Enteric-coated budesonide for the induction and maintenance of remission of Crohn’s disease in children

Abstract

Objective: These studies evaluated the safety and efficacy of enteric-coated budesonide for the induction and maintenance of remission of mild-to-moderate Crohn’s disease (CD) in children.

Methods: The consecutive, multicenter, open-label, non-comparative studies enrolled patients aged 6–17 years. In the induction study, patients with active CD of the ileum and/or ascending colon received budesonide 9 mg or 6 mg once daily for 8 weeks; in the maintenance study, patients in remission received budesonide 6 mg once daily for 12 weeks. The primary objective was assessment of safety, including glucocorticosteroid-related side effects and serum cortisol levels. Efficacy was assessed using the Pediatric Crohn’s Disease Activity Index (PCDAI), and health-related quality of life (HRQoL) using the IMPACT-III questionnaire.

Results: In the induction study (n = 108), most adverse events were related to CD, commonly abdominal pain; possible glucocorticosteroid-related effects included acne and increased appetite but without significant weight gain. Subnormal morning cortisol levels were observed in 32 of 103 patients after 8 weeks. Budesonide reduced disease activity from baseline (mean ± standard deviation, 9.1 ± 8.5 vs. 19.1 ± 10.1, p < .001) with 58.1% of patients reaching remission (PCDAI <10); HRQoL improved (p < .001). In the maintenance study (n = 50), mean disease activity worsened (p = .047) with HRQoL unchanged (p = .33).

Conclusions: Budesonide treatment was generally well tolerated, although the potential for adrenal suppression was noted. Budesonide was effective for induction of remission in children with mild-to-moderate CD but not for maintaining remission (ClinicalTrials.gov identifiers: NCT01444092, NCT01453946).

Keywords:

• Cortisol
• inflammatory bowel diseases
• pediatric Crohn’s disease
• pituitary– adrenal system

Note

Transparency

Declaration of funding

This work was supported by AstraZeneca, which has since entered into an agreement with Perrigo for the rights of Entocort in the United States.

Author contributions: S.A.C. took a lead in determining the study concept and design. All authors contributed to analyzing and interpreting the data. T.P. performed the statistical analyses. All authors contributed to drafting the article and revising it critically for important intellectual content, and have given final approval of the submitted version.

Declaration of financial/other relationships

S.A.C. has disclosed that he has served as a consultant for, and has received research support from, AbbVie, AstraZeneca, Janssen, and Nestlé; he has also served as a speaker for Abbvie, Janssen, and Nestlé. K.B. has disclosed that he has served as a speaker for Mylan Pharmaceuticals and Nutricia, and as a consultant on advisory boards for AbbVie, Janssen, and Shire. S.K. has disclosed that she has served as a speaker for AbbVie, Danone, Hipp, Merck Sharp & Dohme, and Nestlé, and as a consultant on advisory boards for AbbVie, Boehringer Ingelheim, Danone, Janssen, Merck, Merck Sharp & Dohme, and Nestlé, and has received research support from Euroimmun, Eurospital, Immundiagnostik, INOVA, Mead Johnson, Merck Sharp & Dohme, Nestlé, R-Biopharm, ThermoFisher, and Schär. P.L. has disclosed that he has served as a speaker for Nestlé and Nutricia, and as a consultant on advisory boards for AbbVie and Hospira. S.E. has disclosed that he is an employee of AstraZeneca. T.P. has disclosed that she is a consultant for, a former employee of, and has ownership interest in AstraZeneca. J.K., M.A., R.A., and R.B. have disclosed that they have no significant relationships with or financial interests in any commercial companies related to this study or article.

CMRO peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Acknowledgments

The authors thank the participants, the centers, and the clinical teams involved in these studies. Medical writing support was provided by Richard Claes PhD and Nesta Hughes PhD from Oxford PharmaGenesis, Oxford, UK, and was funded by AstraZeneca Gothenburg, Mölndal, Sweden.

Notes

*Entocort is a trade name of AstraZeneca AB, Södertälje, Sweden