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Summary

Background

Emerging data suggest that oral antibiotics may have therapeutic effects in primary sclerosing cholangitis (PSC), but published studies are limited.

Aims

To investigate the safety and efficacy of oral vancomycin and metronidazole in patients with PSC.

Methods

Thirty-five patients with PSC were randomised in a double-blind manner into four groups: vancomycin 125 mg or 250 mg four times/day, or metronidazole 250 mg or 500 mg three times/day for 12 weeks. The primary endpoint was decrease in alkaline phosphatase (ALK) at 12 weeks. Secondary end points included serum bilirubin and Mayo PSC risk score; pruritus; and adverse effects (AEs). Nonparametric tests were used for analysis.

Results

The primary endpoint was reached in the low-dose (−43% change in ALK,= 0.03) and high-dose (−40%, = 0.02) vancomycin groups, with two patients in the former experiencing ALK normalisation. Bilirubin decreased significantly in the low-dose metronidazole group (−20%, = 0.03) and trended towards significance in the low-dose vancomycin group (−33%, = 0.06). Mayo PSC risk score decreased significantly in the low-dose vancomycin (−0.55, = 0.02) and low-dose metronidazole group (−0.16, = 0.03). Pruritus decreased significantly in the high-dose metronidazole group (−3.4, = 0.03). AEs led to medication discontinuation in six patients, four of whom were receiving metronidazole.

Conclusions

Both vancomycin and metronidazole demonstrated efficacy; however, only patients in the vancomycin groups reached the primary endpoint, and with less adverse effects. Larger, longer-term studies are needed to further examine the safety and efficacy of antibiotics as a potential treatment for patients with primary sclerosing cholangitis (clinicaltrials.gov NCT01085760).