Budesonide induces remission more effectively than prednisone in a controlled trial of patients with autoimmune hepatitis

Michael P. Manns, Marek Woynarowski, Wolfgang Kreisel, Yoav Lurie, Christian Rust, Elimelech Zuckerman, Matthias J. Bahr, Rainer Gnther, Rolf W. Hultcrantz, Ulrich Spengler, Ansgar W. Lohse, F. Szalay, Martti Frkkil, Markus Prls, Christian P. Strassburg

Research output: Article

230 Citations (Scopus)

Abstract

Background & Aims Autoimmune hepatitis (AIH) is a chronic liver disease associated with cirrhosis and liver failure. Corticosteroid therapy induces long-term remission but has many side effects. We compared the effects of budesonide (a steroid that is rapidly metabolized, with low systemic exposure) and prednisone, both in combination with azathioprine. Methods We performed a 6-month, prospective, double-blind, randomized, active-controlled, multicenter, phase IIb trial of patients with AIH without evidence of cirrhosis who were given budesonide (3 mg, three times daily or twice daily) or prednisone (40 mg/d, tapered to 10 mg/d); patients also received azathioprine (12 mg/kg/d). Treatment was followed by a 6-month, open-label phase during which all patients received budesonide in addition to azathioprine. The primary end point was complete biochemical remission, defined as normal serum levels of aspartate aminotransferase and alanine aminotransferase, without predefined steroid-specific side effects, at 6 months. Results The primary end point was achieved in 47/100 patients given budesonide (47.0%) and in 19/103 patients given prednisone (18.4%) (P <.001; 97.5% 1-side confidence interval [CI] = 16.2). At 6 months, complete biochemical remission occurred in 60% of the patients given budesonide versus 38.8% of those given prednisone (P = .001; CI: 7.7); 72.0% of those in the budesonide group did not develop steroid-specific side effects versus 46.6% in the prednisone group (P <.001; CI = 12.3). Among 87 patients who were initially given prednisone and then received budesonide after 6 months, steroid-specific side effects decreased from 44.8% to 26.4% at month 12 (P <.002). Conclusions Oral budesonide, in combination with azathioprine, induces and maintains remission in patients with noncirrhotic AIH, with a low rate of steroid-specific side effects.

Original languageEnglish
Pages (from-to)1198-1206
Number of pages9
JournalGastroenterology
Volume139
Issue number4
DOIs
Publication statusPublished - 2010

Fingerprint

Budesonide
Autoimmune Hepatitis
Prednisone
Azathioprine
Steroids
Confidence Intervals
Fibrosis
Liver Failure
Aspartate Aminotransferases
Alanine Transaminase
Liver Diseases
Adrenal Cortex Hormones
Chronic Disease
Therapeutics

ASJC Scopus subject areas

  • Gastroenterology
  • Medicine(all)

Cite this

Manns, M. P., Woynarowski, M., Kreisel, W., Lurie, Y., Rust, C., Zuckerman, E., ... Strassburg, C. P. (2010). Budesonide induces remission more effectively than prednisone in a controlled trial of patients with autoimmune hepatitis. Gastroenterology, 139(4), 1198-1206. https://doi.org/10.1053/j.gastro.2010.06.046

Budesonide induces remission more effectively than prednisone in a controlled trial of patients with autoimmune hepatitis. / Manns, Michael P.; Woynarowski, Marek; Kreisel, Wolfgang; Lurie, Yoav; Rust, Christian; Zuckerman, Elimelech; Bahr, Matthias J.; Gnther, Rainer; Hultcrantz, Rolf W.; Spengler, Ulrich; Lohse, Ansgar W.; Szalay, F.; Frkkil, Martti; Prls, Markus; Strassburg, Christian P.

In: Gastroenterology, Vol. 139, No. 4, 2010, p. 1198-1206.

Research output: Article

Manns, MP, Woynarowski, M, Kreisel, W, Lurie, Y, Rust, C, Zuckerman, E, Bahr, MJ, Gnther, R, Hultcrantz, RW, Spengler, U, Lohse, AW, Szalay, F, Frkkil, M, Prls, M & Strassburg, CP 2010, 'Budesonide induces remission more effectively than prednisone in a controlled trial of patients with autoimmune hepatitis', Gastroenterology, vol. 139, no. 4, pp. 1198-1206. https://doi.org/10.1053/j.gastro.2010.06.046
Manns, Michael P. ; Woynarowski, Marek ; Kreisel, Wolfgang ; Lurie, Yoav ; Rust, Christian ; Zuckerman, Elimelech ; Bahr, Matthias J. ; Gnther, Rainer ; Hultcrantz, Rolf W. ; Spengler, Ulrich ; Lohse, Ansgar W. ; Szalay, F. ; Frkkil, Martti ; Prls, Markus ; Strassburg, Christian P. / Budesonide induces remission more effectively than prednisone in a controlled trial of patients with autoimmune hepatitis. In: Gastroenterology. 2010 ; Vol. 139, No. 4. pp. 1198-1206.
@article{5b10fa5c16b4454bb578d981c28d26e1,
title = "Budesonide induces remission more effectively than prednisone in a controlled trial of patients with autoimmune hepatitis",
abstract = "Background & Aims Autoimmune hepatitis (AIH) is a chronic liver disease associated with cirrhosis and liver failure. Corticosteroid therapy induces long-term remission but has many side effects. We compared the effects of budesonide (a steroid that is rapidly metabolized, with low systemic exposure) and prednisone, both in combination with azathioprine. Methods We performed a 6-month, prospective, double-blind, randomized, active-controlled, multicenter, phase IIb trial of patients with AIH without evidence of cirrhosis who were given budesonide (3 mg, three times daily or twice daily) or prednisone (40 mg/d, tapered to 10 mg/d); patients also received azathioprine (12 mg/kg/d). Treatment was followed by a 6-month, open-label phase during which all patients received budesonide in addition to azathioprine. The primary end point was complete biochemical remission, defined as normal serum levels of aspartate aminotransferase and alanine aminotransferase, without predefined steroid-specific side effects, at 6 months. Results The primary end point was achieved in 47/100 patients given budesonide (47.0{\%}) and in 19/103 patients given prednisone (18.4{\%}) (P <.001; 97.5{\%} 1-side confidence interval [CI] = 16.2). At 6 months, complete biochemical remission occurred in 60{\%} of the patients given budesonide versus 38.8{\%} of those given prednisone (P = .001; CI: 7.7); 72.0{\%} of those in the budesonide group did not develop steroid-specific side effects versus 46.6{\%} in the prednisone group (P <.001; CI = 12.3). Among 87 patients who were initially given prednisone and then received budesonide after 6 months, steroid-specific side effects decreased from 44.8{\%} to 26.4{\%} at month 12 (P <.002). Conclusions Oral budesonide, in combination with azathioprine, induces and maintains remission in patients with noncirrhotic AIH, with a low rate of steroid-specific side effects.",
keywords = "Autoimmune Hepatitis, Azathioprine, Budesonide, Prednisone, Remission, Steroid Side Effects",
author = "Manns, {Michael P.} and Marek Woynarowski and Wolfgang Kreisel and Yoav Lurie and Christian Rust and Elimelech Zuckerman and Bahr, {Matthias J.} and Rainer Gnther and Hultcrantz, {Rolf W.} and Ulrich Spengler and Lohse, {Ansgar W.} and F. Szalay and Martti Frkkil and Markus Prls and Strassburg, {Christian P.}",
year = "2010",
doi = "10.1053/j.gastro.2010.06.046",
language = "English",
volume = "139",
pages = "1198--1206",
journal = "Gastroenterology",
issn = "0016-5085",
publisher = "W.B. Saunders Ltd",
number = "4",

}

TY - JOUR

T1 - Budesonide induces remission more effectively than prednisone in a controlled trial of patients with autoimmune hepatitis

AU - Manns, Michael P.

AU - Woynarowski, Marek

AU - Kreisel, Wolfgang

AU - Lurie, Yoav

AU - Rust, Christian

AU - Zuckerman, Elimelech

AU - Bahr, Matthias J.

AU - Gnther, Rainer

AU - Hultcrantz, Rolf W.

AU - Spengler, Ulrich

AU - Lohse, Ansgar W.

AU - Szalay, F.

AU - Frkkil, Martti

AU - Prls, Markus

AU - Strassburg, Christian P.

PY - 2010

Y1 - 2010

N2 - Background & Aims Autoimmune hepatitis (AIH) is a chronic liver disease associated with cirrhosis and liver failure. Corticosteroid therapy induces long-term remission but has many side effects. We compared the effects of budesonide (a steroid that is rapidly metabolized, with low systemic exposure) and prednisone, both in combination with azathioprine. Methods We performed a 6-month, prospective, double-blind, randomized, active-controlled, multicenter, phase IIb trial of patients with AIH without evidence of cirrhosis who were given budesonide (3 mg, three times daily or twice daily) or prednisone (40 mg/d, tapered to 10 mg/d); patients also received azathioprine (12 mg/kg/d). Treatment was followed by a 6-month, open-label phase during which all patients received budesonide in addition to azathioprine. The primary end point was complete biochemical remission, defined as normal serum levels of aspartate aminotransferase and alanine aminotransferase, without predefined steroid-specific side effects, at 6 months. Results The primary end point was achieved in 47/100 patients given budesonide (47.0%) and in 19/103 patients given prednisone (18.4%) (P <.001; 97.5% 1-side confidence interval [CI] = 16.2). At 6 months, complete biochemical remission occurred in 60% of the patients given budesonide versus 38.8% of those given prednisone (P = .001; CI: 7.7); 72.0% of those in the budesonide group did not develop steroid-specific side effects versus 46.6% in the prednisone group (P <.001; CI = 12.3). Among 87 patients who were initially given prednisone and then received budesonide after 6 months, steroid-specific side effects decreased from 44.8% to 26.4% at month 12 (P <.002). Conclusions Oral budesonide, in combination with azathioprine, induces and maintains remission in patients with noncirrhotic AIH, with a low rate of steroid-specific side effects.

AB - Background & Aims Autoimmune hepatitis (AIH) is a chronic liver disease associated with cirrhosis and liver failure. Corticosteroid therapy induces long-term remission but has many side effects. We compared the effects of budesonide (a steroid that is rapidly metabolized, with low systemic exposure) and prednisone, both in combination with azathioprine. Methods We performed a 6-month, prospective, double-blind, randomized, active-controlled, multicenter, phase IIb trial of patients with AIH without evidence of cirrhosis who were given budesonide (3 mg, three times daily or twice daily) or prednisone (40 mg/d, tapered to 10 mg/d); patients also received azathioprine (12 mg/kg/d). Treatment was followed by a 6-month, open-label phase during which all patients received budesonide in addition to azathioprine. The primary end point was complete biochemical remission, defined as normal serum levels of aspartate aminotransferase and alanine aminotransferase, without predefined steroid-specific side effects, at 6 months. Results The primary end point was achieved in 47/100 patients given budesonide (47.0%) and in 19/103 patients given prednisone (18.4%) (P <.001; 97.5% 1-side confidence interval [CI] = 16.2). At 6 months, complete biochemical remission occurred in 60% of the patients given budesonide versus 38.8% of those given prednisone (P = .001; CI: 7.7); 72.0% of those in the budesonide group did not develop steroid-specific side effects versus 46.6% in the prednisone group (P <.001; CI = 12.3). Among 87 patients who were initially given prednisone and then received budesonide after 6 months, steroid-specific side effects decreased from 44.8% to 26.4% at month 12 (P <.002). Conclusions Oral budesonide, in combination with azathioprine, induces and maintains remission in patients with noncirrhotic AIH, with a low rate of steroid-specific side effects.

KW - Autoimmune Hepatitis

KW - Azathioprine

KW - Budesonide

KW - Prednisone

KW - Remission

KW - Steroid Side Effects

UR - http://www.scopus.com/inward/record.url?scp=77957345684&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77957345684&partnerID=8YFLogxK

U2 - 10.1053/j.gastro.2010.06.046

DO - 10.1053/j.gastro.2010.06.046

M3 - Article

C2 - 20600032

AN - SCOPUS:77957345684

VL - 139

SP - 1198

EP - 1206

JO - Gastroenterology

JF - Gastroenterology

SN - 0016-5085

IS - 4

ER -