Efficacy and Tolerability of Budesonide Foam With or Without Baseline 5-Aminosalicylic Acid Use in Patients With Ulcerative Proctitis (UP) or Ulcerative Proctosigmoiditis (UPS): Results of 2 Randomized, Placebo-Controlled, Phase 3 Studies (2014)

Introduction: Budesonide foam (BF) is a rectally administered second-generation corticosteroid, designed to optimize drug retention and provide uniform delivery of budesonide for treating distal forms of ulcerative colitis (UC). The current analyses of two phase 3 studies evaluated the impact of baseline oral 5-aminosalicylic acid (ASA) on the efficacy and safety of BF. Methods: Data were pooled from 2 identical multicenter, randomized, double-blind, placebo (PBO)-controlled, phase 3 studies evaluating patients with mild-to-moderate active UP or UPS who received BF 2 mg/ 25 mL twice daily for 2 weeks followed by 2 mg/ 25 mL once daily for 4 weeks or PBO. Patients could continue on a stable oral 5-ASA regimen up to 4.8 g/day. Rectal 5-ASA was not permitted during the studies. Subgroup analyses for the primary endpoint (percentage of patients achieving remission at week 6 [endoscopy score ≤1, rectal bleeding score of 0, and improvement or no change from baseline in stool frequency modified Mayo disease activity index (MMDAI) subscale score]), key secondary endpoints (percentage of patients achieving rectal bleeding MMDAI subscale score=0 and the percentage of patients achieving endoscopy MMDAI subscale score ≤1 at week 6), and safety (monitoring of adverse events [AEs]) were performed for patients who did or did not use an oral 5-ASA at baseline. Results: Of the patients in the pooled BF (n=267) and placebo groups (n=279), 147 (55.1%) and 154 (55.2%) patients, respectively, reported baseline 5-ASA use. Significant treatment effects favoring BF were demonstrated with patients who did or did not use 5-ASA at baseline in remission achievement and rectal bleeding MMDAI subscale scores of 0 (Table). Patients who did not use a baseline 5-ASA had a significant treatment effect for achieving endoscopy MMDAI subscale scores ≤1; however, this difference was not significant for patients who used a baseline 5-ASA. Across all 3 efficacy endpoints, response rates in the BF group were similar within the 2 subgroups: the treatment effect favoring BF was more pronounced in patients who did not use a 5-ASA at baseline versus those who did because of higher placebo response rates in the baseline 5-ASA use population. The incidences of common AEs were generally comparable across subgroups. Conclusion: BF was generally well tolerated and provided a significant treatment benefit versus placebo for mild-to-moderate, distal forms of UC, irrespective of baseline oral 5-ASA use. Research funded by Salix Pharmaceuticals, Inc. Disclosure - William J Sandborn: serves as a consultant for Salix Pharmaceuticals, Inc. Brian Bosworth: serves as a consultant to and is on the speakers’ bureau for Salix Pharmaceuticals, Inc. David T. Rubin: receives grant/research support from AbbVie; Elan Corporation; Prometheus Laboratories Inc.; Shire plc; and Warner Chilcott; serves as a consultant to AbbVie; Bristol-Myers Squibb; Janssen Biotech, Inc.; Elan Corporation; Emmi Solutions; Given Imaging Ltd.; Ironwood Pharmaceuticals; Prometheus Laboratories Inc.; Takeda Pharmaceuticals, Inc.; Telsar Pharma Inc.; UCB Pharma; and Vertex Pharmaceuticals, Inc.; and holds a management position with Cornerstones Health, Inc. Jing Yu: is an employee of and holds stock in Salix Pharmaceuticals, Inc. Andrew C. Barrett: is an employee of and holds stock in Salix Pharmaceuticals, Inc. Craig Paterson: is an employee of and holds stock in Salix Pharmaceuticals, Inc. William P. Forbes: is an officer and employee of and holds stock in Salix Pharmaceuticals, Inc. This research was supported by an industry grant from Salix Pharmaceuticals, Inc.Table 1: Efficacy of Budesonide Foam by 5-ASA Use