Budesonide or prednisone in combination with ursodeoxycholic acid in primary sclerosing cholangitis: a randomized double-blind pilot study. Belgian-Dutch PSC Study Group.
OBJECTIVE
PSC has characteristics of an (auto)immune-mediated disease: however, few studies have evaluated corticosteroid therapy for this disorder.


METHODS
We performed an 8-wk double-blind randomized pilot study to assess the effects of additional treatment with 9 mg budesonide (n = 6) versus 3 mg budesonide (n = 6) versus 10 mg prednisone (n = 6) in patients who had been treated with UDCA (mean dose, 12 mg/kg/day) for at least 5 months without achieving biochemical remission. Pruritus and fatigue were evaluated using visual analog scales. Serum liver biochemistry was measured every 4 wk. At entry and at the end of the trial, adrenocorticotrophic hormone (ACTH) and dehydroepiandrosterone (DHEA) were measured to assess effects on the pituitary-adrenal axis. Duodenal bile was collected for assessment of biliary corticosteroid activity.


RESULTS
Pruritus decreased significantly more in the prednisone group compared to both the 3-mg and the 9-mg budesonide groups (p < 0.05). Alkaline phosphatase (mean: -23.4%; p = 0.03) and IgG (mean: -16.2%; p = 0.04) decreased in the prednisone group, whereas bilirubin, gamma-glutamyl transferase, aspartate aminotransferase, and alanine aminotransferase did not change significantly. No significant clinical or liver biochemical changes were observed in the 3-mg and 9-mg budesonide groups. Significantly larger drops in serum ACTH were found in the 10-mg prednisone group (-40.7%; p = 0.04) and 9-mg budesonide group (-36.6%; p = 0.02) compared to the 3-mg budesonide group (+ 19.0%). No significant differences in percentage change in baseline values for DHEA between the three treatment arms were found. Mononuclear cell proliferation assays did not demonstrate corticosteroid activity in bile. Autoimmune hepatitis was observed in one case (9 mg budesonide) when corticosteroids were tapered off.


CONCLUSIONS
The results of this pilot study suggest only minor beneficial short-term effects of prednisone but not budesonide on symptoms and serum liver tests in UDCA-treated PSC patients.
van Hoogstraten
H J
HJ
Department of Hepatogastroenterology, University Hospital Rotterdam, The Netherlands.
Vleggaar
F P
FP
Boland
G J
GJ
van Steenbergen
W
W
Griffioen
P
P
Hop
W C
WC
van Hattum
J
J
van Berge Henegouwen
G P
GP
Schalm
S W
SW
van Buuren
H R
HR
D000305:Adrenal Cortex Hormones / Q000378:metabolism; D000324:Adrenocorticotropic Hormone / Q000097:blood; D000328:Adult; D000469:Alkaline Phosphatase / Q000097:blood; D000893:Anti-Inflammatory Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001646:Bile / Q000378:metabolism; D019819:Budesonide / Q000009:adverse effects / Q000627:therapeutic use*; D002756:Cholagogues and Choleretics / Q000009:adverse effects / Q000627:therapeutic use*; D015209:Cholangitis, Sclerosing / Q000150:complications / Q000188:drug therapy*; D004311:Double-Blind Method; D005221:Fatigue / Q000209:etiology; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D011241:Prednisone / Q000009:adverse effects / Q000627:therapeutic use*; D011537:Pruritus / Q000209:etiology; D014580:Ursodeoxycholic Acid / Q000009:adverse effects / Q000627:therapeutic use*
D000305:Adrenal Cortex Hormones; D000893:Anti-Inflammatory Agents; D002756:Cholagogues and Choleretics; D007074:Immunoglobulin G; D019819:Budesonide; D014580:Ursodeoxycholic Acid; D000324:Adrenocorticotropic Hormone; D000469:Alkaline Phosphatase; D011241:Prednisone