INTRODUCTION: Oral tacrolimus can induce remission in children with severe colitis (Gastroenterology 1997; 112:A941). We now report the results of our four year experience with oral tacrolimus.
METHODS: Sixteen hospitalized patients (4 Crohn's, 10 UC, 2 indeterminate colitis; 11 male; age range 6-20 years) with severe colitis unresponsive to at least 1 week of intravenous steroids were enrolled. Inclusion criteria included steroid-unresponsive colitis with more than 4 bloody stools/day, pre-transfusion hematocrit <25% or serum albumin <3.0 g/dL. Oral tacrolimus (0.1 mg/kg/dose every 12 hours) was given in addition to steroids and supportive therapy. Tacrolimus dosage was adjusted to give a whole blood trough level of 10-15 ng/ml. When remission was achieved, levels were adjusted downward to 5-10 ng/ml. The tacrolimus was given for 90 days. Six-mercaptopurine was begun 30-45 days after the start of tacrolimus for maintenance.
RESULTS: Therapeutic drug levels were readily achieved in all 16 patients. One patient elected to withdraw from the study after 48 hours. Four patients did not respond and underwent colectomy within 14 days. Eleven of fifteen patients (73%) responded to oral tacrolimus therapy within 14 days. In these 11 patients, the mean Lichtiger colitis score declined from 13.7 to 3.8 points, the mean stool frequency decreased from 8.1 to 2.4 stools/day, and hospital discharge on full oral feedings occurred between 7-38 days after the initiation of tacrolimus. Adverse effects included headache (n=2), hand tremor (n=3), myalgias (n=1), hypertension (n=2), hyperglycemia (n=2), and postoperative seizure (n=1). Four patients who initially responded underwent colectomy at 1,1,8, and 11 months after their tacrolimus treatment. The remaining 7 patients are controlled on medical therapy with followup of 4,9,13,15,18,32, and 41 months post-tacrolimus.
CONCLUSION: While tacrolimus is an effective induction therapy for severe ulcerative or Crohn's colitis, less than 50% of patients treated will successfully achieve a long-term remission.