Oral Tacrolimus in Steroid Refractory and Dependent Pediatric Ulcerative Colitis-A Systematic Review and Meta-Analysis.

Abstract

There are limited treatment options for children with steroid-refractory or dependent ulcerative colitis (UC). A few observational studies suggest efficacy of oral tacrolimus. We performed a systematic review and meta-analysis to assess the efficacy of tacrolimus in pediatric UC. PubMed and Scopus were searched for publications related to the use of oral tacrolimus in pediatric UC. Data regarding the clinical response and colectomy-free survival were extracted from studies that met the selection criteria. The search strategy yielded 492 articles of which 7 studies were included in the final review. They included 166 children (111 steroid-refractory, 52 steroid-dependent, 3 no steroids). Majority of cases (150/166 [90%]) were naïve to biologics. An initial response to tacrolimus therapy was seen in 84% (95% CI: 73%-93%) (n = 7 studies). No difference was observed between children with high (>10 ng/mL) or low tacrolimus levels (127/150 [85%] vs 12/16 [75%], P = 0.3). No difference in initial response between the children who were steroid refractory or dependent (92/111 [83%] vs 46/52 [88%], P = 0.36). The response in the biologic-exposed group (n = 10) was 70%. At 1-year follow-up, 15.2% (95% CI: 7%-21%) (n = 2 studies, 85 patients) had a sustained response on only tacrolimus. The pooled frequency of 1-year colectomy-free survival in children treated with initial oral tacrolimus was 64% (95% CI: 53%-75%). Twelve (7.2%) patients required cessation of therapy because of side effects. Tacrolimus has a high initial response in biologic naïve UC children. It can be effectively used as a bridge to other therapies with a 1-year colectomy-free survival of 64%.