Budesonide Foam for Ulcerative Proctitis (UP) and Ulcerative Proctosigmoiditis (UPS): Subgroup Analyses of 2 Randomized, Placebo-Controlled, Phase 3 Studies (2014)

Introduction: To describe the efficacy of rectally administered budesonide foam (BF) by clinically relevant demographic and baseline characteristics. Methods: Adults with endoscopically confirmed mild-to-moderate UP or UPS with baseline modified Mayo disease activity index (MMDAI) scores ≥5 and ≤10 and subscale ratings ≥2 for rectal bleeding and endoscopic appearance were randomized to BF 2 mg/25 mL or placebo (PBO) twice daily for 2 weeks, then once daily for 4 weeks in 2 identical double-blind, phase 3 studies. The primary endpoint was percentage of patients achieving remission at week 6 (rectal bleeding score=0, endoscopy score ≤1, and improvement/no change from baseline in stool frequency MMDAI subscale score). Key secondary endpoints included percentage of patients achieving rectal bleeding subscale score=0 and percentage of patients achieving endoscopy subscale score ≤1 at week 6. Subgroup analyses of the pooled population were performed for select baseline demographic and disease characteristics. Results: A total of 267 and 279 patients were treated with BF and PBO, respectively. At baseline, 98.6% of 546 patients had a rectal bleeding subscale score ≥2, and all patients had an endoscopy subscale score ≥2; the mean baseline total MMDAI score was 7.9. Remission at week 6 (primary endpoint) occurred significantly more frequently among patients receiving BF than PBO for most subgroups, including patients <45 years (41.0% vs. 22.4%; p=0.0003) or ≥45 years (41.4% vs. 26.6%; p=0.0205), patients with MMDAI scores ≥7 (42.7% vs. 25.3%; p<0.0001), patients with UP (30.6% vs. 16.0%; p=0.0315) or UPS (45.1% vs. 26.9%; p=0.0002), and patients with established disease (41.9% vs. 24.7%; p<0.0001). Subgroups with fewer patients had more variable results. Significant differences favoring BF versus PBO for rectal bleeding score =0 at week 6 were observed in patients <45 years (45.5% vs. 28.2%; p=0.0014) or ≥45 years (51.1% vs. 28.4%; p=0.0004), patients with MMDAI scores ≥7 (49.4% vs. 29.4%, p<0.0001), patients with UP (36.1% vs. 19.8%; p=0.0242) or UPS (52.8% vs. 31.5%; p<0.0001), and patients with established disease (48.1% vs. 29.0%; p<0.0001). Achievement of endoscopy score ≤1 at week 6 favored treatment with BF versus PBO for patients <45 years (57.5% vs. 38.8%; p=0.0014), patients with MMDAI scores ≥7 (55.6% vs. 38.8%; p=0.0002), patients with UPS (58.5% vs. 38.6%; p=0.0001), and patients with established disease (55.8% vs. 40.2%; p=0.0004). Conclusion: Efficacy of BF versus PBO was robust across most subgroups, including patients with MMDAI ≥7, patients with UPS, and patients with established disease. BF may be an alternative to suppositories and enemas for appropriately selected patients with mild-to-moderate disease. Research funded by Salix Pharmaceuticals, Inc. Disclosure - Brian Bosworth: serves as a consultant to and is on the speakers’ bureau for Salix Pharmaceuticals, Inc. William J. Sandborn: serves as a consultant 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. Enoch Bortey: 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.