Budesonide induces remission more effectively than prednisone in a controlled trial of patients with autoimmune hepatitis.
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.
Manns
Michael P
MP
Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany. manns.michael@mh-hannover.de
Woynarowski
Marek
M
Kreisel
Wolfgang
W
Lurie
Yoav
Y
Rust
Christian
C
Zuckerman
Elimelech
E
Bahr
Matthias J
MJ
Günther
Rainer
R
Hultcrantz
Rolf W
RW
Spengler
Ulrich
U
Lohse
Ansgar W
AW
Szalay
Ferenc
F
Färkkilä
Martti
M
Pröls
Markus
M
Strassburg
Christian P
CP
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
D015803:HLA-DR3 Antigen; D019819:Budesonide; D011241:Prednisone