P355 Efficacy and safety of oral tacrolimus for the treatment of severe steroid-resistant ulcerative colitis

Abstract

Background: Ulcerative colitis (UC) that occurs in childhood is usually an extensive colitis or pancolitis and is most often associated with severe steroid-refractory flares. Tacrolimus is a second-line drug therapy indicated in patients with severe flare that is unresponsive to steroid therapy. Objective: to describe our experience of the efficacy and safety of oral tacrolimus treatment in children with steroid-resistant severe ulcerative colitis. Methods: We conducted a retrospective study that included all patients under 18 years suffering from serious flares of ulcerative colitis treated with oral tacrolimus during the period between January 1998 and October 2011. All patients received an oral dose of 0.12mg/kg/day. The drug dosage was adjusted to achieve a plasma trough level of tacrolimus between 5 and 10 ng/mL. For statistical analysis and preparation of the survival curves we used the SPSS version 17.0 for Windows program. A p value <0.01 was considered as significant. Results: A total of 10 patients, 7 women were included. Seven patiens were in their first attack of the disease. The mean age was 9.4±4.9 years-old, and the time course of the disease of 1.3 months (IQR, 1 to 5.7m). The initial clinical response was achieved in 6 patients. All nonresponders required colectomy within one month after initiation of treatment. In the subgroup that responded initially, 2 of 6 patients required colectomy, one at 10 months after starting treatment and the other one at 6 years and 4 months after the immunomodulatory therapy was stopped. Plasma trough levels of tacrolimus were 4 13 ng/ml. The median duration of treatment in the responder group was 4.7 months (IQ, 3.7 to 6) versus 0.23 months in the nonresponders (IQ 0.13 to 0.8m), p = 0.01. Tacrolimus was well tolerated in all cases. Conclusions: Tacrolimus is useful in inducing remission in patients with acute, severe steroid-resistant flares of ulcerative colitis. It can change the course of the disease, and it can prevent or delay surgery allowing to prepare the patient and his family for a probable surgery.