Efficacy and Tolerability of a Once Daily Treatment with Budesonide Capsules Versus Mesalamine Granules for the Treatment of Active Ulcerative Colitis: A Randomized, Double-Blind, Double-Dummy, Multicenter Study

Abstract

Background: Recently, it has been shown in a small pilot trial that budesonide capsules (9mg budesonide once daily [OD]) might be effective for the treatment of active, distal ulcerative colitis.1 AIM: Therefore, this pivotal study aimed to evaluate the efficacy and tolerability of capsules, containing gastric juice-resistant budesonide granules with a pH>6.4 dependent release profile (9mg budesonide OD), versus gastric juice-resistant mesalamine granules with a pH≥6.0 dependent, prolonged release profile (3g mesalamine OD) in patients with active ulcerative colitis. METHODS: Patients with active ulcerative colitis (Clinical Activity Index [CAI] ≥6, Endoscopic Index [EI] ≥4) were eligible for this double-blind, double-dummy, randomized, multicenter, phase III study. Patients received 9mg budesonide OD (n=177) or 3g mesalamine OD (n=166) for 8 weeks. Primary endpoint was clinical remission (CAI≤4, with stool frequency and rectal bleeding subscores of '0') at the final/ withdrawal visit (per protocol (PP) population). RESULTS: 343 patients were randomized, treated and evaluable for safety and intention-to-treat (ITT), 302 for PP analysis. Primary efficacy endpoint: In the PP analysis, 67/153 patients (44%) in the budesonide group and 89/149 (60%) in the mesalamine group achieved clinical remission (p=0.5657 for noninferiority). In the ITT analysis, 70/177 patients (40%) in the budesonide group and 91/ 166 (55%) in the mesalamine group achieved clinical remission (p=0.5203). Both treatment regimens were safe and no drug-related serious adverse events were observed. 3g mesalamine OD showed better efficacy rates in all efficacy endpoints. CONCLUSION: In active ulcerative colitis, treatment with 3g mesalamine OD is superior to a 9mg budesonide OD treatment. Both treatments were safe.