Elsevier

The Journal of Pediatrics

Volume 163, Issue 5, November 2013, Pages 1347-1353.e1
The Journal of Pediatrics

Original Article
Budesonide versus Prednisone with Azathioprine for the Treatment of Autoimmune Hepatitis in Children and Adolescents

https://doi.org/10.1016/j.jpeds.2013.05.042Get rights and content

Objective

To compare the effect of budesonide vs prednisone therapy both in combination with azathioprine in pediatric patients with autoimmune hepatitis (AIH).

Study design

Forty-six patients with AIH (11 males and 35 females) aged 9-17 years were enrolled in a 6-month, prospective, double-blind, randomized, active-controlled, multicenter phase IIb study evaluating budesonide (n = 19; 3 mg twice or 3 times daily) vs prednisone (n = 27; 40 mg/day tapered to 10 mg/day), both with azathioprine (1-2 mg/kg/day), followed by a further 6 months of open-label budesonide therapy. The primary efficacy endpoint was complete biochemical remission (normal serum alanine aminotransferase and aspartate aminotransferase levels) without predefined steroid-specific side effects.

Results

We observed no statistically significant difference in the percentage of patients who met the primary endpoint between the budesonide (3 of 19; 16%) and prednisone groups (4 of 27; 15%) after 6 months, nor in the percentage of patients who experienced biochemical remission (budesonide, 6 of 19 [32%]; prednisone, 9 of 27 [33%]), lack of steroid-specific side effects (budesonide, 10 of 19 [53%]; prednisone, 10 of 27 [37%]). The mean weight gain was 1.2 ± 3.5 kg in the budesonide group and 5.1 ± 4.9 kg in the prednisone group (P = .006). A total of 42 patients received open-label budesonide treatment for another 6 months. After 12 months, 46% of these patients achieved complete remission.

Conclusion

Oral budesonide with azathioprine can induce and maintain remission in pediatric patients with AIH and may be considered an alternative therapy to prednisone. The treatment causes fewer side effects and does not lead to weight gain; however, it may be less effective than prednisone in inducing remission.

Section snippets

Methods

Patients with AIH aged 9-17 years were included in this analysis. The diagnosis of AIH was established according to the criteria of the International Autoimmune Hepatitis Group.25 Patients enrolled in the study had either a first diagnosis of acute AIH or had experienced a relapse of previously diagnosed AIH based on liver biopsy analysis performed within 12 months before screening. Patients had serum alanine aminotransferase (ALT) and/or serum aspartate aminotransferase (AST) levels at least

Results

Of the 208 patients enrolled in the study, 46 completed segment A and were evaluable (the intention to treat analysis group). This group comprised 11 males and 35 females, aged 9-17 years at screening (mean ± SD, 13.8 ± 2.2 years) and at age 4-14 years at diagnosis of AIH (mean, 11.8 ± 2.7 years). Segment B was completed by 18 of 19 patients in the budesonide group and by 24 of 27 patients in the prednisone group.

The proportion of females was lower in the budesonide group compared with the

Discussion

For decades, the management of AIH was based on prednisone alone or in combination with azathioprine in adults26, 27, 28, 29 and children.30 The definition of AIH remission varies among studies, and may involve clinical, biochemical, immunologic, and histological status assessment. Alvarez et al14 defined AIH remission as normal serum ALT, and Cuarterolo et al15 defined it as normal ALT in the absence of clinical symptoms. The outcome measure used by Aw et al18 was normalized serum AST

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      While being an option for remission induction, budesonide is more difficult to taper due to its short half-life and limited dose availability on the market. Both prednisolone and budesonide can cause considerable long-term side effects, and in view of the better long-term effectiveness of systemic immunosuppressants, steroids should in any case not be the mainstay of therapy in AIH.27,57,58 Nonetheless, in patients intolerant to azathioprine, and also intolerant to MMF, steroid monotherapy may be a valid treatment alternative, if bone mineral density is good and remains good, and if the prednisolone dose required can be kept at a maximum of 10 mg/day (in children probably at a maximum of 2.5–5 mg/day).

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    Supported by Dr Falk Pharma (BUC-38/AIH). M.P. is employed by Dr Falk Pharma. M.M. is a consultant to Dr Falk Pharma and receives grant support and lecture fees. The other authors declare no conflicts of interest.

    Registered with ClinicalTrials.gov: NCT 00838214.

    A list of members of European AIH-Budesonide Study Group is available at www.jpeds.com (Appendix).

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