Talwalkar JA et al. (2007) Tacrolimus for the treatment of primary sclerosing cholangitis. Liver Int 27: 451–453

In light of the promising results of a pilot study, Talwalkar et al. investigated whether or not tacrolimus is indeed safe and efficacious in patients with primary sclerosing cholangitis (PSC).

Sixteen PSC patients with serum alkaline phosphatase levels at least 1.5 times the upper limit of normal were enrolled in this open-label phase II trial. Participants received tacrolimus 0.05 mg/kg twice daily (target whole-blood concentration 3–7 ng/ml) for 1 year. The tacrolimus dose was adjusted at least once in nine of the participants based on their whole-blood tacrolimus concentration, serum creatinine level or drug-related adverse events reported.

Drug-related adverse events were observed in 13 participants. There were eight participants who failed to complete the treatment: five withdrew owing to drug-related adverse effects, two failed to take the drug after enrolment and one died in an accident. A statistically and clinically significant reduction in the median serum alkaline phosphatase level (903 vs 483, P = 0.0001) was observed in the eight patients who completed treatment, and there was a statistically but not clinically significant reduction in the median aspartate aminotransferase level (88 vs 78, P = 0.002). No statistically or clinically significant reductions in total bilirubin or albumin levels were observed.

Although these findings confirm that tacrolimus improves the serum alkaline phosphatase level in patients with PSC, the authors suggest that the clinical benefit of tacrolimus is limited due to poor patient tolerance.