title: Budesonide induces remission more effectively than prednisone in a controlled trial of patients with autoimmune hepatitis.
abstract: OBJECTIVE
  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 (1-2 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.
authors.affiliation: Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany. manns.michael@mh-hannover.de
authors.forename: Michael P
authors.initials: MP
authors.lastname: Manns
authors.forename: Marek
authors.initials: M
authors.lastname: Woynarowski
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Kreisel
authors.forename: Yoav
authors.initials: Y
authors.lastname: Lurie
authors.forename: Christian
authors.initials: C
authors.lastname: Rust
authors.forename: Elimelech
authors.initials: E
authors.lastname: Zuckerman
authors.forename: Matthias J
authors.initials: MJ
authors.lastname: Bahr
authors.forename: Rainer
authors.initials: R
authors.lastname: Günther
authors.forename: Rolf W
authors.initials: RW
authors.lastname: Hultcrantz
authors.forename: Ulrich
authors.initials: U
authors.lastname: Spengler
authors.forename: Ansgar W
authors.initials: AW
authors.lastname: Lohse
authors.forename: Ferenc
authors.initials: F
authors.lastname: Szalay
authors.forename: Martti
authors.initials: M
authors.lastname: Färkkilä
authors.forename: Markus
authors.initials: M
authors.lastname: Pröls
authors.forename: Christian P
authors.initials: CP
authors.lastname: Strassburg
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D019819:Budesonide / Q000009:adverse effects / Q000627:therapeutic use*; D002648:Child; D004311:Double-Blind Method; D005260:Female; D015803:HLA-DR3 Antigen / Q000032:analysis; D019693:Hepatitis, Autoimmune / Q000188:drug therapy* / Q000276:immunology; D006801:Humans; D008297:Male; D008875:Middle Aged; D011241:Prednisone / Q000009:adverse effects / Q000627:therapeutic use*; D011446:Prospective Studies
chemical_list: D015803:HLA-DR3 Antigen; D019819:Budesonide; D011241:Prednisone