Oral budesonide and ursodeoxycholic acid for treatment of primary biliary cirrhosis: results of a prospective double-blind trial.
OBJECTIVE
Ursodeoxycholic acid (UDCA) is used for treatment of primary biliary cirrhosis. Previous studies showed that, compared with UDCA monotherapy, bile salts plus prednisolone had no further effect on laboratory data but improved liver histology. Thirty percent of these patients had prednisolone-related side effects. Budesonide is a glucocorticoid with a high receptor affinity and a high first-pass metabolism. In this study we investigated whether budesonide and UDCA are superior to UDCA monotherapy.


METHODS
A 2-year prospective, controlled double-blind trial was performed. Twenty patients (mainly with early-stage disease) were treated with UDCA at a dose of 10-15 mg/kg daily in addition to 3 mg budesonide 3 times daily (group A), and 19 patients (1 dropped out for personal reasons) were treated with UDCA plus placebo (group B). Liver biopsy specimens were taken before, after 12 months, and at the end of study. Glucose tolerance tests, serum cortisol levels, and adrenocorticotropin-stimulated cortisol secretion were assessed at regular intervals. Bone mass density was measured by dual-energy photon absorptiometry.


RESULTS
Compared with pretreatment values, liver enzyme and immunoglobulin M and G levels decreased significantly in both groups. Improvement in group A was significantly more pronounced (P < 0.05) than in group B. Titers of antimitochondrial antibodies did not change. In group A, the point score of liver histology improved by 30.3%; in group B, it deteriorated by 3.5% (P < 0.001). Changes in bone mineral density after 2 years were -1.747% in group A and -0.983% in group B (P = 0.43). Budesonide had little influence on the hypothalamic-pituitary-adrenal axis. One patient in group A had budesonide-related side effects; in 3 patients in group B, complications of liver disease developed.


CONCLUSIONS
Combination therapy with UDCA and budesonide is superior to UDCA and placebo.
Leuschner
M
M
Medical Clinic II, University Hospital Frankfurt/Main, Germany.
Maier
K P
KP
Schlichting
J
J
Strahl
S
S
Herrmann
G
G
Dahm
H H
HH
Ackermann
H
H
Happ
J
J
Leuschner
U
U
D000284:Administration, Oral; D000287:Administration, Topical; D000893:Anti-Inflammatory Agents / Q000009:adverse effects / Q000627:therapeutic use*; D019819:Budesonide / Q000009:adverse effects / Q000627:therapeutic use*; D002756:Cholagogues and Choleretics / Q000009:adverse effects / Q000627:therapeutic use*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D005938:Glucocorticoids; D006801:Humans; D007074:Immunoglobulin G / Q000378:metabolism; D007075:Immunoglobulin M / Q000378:metabolism; D008099:Liver / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D008105:Liver Cirrhosis, Biliary / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D016896:Treatment Outcome; D014580:Ursodeoxycholic Acid / Q000009:adverse effects / Q000627:therapeutic use*
D000893:Anti-Inflammatory Agents; D002756:Cholagogues and Choleretics; D005938:Glucocorticoids; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D019819:Budesonide; D014580:Ursodeoxycholic Acid