Local application of tacrolimus in distal colitis: feasible and safe

Background: Tacrolimus is a potent immunomodulator that is effective in the systemic treatment of inflammatory bowel diseases (IBD). However, potential toxicity and systemic (side) effects after oral intake limit its use. We investigated the local applicability and Safety of tacrolimus for distal colitis. Methods: Patients; with refractory left-sided colitis or proctitis were treated for 4 weeks with a daily tacrolimus 2-4 mg enema or 2 mg suppository. Safety of local tacrolimus treatment was assessed by measurement of whole blood tacrolimus trough levels by monitoring liver and kidney function and blood glucose levels. Efficacy of treatment was assessed by comparing the disease activity index (DAI) in ulcerative colitis (UC) patients and endoscopic and histologic appearances before and after 4 weeks of treatment. Results: Nineteen patients with left-sided colitis (n = 7) or proctitis (n 12) were treated. Two patients with left-sided colitis had Crohn's disease (Cl)), the other 17 patients had UC. None of the patients developed side effects. Blood trough levels of tacrolimus were too low to induce systemic immune Suppression. Thirteen of 19 patients (3/5 left-sided UC, 0/2 left-sided CD, and 10/12 proctitis) showed clinical improvement of disease activity after 4 weeks of local tacrolimus treatment. Moreover, a significant improvement of histological appearance was observed in the suppository-treated group. Conclusions: This study demonstrates that local colonic application of tacrolimus 2-4 mg daily in patients with refractory distal colitis is Feasible, probably safe, and potentially efficacious, and therefore opens the need for a further, randomized trial.