3g mesalazine granules are superior to 9mg budesonide for achieving remission in active ulcerative colitis: a double-blind, double-dummy, randomised trial

J Crohns Colitis. 2011 Apr;5(2):129-38. doi: 10.1016/j.crohns.2010.11.006. Epub 2010 Dec 14.

Abstract

Background and aims: Budesonide may be an effective therapy for mild-to-moderately active ulcerative colitis (UC). This study aimed to demonstrate non-inferiority for oral 9mg budesonide once daily (OD) versus 3g mesalazine granules OD.

Methods: This was an eight-week randomised, double-blind, double-dummy, multicentre study in which patients with mild-to-moderately active UC, defined as Clinical Activity Index (CAI) ≥6 and Endoscopic Index (EI) ≥4, received budesonide (Budenofalk® 3mg capsules×3) or mesalazine (Salofalk® 1000mg granules×3). The primary endpoint was clinical remission at week 8 (CAI ≤4 with stool frequency and rectal bleeding subscores of "0").

Results: 343 patients were randomised (177 budesonide, 166 mesalazine). Fewer patients achieved the primary endpoint with budesonide versus mesalazine (70/177 [39.5%] versus 91/166 [54.8%]) with a difference in proportions of -15.3% (95% CI [-25.7%, -4.8%]; p=0.520 for non-inferiority). The median time to first resolution of symptoms was 14.0 days (budesonide) and 11.0 days (mesalazine) (hazard ratio 1.19; 95% CI [0.94, 1.51]). Mucosal healing was observed in 54/177 (30.5%) budesonide patients versus 65/166 (39.2%) mesalazine patients, a difference of -8.6% (95% CI [-18.7%, 1.4%]; p=0.093). The incidences of adverse events (budesonide 26.6%, mesalazine 25.3%) and serious adverse events (budesonide 1.7%, mesalazine 1.2%) were similar.

Conclusions: Once-daily 3g mesalazine administered as granules is superior to 9mg budesonide OD administered as capsules for achieving remission in mild-to-moderately active UC. However, it is noteworthy that remission of UC was attained in about 40% of budesonide-treated patients with a rapid onset of resolution.

Trial registration: ClinicalTrials.gov NCT00747110.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Anti-Inflammatory Agents / administration & dosage
  • Anti-Inflammatory Agents / therapeutic use*
  • Anti-Inflammatory Agents, Non-Steroidal / administration & dosage
  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use*
  • Budesonide / adverse effects
  • Budesonide / therapeutic use*
  • Chi-Square Distribution
  • Colitis, Ulcerative / blood
  • Colitis, Ulcerative / drug therapy*
  • Double-Blind Method
  • Female
  • Humans
  • Hydrocortisone / blood
  • Kaplan-Meier Estimate
  • Male
  • Mesalamine / adverse effects
  • Mesalamine / therapeutic use*
  • Middle Aged
  • Remission Induction

Substances

  • Anti-Inflammatory Agents
  • Anti-Inflammatory Agents, Non-Steroidal
  • Mesalamine
  • Budesonide
  • Hydrocortisone

Associated data

  • ClinicalTrials.gov/NCT00747110