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P606. Once-daily versus three-times-daily oral budesonide in active Crohn's disease: a double-blind, double-dummy, randomized trial

A. Dignass1, V. Grinevich2, M. Zakharash3, A. Goldis4, L. Jonaitis5, L. Gabalec6, G. Vasileva7, I. Rácz8, B. Pekárková9, J. Derova10, R. Greinwald11, R. Mueller11, 1Agaplesion Markus-Krankenhaus, Dept. of Medicine I, Frankfurt, Germany, 2I.M. Sechenov First Moscow Medical State University, Dept. of Conservative Coloproctology, Moscow, Russian Federation, 3O.O. Bogomolets National Medical University, Chair of surgery No. 1, City Clinical hospital No. 18, Dept. of Proctology, Kiev, Ukraine, 4Algomed Policlinic, Timisoara, Romania, 5Hospital of Lithuanian University of Health Sciences Kaunas Clinics, Dept. of Endoscopy, Kaunas, Lithuania, 6Orlickoústecká nemocnice, a.s., Ústí nad Orlicí, Czech Republic, 7MBAL Rousse, IIIrd Therapeutic Ward – Gastro­enterology  2, Rousse, Bulgaria, 8Petz Aladár Megyei Kórház, I. Belgyógyászat, Györ, Hungary, 9GEA s.r.o, Gastroenterology Department, Trnava, Slovakia, 10Latvian Maritime Medical Centre, Riga, Latvia, 11Dr Falk Pharma GmbH, Dept. of Clinical Research & Development, Freiburg, Germany

Background

Non-adherence to medication intake in IBD is more frequent with multiple dosing regimens compared to once daily (OD) dosing.

Methods

This pivotal study aimed to prove the non-inferiority of 9 mg oral budesonide (Budenofalk®) OD to 3 mg oral budesonide three-times daily (TID) (Budenofalk®) for the treatment of mild-moderately active Crohn's disease. Moreover, the course of induction of clinical remission was to be evaluated.

Patients with mild-moderately active ileo-colonic Crohn's disease (Clinical Disease Activity Index [CDAI] >200 and <400) were eligible for this double-blind, double-dummy, randomized, multicenter, phase III study, which used a group-sequential adaptive design. Patients received 9 mg budesonide OD (n = 238) or 3 mg budesonide TID (n = 233) for 8 weeks. Primary endpoint was the rate of clinical remission (defined by CDAI <150) at week 8 (LOCF) (per protocol [PP] population).

Results

473 patients were randomized, 469 evaluable for safety, 471 for intention-to-treat (ITT), and 439 for PP analysis. The confirmative analysis of the primary endpoint which proved non-inferiority between both treatment regimens is presented in the table.

Moreover, also the course of the induction of clinical remission was identical between both treatments as presented in the figure.

Both treatment regimens were safe and no drug-related serious adverse events were observed.

Figure: Course of clinical remission (CDAI <150) during the study.

Table: Primary efficacy endpoint (confirmative testing at interim analysis)
 Number (%) of patients with clinical remission at week 8 (LOCF)Shifted asymptotic χ2 test for comparing two rates*Difference between proportions** [95% CI]
 9 mg budesonide OD3 mg budesonide TIDp (one-sided) 
PP134/188 (71.3%)142/189 (75.1%)0.01743 (overall)−3.8% [−14.4%, 6.6%]
ITT137/200 (68.5%)143/201 (71.1%)0.00897 (overall)−2.6% [−13.2%, 7.9%]
*Non-inferiority margin: −15%.
**9 mg budesonide OD − 3 mg budesonide TID; asymptotic confidence interval.

Conclusion

Budesonide 9 mg OD was non-inferior to budesonide 3 mg TID for induction of clinical remission in mild-moderately active, ileo-colonic Crohn's disease. Moreover, there was no difference between the treatment regimens with respect to the course of induction of clinical remission, suggesting that OD treatment with budesonide should be used in CD patients to enhance adherence to treatment and further improve its therapeutic efficacy.

Support: Dr. Falk Pharma GmbH, Freiburg, Germany