No beneficial effects of transdermal nicotine in patients with primary sclerosing cholangitis: results of a randomized double-blind placebo-controlled cross-over study.
OBJECTIVE
Smoking is associated with a decreased risk of primary sclerosing cholangitis. We aimed to explore the therapeutic efficacy of and tolerance for transdermal nicotine treatment in this disease.


METHODS
Twelve patients (11 males; 37 +/- 6 years; six with ulcerative colitis) who did not achieve complete biochemical remission on ursodeoxycholic acid (14 mg/ kg/day) were treated in a randomized cross-over trial with transdermal nicotine (15 mg/day) or a placebo, each for 8 weeks (4-week washout period between treatments).


RESULTS
One patient developed de novo ulcerative colitis and two did not complete the entire protocol because of intercurrent bacterial cholangitis. Baseline values [mean (range)] were: bilirubin, 1.3 (0.5-2.6); alkaline phosphatase (APh), 2.5 (1.4-4.7); gamma-glutamyl transpeptidase (gammaGT), 7.7 (0.7-38); aspartate aminotransferase (AST), 1.9 (0.5-3.2); alanine aminotransferase (ALT), 2.4 (0.4-7.3); and bile salts, 10.9 (2.1 -39) times the upper limit of normal. No significant effect on pruritus or fatigue was noted during either period, but a small increase in bodyweight was observed during placebo treatment. No significant differences were observed between the two treatment modalities after 8 weeks in bilirubin (nicotine versus placebo, +13% versus -6% change from baseline), APh (-3% versus -17%), gammaGT (-11% versus -13%), AST (+2% versus -10%), ALT (-1% versus -11%) or bile salts (+36% versus -3%).


CONCLUSIONS
Transdermal nicotine does not seem to have a clear short-term beneficial effect in primary sclerosing cholangitis treated with ursodeoxycholic acid.
Department of Hepatology and Gastroenterology, University Hospital, Rotterdam, The Netherlands.
F P
FP
Vleggaar
H R
HR
van Buuren
G P
GP
van Berge Henegouwen
W C
WC
Hop
K J
KJ
van Erpecum
D000279:Administration, Cutaneous; D000328:Adult; D015415:Biomarkers / Q000097:blood; D015209:Cholangitis, Sclerosing / Q000097:blood / Q000188:drug therapy*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D009538:Nicotine / Q000008:administration & dosage / Q000627:therapeutic use*; D018722:Nicotinic Agonists / Q000008:administration & dosage / Q000627:therapeutic use*; D014580:Ursodeoxycholic Acid / Q000627:therapeutic use
D015415:Biomarkers; D018722:Nicotinic Agonists; D009538:Nicotine; D014580:Ursodeoxycholic Acid