ONCE-DAILY, ORAL OPC-6535 IN THE TREATMENT OF ACTIVE ULCERATIVE COLITIS

Purpose: OPC-6535 represents a novel thiazole class of IBD medications determined, in part, to inhibit phosphodiesterase (PDE) 4. Its mechanisms of action, which include inhibitory effects on neutrophil and monocyte super-oxide production, cytokine secretion, and endothelial adhesion, are distinct from those of 5-ASA. This offers the potential for use in ulcerative colitis (UC) alone or in combination with 5-ASA therapy. A recent randomized, multi-center, placebo-controlled trial of once daily, oral OPC-6535 (OPC) in subjects with mild to moderate UC demonstrated improvement in mean DAI score and other endpoints. The aim of the current investigation was to compare treatment responses in subjects with and without concomitant 5-ASA use. Methods: 186 subjects were randomized to receive an oral, once daily dose of either 25 mg or 50 mg OPC or placebo for 8 weeks. Eligibility included a new or established diagnosis of UC, flare within 12 weeks, and Disease Activity Index (DAI) score of 4–11 on a scale of 12. Concomitant 5-ASA was permitted if stable for 14 days before entry and throughout the study. Results: Baseline DAI scores were comparable between 5-ASA and non-5-ASA users (mean ± SD: 5-ASA 7.5 ± 1.7 vs non-5ASA 7.2 ± 1.8). 73% of subjects used concomitant 5-ASA (mean dose ± SD: 2.2 ± 1.5 g/d); 27% were above therapeutic dose. Improvement in DAI scores (negative change from baseline) at OPC 25 and 50 mg was similar between 5-ASA users and non-users. The treatment effect of giving OPC 25 or 50 mgto 5-ASA users and non-users was superior to using 5-ASA alone. These differences were even more pronounced in subjects with greater disease severity (DAI 7–11). Conclusions: OPC-6535 shows promise as both primary and adjunctive (to 5-ASA) therapy of UC, especially in subjects with greater disease severity.Table: Mean Change from Baseline in the DAI Score—All subjectsTable: Mean Change from Baseline in the DAI Score—Subjects with DA17-11