W1187 Outcome Following Infliximab Therapy in Pediatric Patients with Ulcerative Colitis: Results from a Multicenter Study

Abstract

Background: Children with severe ulcerative colitis resistant to corticosteroids either need to undergo surgery or be treated with more intensive immunosuppression (e.g. cyclosporine, tacrolimus, infliximab). The short and long term efficacy of such therapies is not well described in children. Methods: From 1994 to 2008, 52 children (26M; mean age 13y, range 4-21 y) with steroid-refractory colitis were treated with tacrolimus at our institution. Medical record reviewwas performed on these patients. Data extracted allowed the calculation of the Pediatric Ulcerative Colitis Activity Index (PUCAI). In addition, other measures of disease activity, adverse events, and long-term outcomes were assessed. Statistical analysis of outcomes was performed using SAS statistical software. Results: Out of 52 patients, 46 were treated with tacrolimus with the intent to transition to maintenance medical therapy, while 6 were treated to allow corticosteroid weaning prior to elective colectomy. The median dose of tacrolimus utilized was 0.2 mg/kg/day (range 0.1-0.5 mg/kg/day) in two divided doses; the median trough level during induction therapy was 11 ng/ml. The median length of stay after the institution of tacrolimus was 10 days (range 3-37 days). The mean PUCAI score was 66.8 (±14.3 SD) prior to the initiation of tacrolimus therapy, and 21.9 (±14.8 SD) at time of hospital discharge. Of the 46 patients that were treated with the aim of postponing surgery, 43/46 (94%) were discharged without surgery. Patients were maintained on tacrolimus for 3 to 6 months (median 114 days), and transitioned to maintenance therapy (6MP, AZA, or infliximab). The probability of colectomy in this patient cohort was 7% at 1 month, 14% at 3 months, 30% at 12 months, and 57% at 25 months. No colectomies were performed in patients followed for longer than 25 months (longest follow-up 13 years). The most common adverse events noted in the first three months included tremor (32%), hypertension (21%), infections (9%), creatinine >1.5 x baseline (9%), and hyperglycemia (8%). These adverse effects resolved with weaning of steroids or transition to maintenance therapy. Conclusion: Tacrolimus is effective induction therapy in corticosteroid refractory colitis, and is generally well tolerated. However, many patients will develop exacerbations of colitis upon transition to maintenance therapies. The long term colectomy rate in this challenging population remains approximately 60% over time.