Michael Huang

Once-Daily Budesonide MMX® Extended-Release Tablets Induce Remission in Patients With Mild to Moderate Ulcerative Colitis: Results From the CORE I Study

BACKGROUND & AIMS Budesonide is a corticosteroid with minimal systemic corticosteroid activity due to first-pass hepatic metabolism. Budesonide MMX® is a once-daily oral formulation of budesonide that extends budesonide release throughout the colon using multi-matrix system (MMX) technology. METHODS We performed a randomized, double-blind, double-dummy, placebo-controlled trial to evaluate the efficacy of budesonide MMX for induction of remission in 509 patients with active, mild to moderate ulcerative colitis (UC). Patients were randomly assigned to groups that were given budesonide MMX (9 mg or 6 mg), mesalamine (2.4 g, as reference), or placebo for 8 weeks. The primary end point was remission at week 8. RESULTS The rates of remission at week 8 among subjects given 9 mg or 6 mg budesonide MMX or mesalamine were 17.9%, 13.2%, and 12.1%, respectively, compared with 7.4% for placebo (P = .0143, P = .1393, and P = .2200). The rates of clinical improvement at week 8 among patients given 9 mg or 6 mg budesonide MMX or mesalamine were 33.3%, 30.6%, and 33.9%, respectively, compared with 24.8% for placebo (P = .1420, P = .3146, and P = .1189). The rates of endoscopic improvement at week 8 among subjects given 9 mg or 6 mg budesonide MMX or mesalamine were 41.5%, 35.5%, and 33.1%, respectively, compared with 33.1% for placebo. The rates of symptom resolution at week 8 among subjects given 9 mg or 6 mg budesonide MMX or mesalamine were 28.5%, 28.9%, and 25.0%, respectively, compared with 16.5% for placebo (P = .0258, P = .0214, and P = .1025). Adverse events occurred at similar frequencies among groups. CONCLUSIONS Budesonide MMX (9 mg) was safe and more effective than placebo in inducing remission in patients with active, mild to moderate UC.

Induction of clinical and colonoscopic remission of mild-to-moderate ulcerative colitis with budesonide MMX 9 mg: pooled analysis of two phase 3 studies.

Conventional oral corticosteroids are effective at reducing inflammation associated with ulcerative colitis (UC); however, systemic adverse effects limit their use. Budesonide MMX is an extended‐release, second‐generation corticosteroid that targets delivery of budesonide to the entire colon.

Budesonide MMX for the Induction of Remission of Mild to Moderate Ulcerative Colitis: A Pooled Safety Analysis

Background and aims: Cumulative safety and tolerability of budesonide MMX, a once-daily oral corticosteroid for inducing mild to moderate ulcerative colitis remission, was examined. Methods: Data from three randomized, double-blind, placebo-controlled, phase II or III studies [budesonide MMX 9mg, 6mg, or 3mg for 8 weeks]; one phase II study [randomisation to budesonide MMX 9mg or placebo for 4 weeks, then open-label budesonide MMX 9mg for 4 weeks]; and one open-label study [budesonide MMX 9mg for 8 weeks] were pooled. Results: Patients randomised to budesonide MMX 9mg [n = 288], 6mg [n = 254], or placebo [n = 293] had similar rates of adverse events [AEs] [27.1%, 24.8%, and 23.9%, respectively] and serious AEs [2.4%, 2.0%, and 2.7%, respectively]; treatment-related AEs and serious AEs were reported by 11.8% and 13.5%, and 5.9% and 2.2%, respectively, of patients receiving budesonide MMX 3mg [n = 17] or open-label budesonide MMX 9mg [n = 89]. Mean morning plasma cortisol concentrations were normal from baseline to final visit across randomised groups; in patients receiving open-label budesonide, mean cortisol concentration was 129.9 nmol/l after 4 weeks, returning to normal concentrations at final visit. Budesonide MMX was not associated with an overall increased risk for glucocorticoid-related adverse effects. Conclusions: Budesonide MMX 9mg was associated with normal mean cortisol concentrations at final visit and an AE incidence comparable to placebo. Overall, budesonide MMX was safe and well tolerated for inducing remission of patients with mild to moderate ulcerative colitis.

Bioavailability profile of Uceris MMX extended-release tablets compared with Entocort EC capsules in healthy volunteers.

Objective To compare the pharmacokinetics of the extended-release MMX® formulation of budesonide (Uceris®) with that of Entocort® EC, an extended (controlled ileal) release formulation of budesonide. Methods Using an open-label, randomized, three-period crossover, Latin square design, healthy male or female volunteers received single doses of 6 mg Uceris®, 9 mg Uceris® or 9 mg Entocort® EC. Standard pharmacokinetic parameters were assessed. Results The study included 12 subjects. The 9 mg Uceris® and 9 mg Entocort® EC formulations had comparable area under the concentration–time curve (AUC) data, but 9 mg Uceris® had a notably longer time to first appearance in plasma (median Tlag, 6 h versus 1 h, respectively), and a delayed time to maximum concentration (median Tmax, 15 h versus 5 h, respectively) compared with 9 mg Entocort® EC. The ratio of log-transformed AUC0–last (Uceris®/Entocort® EC) was 91% (90% confidence interval [CI] 77%, 108%) and the corresponding maximum concentration ratio was 79% (90% CI 63%, 100%). Conclusion Uceris was associated with a similar extent (AUC) of systemic exposure to budesonide compared with that following Entocort. However, for Uceris, the pharmacokinetic profile was delayed, a pattern consistent with greater colonic delivery of the active substance.

Tu1252 Effect of Budesonide MMx 6 mg on the Hypothalamic-Pituitary-Adrenal (HPA) Axis in Patients With Ulcerative Colitis: Results From a Phase III, 12 Month Safety and Extended use Study

follow-up time from first biologic 4.5 years (IQR 1.4-7.6). 1751 IFX infusions were given, with increasing frequency over time reflecting the shift from episodic to maintenance therapy. Infusion number increased by 202.6% between 2004-5 and 143 patients commenced maintenance anti-TNF from 2005-11, in contrast with only 14 up to 2005. Median time from diagnosis to first anti-TNF was 97 months up to 2005, falling to 52 months from 200611. Of 72 CD patients treated with ADA, 37 required dose escalation to weekly, at a median interval of 6 months (median 29.5 months follow-up). No anti-TNF naive patients required dose escalation, but 12/18 patients starting ADA due to secondary loss of response to IFX required weekly therapy (66.7%). There were 238 hospital admissions (93 for disease flares) in the year preceding anti-TNF therapy, falling to 197 admissions (35 for disease flares) in the year after treatment initiation. Faecal calprotectin (FC) before and 3 months after starting anti-TNF was available for 22 patients; this fell by a median of 470.5 mcg/g. 39 infusion reactions were observed in 35 IFX-treated patients; 6 followed a treatment break of 1471568 days. 8 serum sickness-like reactions were observed following IFX, and 2 with ADA. Conclusion: Outcome of changes in treatment patterns will inform unanswered questions regarding patient selection and length of therapy. Drug holiday from IFX remains an indication for ADA. Innovations in monitoring response to anti-TNF therapy, notably recording of HBI and FC before every treatment (initiated in our centre during 2011) will further aid decision-making.