patients. However, more patients in the pelubiprofen group experienced ADR and the frequency of gastrointestinal ADRs was higher in the pelubiprofen group. ClinialTrials.gov identifier: NCT01781702.
In Ah
IA
Choi
Han-Joo
HJ
Baek
Chul-Soo
CS
Cho
Yeon-Ah
YA
Lee
Won Tae
WT
Chung
Young Eun
YE
Park
Yun Jong
YJ
Lee
Yong-Beom
YB
Park
Jisoo
J
Lee
Shin-Seok
SS
Lee
Wan-Hee
WH
Yoo
Jung-Soo
JS
Song
Seong Wook
SW
Kang
Hyun Ah
HA
Kim
Division of Rheumatology, Department of Internal Medicine, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul 110-744, South Korea. ysong@snu.ac.kr.
Yeong Wook
YW
Song
D000328:Adult; D000368:Aged; D001172:Arthritis, Rheumatoid / Q000175:diagnosis* / Q000188:drug therapy*; D000068579:Celecoxib; D052246:Cyclooxygenase 2 Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D004311:Double-Blind Method; D004487:Edema / Q000139:chemically induced; D005260:Female; D005767:Gastrointestinal Diseases / Q000139:chemically induced; D006801:Humans; D008297:Male; D008875:Middle Aged; D010147:Pain Measurement / Q000187:drug effects / Q000379:methods; D010666:Phenylpropionates / Q000009:adverse effects / Q000627:therapeutic use*; D011720:Pyrazoles / Q000009:adverse effects / Q000627:therapeutic use*; D013449:Sulfonamides / Q000009:adverse effects / Q000627:therapeutic use*; D013997:Time Factors
D052246:Cyclooxygenase 2 Inhibitors; D010666:Phenylpropionates; D011720:Pyrazoles; D013449:Sulfonamides; C040375:pelubiprofen; D000068579:Celecoxib