Combination therapy with oral tacrolimus (FK506) and azathioprine or 6-mercaptopurine for treatment-refractory Crohn's disease perianal fistulae

Our aim was to report the clinical experience with combination treatment us ing tacrolimus and either azathioprine (AZA) or 6-mercaptopurine (6MP) in p atients with Crohn's disease (CD) perianal fistulae. The medical records of all patients with Crohn's disease perianal fistulae seen at the Mayo Clini c from 1996-1998 who were treated with tacrolimus were reviewed. Clinical r esponse was classified as: complete response, partial response, and nonresp onse. Eleven patients were treated with oral tacrolimus for a mean duration of 22 weeks. The initial oral dose of tacrolimus ranged from 0.15 to 0.31 mg/kg/day. Azathioprine or 6MP was continued in combination with tacrolimus in seven patients and initiated simultaneously with tacrolimus in four pat ients. ALI patients improved clinically, seven had a complete response, and four had a partial response. The mean time to initial improvement was 2.4 weeks, and the mean time to complete response was 12.2 weeks. The most freq uent adverse events were nausea, paresthesias, nephrotoxicity, and tremor. Patients with nephrotoxicity had a significantly higher mean initial tacrol imus dose (0.31 mg/kg/day) compared with patients who did not have nephroto xicity (0.25 mg/kg/day) (p = 0.035); however, there was not a statistically significant association between the starting dose or mean blood level and clinical response. Combination therapy with oral tacrolimus and AZA or 6MP may be effective treatment for CD perianal fistulae. Higher initial tacroli mus doses increase the risk of nephrotoxicity without improving clinical re sponse.