Budesonide Multimatrix Is Efficacious for Mesalamine-refractory, Mild to Moderate Ulcerative Colitis: A Randomised, Placebo-controlled Trial

Abstract

Background and Aims:Safety and efficacy of budesonide multimatrix, an oral extended-release second-generation corticosteroid designed for targeted delivery throughout the colon, were examined for induction of remission in patients with mild to moderate ulcerative colitis refractory to baseline mesalamine therapy.Methods:A randomised, double-blind, placebo-controlled, multicentre trial evaluated efficacy and safety of budesonide multimatrix for induction of remission [ulcerative colitis disease activity index score ≥ 4 and ≤ 10] in 510 adults randomised to once-daily oral budesonide multimatrix 9 mg or placebo for 8 weeks. Patients continued baseline treatment with oral mesalamine ≥ 2.4 g/day.Results:Combined clinical and endoscopic remission at Week 8 was achieved by 13.0% and 7.5% of patients receiving budesonide multimatrix [n = 230] or placebo [n = 228], respectively, in the modified intention-to-treat population [p = 0.049]. Clinical remission [ulcerative colitis disease activity index rectal bleeding and stool frequency subscale scores of 0] was similar in both groups [p = 0.70]. More patients receiving budesonide multimatrix vs placebo achieved endoscopic remission [ulcerative colitis disease activity index mucosal appearance subscale score of 0; 20.0% vs 12.3%; p = 0.02] and histological healing [27.0% vs 17.5%; p = 0.02]. Adverse event rates were similar [budesonide multimatrix, 31.8%; placebo, 27.1%]. Mean morning cortisol concentrations decreased at Weeks 2, 4, and 8 with budesonide multimatrix but remained within the normal range.Conclusion:Budesonide multimatrix was safe and efficacious for inducing clinical and endoscopic remission for mild to moderate ulcerative colitis refractory to oral mesalamine therapy.

Comparative safety of systemic and low‐bioavailability steroids in inflammatory bowel disease: Systematic review and network meta‐analysis

“…The full text was read, and the bibliographies were checked. We initially identified 27 RCTs eligible for inclusion in the Network . Four additional eligible studies were identified in regulatory authorities' drug assessment reports , for a total of 31 trials (Table ).…”

“…Twenty‐seven RCTs comparing budesonide to placebo ( n = 13), budesonide MMX to placebo ( n = 5), prednisone/prednisolone to placebo ( n = 2), beclomethasone dipropionate to placebo ( n = 2), budesonide to budesonide MMX ( n = 1), prednisone/prednisolone to budesonide ( n = 5), and prednisone/prednisolone to beclomethasone dipropionate ( n = 1) were analysed (Table , and Figure A).…”

“…To assess the comparative safety profiles distinguishing the short‐term from the long‐term side effects, we also performed subgroup analyses using a cut‐off of 12 weeks for separating studies of short duration (up to 12 weeks) from those of long duration (over 12 weeks) (Table ).…”

Oral budesonide in gastrointestinal and liver disease: A practical guide for the clinician

“…Mesalazine has the advantage of being suitable for maintenance of remission. In mesalazine‐refractory mild to moderate UC, MMX budesonide has a limited effect on combined clinical and endoscopic remission versus placebo, but no effect on clinical remission alone …”

“…Optimising therapy with budesonide S Miehlke et al Optimising therapy with budesonide endoscopic remission versus placebo, but no effect on clinical remission alone. 55 Maintenance therapy. Budesonide is not recommended or licensed for use as maintenance therapy to prevent relapse in UC.…”