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

In Ah Choi, Han-Joo Baek, Chul-Soo Cho, Yeon-Ah Lee, Won Tae Chung, Young Eun Park, Yun Jong Lee, Yong-Beom Park, Jisoo Lee, Shin-Seok Lee, Wan-Hee Yoo, Jung-Soo Song, Seong Wook Kang, Hyun Ah Kim, Yeong Wook Song, In Ah Choi, Han-Joo Baek, Chul-Soo Cho, Yeon-Ah Lee, Won Tae Chung, Young Eun Park, Yun Jong Lee, Yong-Beom Park, Jisoo Lee, Shin-Seok Lee, Wan-Hee Yoo, Jung-Soo Song, Seong Wook Kang, Hyun Ah Kim, Yeong Wook Song

Abstract

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.

Figures

Figure 1
Figure 1
Patient allocation, follow-up, and analysis in the study of pelubiprofen versus celecoxib for the patients with rheumatoid arthritis.aExcluded from safety analysis. a+bExcluded from intention to treat analysis.
Figure 2
Figure 2
Mean pain intensity in patients with rheumatoid arthritis treated with pelubiprofen 30 mg t.i.d. or celecoxib 200 mg b.i.d. as measured using a 100 mm visual analog scale (VAS). Bars represent standard deviations.

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