P-148 Budesonide MMX Versus Placebo in Patients with Active, Mild-to-Moderate Ulcerative Colitis who Were 5-ASA Naïve or Previously Treated with 5-ASA (2013)

Current guidelines recommend patients with active, mild-to-moderate ulcerative colitis (UC) receive initial therapy with mesalamine (5-ASA), escalating to treatment with systemic steroids and to AZA, 6MP, and biologic therapy as the disease progresses in severity. To achieve remission in one patient with 5-ASA compared with placebo, meta-analyses indicated that the number-needed-to-treat (NNT) (95% CI) is 6 (5,8). It was also demonstrated that treatment with high-dose 5 ASA (>2.5 g/day) compared with standard-dose 5-ASA (2–2.5 g/day) provided a NNT of 25 (13,714) (Ford, Am J Gastroenterol 2011;106:601), suggesting minimal incremental benefit to achieve remission with high-dose compared with standard-dose therapy. Prior post-hoc analyses of the CORE I and CORE II studies demonstrated that budesonide MMX (B-MMX) 9 mg was effective at inducing combined clinical and endoscopic remission and symptom resolution in patients with active, mild-to-moderate UC, regardless of prior 5-ASA use. In this post-hoc analysis, the odds ratio (OR) and NNT for achieving clinical and endoscopic remission and symptom resolution were assessed for B-MMX 9 mg compared with placebo in patients with prior 5-ASA treatment compared with those naïve to 5-ASA. Patients receiving B-MMX 9 mg or placebo as monotherapy were classified as either 5-ASA naïve or previously exposed to 5-ASA. Combined clinical and endoscopic remission at 8 weeks was defined by stringent criteria of UCDAI score ≤1, with sub-scores of 0 for rectal bleeding and stool frequency, no mucosal friability after colonoscopy, and ≥1-point reduction from baseline in endoscopic index score. Symptom resolution was defined as subscores of 0 for both rectal bleeding and stool frequency. A total of 442 patients who received B-MMX 9 mg or placebo in the CORE I and CORE II studies were analyzed. Overall, 146 (33%) patients were 5-ASA naïve and 296 (67%) patients had prior history of 5-ASA use (mean 5-ASA dose was 2.5 g/day), the majority of which (97%) within 30 days of first study drug administration. The OR (95% CI) for B-MMX 9 mg compared with placebo for achieving clinical and endoscopic remission for 5-ASA naïve patients was 6.7 (1.5,30.1) and 2.6 (1.2,5.6) for patients with prior 5-ASA use. The NNT (95% CI) to achieve clinical and endoscopic remission for 5-ASA naïve patients was 7 (5,17) compared with 11 (6,46) for patients with prior 5-ASA exposure (difference ns). The ORs for achieving symptom resolution were 2.4 (1.0,5.9) and 2.1 (1.2,3.7), respectively, with a NNT of 8 (4,77) for 5 ASA naïve patients and 10 (5,50) for patients with prior 5-ASA (difference ns). Treatment-emergent AEs, including potential glucocorticoid effects, occurred with similar frequencies across groups. Once-daily B-MMX 9 mg was well tolerated and effective at inducing combined clinical and endoscopic remission and symptom resolution in patients with active, mild-to-moderate UC, regardless of prior 5-ASA use. Given the high NNT for patients with active UC to achieve remission with high-dose 5-ASA and demonstrated significant benefit of B-MMX in patients naïve to 5-ASA, it is rational to initiate treatment early with B-MMX, both in patients naïve to 5-ASA or those failing standard-dose 5-ASA.