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


CONCLUSIONS
Budesonide multimatrix was safe and efficacious for inducing clinical and endoscopic remission for mild to moderate ulcerative colitis refractory to oral mesalamine therapy.
Inflammatory Bowel Disease Center, University of Chicago Medicine, Chicago, IL, USA.
David T
DT
Rubin
Inflammatory Bowel Disease Center, University of Chicago Medicine, Chicago, IL, USA.
Russell D
RD
Cohen
Division of Gastroenterology, University of California [UC] San Diego and UC San Diego Health System, San Diego, CA, USA.
William J
WJ
Sandborn
Division of Gastroenterology, Perelman School of Medicine of the University of Pennsylvania, Philadelphia, PA, USA.
Gary R
GR
Lichtenstein
Toronto Digestive Disease Associates, Toronto, ON, Canada.
Jeffrey
J
Axler
Department of Pathology and Laboratory Medicine, Mt Sinai Hospital, Toronto, ON, Canada.
Robert H
RH
Riddell
Salix Pharmaceuticals, Raleigh, NC, USA.
Cindy
C
Zhu
Salix Pharmaceuticals, Raleigh, NC, USA.
Andrew C
AC
Barrett
Salix Pharmaceuticals, Raleigh, NC, USA.
Enoch
E
Bortey
Salix Pharmaceuticals, Raleigh, NC, USA.
William P
WP
Forbes
D000328:Adult; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use; D019819:Budesonide / Q000008:administration & dosage / Q000627:therapeutic use*; D003093:Colitis, Ulcerative / Q000188:drug therapy* / Q000473:pathology; D003113:Colonoscopy; D003692:Delayed-Action Preparations / Q000627:therapeutic use; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D057194:Intention to Treat Analysis; D008297:Male; D019804:Mesalamine / Q000627:therapeutic use; D008875:Middle Aged; D012074:Remission Induction; D019233:Retreatment; D012720:Severity of Illness Index
D000893:Anti-Inflammatory Agents; D000894:Anti-Inflammatory Agents, Non-Steroidal; D003692:Delayed-Action Preparations; D019804:Mesalamine; D019819:Budesonide; D006854:Hydrocortisone
Ulcerative colitis; clinical trials; inflammation; inflammatory bowel disease