Gastroenterology

Gastroenterology

Volume 140, Issue 2, February 2011, Pages 425-434.e1
Gastroenterology

Clinical—Alimentary Tract
Budesonide 9 mg Is at Least as Effective as Mesalamine 4.5 g in Patients With Mildly to Moderately Active Crohn's Disease

https://doi.org/10.1053/j.gastro.2010.11.004Get rights and content

Background & Aims

Comparative data on budesonide vs mesalamine for the treatment of mild-to-moderately active Crohn's disease (CD) are sparse. We assessed the efficacy and safety of each therapy in patients with mildly to moderately active CD.

Methods

We performed a randomized, double-blind, double-dummy, 8-week, multicenter study in which 309 patients with mildly to moderately active CD received pH-modified-release oral budesonide (9 mg/day once daily or 3 mg/day 3 times daily) or Eudragit-L–coated oral mesalamine (4.5 g/day).

Results

The primary efficacy variable, clinical remission (defined as Crohn's Disease Activity Index ≤150), at the final visit occurred in 69.5% (107 of 154) of patients given budesonide vs 62.1% (95 of 153) of patients given mesalamine (difference, 7.4%; 95% repeated confidence interval, −4.6% to 18.0%; P = .001 for noninferiority). Clinical remission rates did not differ significantly between the 2 budesonide groups. Treatment response, defined as Crohn's Disease Activity Index of 150 or less and/or a decrease of 70 or more (Δ70) or 100 or more (Δ100) points from baseline to final visit, did not differ significantly between patients given budesonide vs mesalamine (Δ70, P = .11; Δ100, P = .15), or between the 2 budesonide groups (Δ70, P = .38; Δ100, P = .78). No other efficacy end points differed significantly between groups. Discontinuation because of adverse events occurred in 3% and 5% of budesonide- and mesalamine-treated patients, respectively. There were no clinically relevant differences in adverse events between the 2 budesonide groups.

Conclusions

Budesonide (9 mg/day) was numerically, but not statistically, more effective than Eudragit-L–coated mesalamine (4.5 g/day) in patients with mildly to moderately active CD. Budesonide (9 mg/day), administered once daily, was as effective as the standard (3 times daily) regimen.

Section snippets

Study Design and Conduct

This was a double-blind, double-dummy, randomized, active-controlled, 8-week, phase III study conducted during the period from November 2004 to May 2008 at 46 gastroenterology centers in 7 countries (Croatia, Czech Republic, Germany, Greece, Hungary, Israel, Slovak Republic). In this 3-arm trial, patients were randomized (1:1:2 ratio) to receive budesonide (Budenofalk 3-mg capsules; Dr. Falk Pharma GmbH, Freiburg, Germany) at an oral dose of either 3 × 3 mg/day or 1 × 9 mg/day, or oral

Patient Population

In total, 311 patients were recruited (Figure 1). Two patients randomized to budesonide 3 mg, 3 times a day, took no verum study medication and were not evaluable. The remaining 309 patients formed the safety population (79 budesonide 3 mg 3 times a day, 77 budesonide 9 mg OD, and 153 mesalamine). Two patients randomized to budesonide had baseline CDAI of less than 150 and were excluded from the ITT population (78 budesonide 3 mg, 3 times a day, 76 budesonide 9 mg OD, and 153 mesalamine).

Discussion

The results of this double-blind, double-dummy, multicenter trial show that budesonide 9 mg/day (3-mg capsules) is significantly noninferior to mesalamine 4.5 g/day (500-mg tablets) for inducing remission in patients with mildly to moderately active CD within the predefined 10% noninferiority margin. The results indicate that high-dose Eudragit-L–coated mesalamine is associated with a very high rate of remission in mildly to moderately active CD (62% in the ITT population). As anticipated,

Acknowledgments

The authors give special thanks to P. Heine and R. Schwarz (medicomp GmbH, Planegg, Germany) for their assistance in conducting the clinical trial. The authors would like to thank all patients and investigators for their participation and contribution to the study.

Editorial assistance, comprising revision and finalization of the draft manuscript prepared by the authors, was provided by freelance writer Caroline Dunstall, with funding from Dr. Falk Pharma GmbH.

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    This article has an accompanying continuing medical education activity on page e13. Learning Objective: Upon completion of this exam, successful learners will be able to identify patients with mild to moderately active Crohn's disease for the treatment with either mesalamine or budesonide.

    Conflicts of interest The authors disclose the following: Andreas Tromm has received speaker's honoraria and travel funding from Dr Falk Pharma GmbH; Karin Dilger, Ralf Mohrbacher, and Roland Greinwald are employees of Dr Falk Pharma GmbH. The remaining authors disclose no conflicts.

    Funding The study was funded by Dr. Falk Pharma GmbH, Freiburg, Germany. The study sponsor contributed to the design of the study in collaboration with the authors, funded the analysis of the data by an independent biostatistics company, and worked in conjunction with the authors to interpret the data. The sponsor was not involved in data collection. ES was supported by the Robert-Bosch Foundation, Stuttgart, Germany and from the Federal Ministry for Education and Research (BMBF, Berlin, Germany; 03 IS 2061C).

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