SAFETY OF CELECOXIB IN PATIENTS WITH ULCERATIVE COLITIS IN REMISSION

Abstract

Purpose: To compare the incidence of flare and changes in mucosal histology in ulcerative colitis patients in remission who were randomized to receive either celecoxib 200 mg bid or placebo. Methods: This was a multicenter, parallel-group, double-blind study of patients with clinically (total Mayo Clinic score <3) and endoscopically quiescent (Mayo flexible sigmoidoscopy score 0 or 1) ulcerative colitis who were receiving maintenance therapy and who had either present or past history of nonspecific arthritis, arthralgia, or other conditions requiring nonsteroidal anti-inflammatory drug (NSAID) therapy. Patients were randomized to celecoxib 200 mg bid or placebo for 14 days. On Day 14 or early termination, patients underwent repeat flexible sigmoidoscopy (with a mucosal biopsy at US sites), clinical evaluation, laboratory tests, and physical examination. Primary endpoint was the percentage of patients whose disease exacerbated after treatment (flare) defined as a total Mayo Clinic score of ≥ 5 and an increase in Mayo flexible sigmoidoscopy score of ≥ 1 point. Mucosal biopsies were graded for inflammation and expression of immunoreactive COX-2. Results: Celecoxib- (n = 112) and placebo-treated (n = 110) patients had similar baseline characteristics. Of these, 110 celecoxib- and 107 placebo-treated patients had at least 1 dose of study drug, and both sigmoidoscopies and Mayo Clinic scores at baseline and final assessment. The mean change in total Mayo Clinic score in the placebo group was 0.44 compared with 0.28 (P= 0.37) for celecoxib. The incidence of adverse events in each treatment arm further supports the GI safety of celecoxib. In the 107 patients (celecoxib [n = 53] and placebo [n = 54]) who had a biopsy, the majority of specimens were grade 1 (chronic inflammatory filtrate). The change from baseline in histopathology scores in the placebo group reflected an increase in disease severity, while the celecoxib group change showed a slight decrease. Measures of COX-2 expression were similar in both groups at both baseline and final assessments. Conclusions: Celecoxib 200 mg bid for 14 days is as safe as placebo in patients with ulcerative colitis in remission who require NSAID therapy. This was confirmed by clinical, sigmoidoscopic and histopathologic assessments.