Tacrolimus for ulcerative colitis in children: a multicenter survey in Japan

BACKGROUND/AIMS: Tacrolimus is effective for refractory ulcerative colitis in adults, while data for children is sparse. We aimed to evaluate the effectiveness and safety of tacrolimus for induction and maintenance therapy in Japanese children with ulcerative colitis.METHODS: We retrospectively reviewed the multicenter survey data of 67 patients with ulcerative colitis aged < 17 years treated with tacrolimus between 2000 and 2012. Patients’ characteristics, disease activity, Pediatric Ulcerative Colitis Activity Index (PUCAI) score, initial oral tacrolimus dose, short-term (2-week) and long-term (1-year) outcomes, steroid-sparing effects, and adverse events were evaluated. Clinical remission was defined as a PUCAI score < 10; treatment response was defined as a PUCAI score reduction of ≥ 20 points compared with baseline.RESULTS: Patients included 35 boys and 32 girls (median [interquartile range] at admission: 13 [11–15] years). Thirty-nine patients were steroid-dependent and 26 were steroidrefractory; 20 had severe colitis and 43 had moderate colitis. The initial tacrolimus dose was 0.09 mg/kg/day (range, 0.05–0.12 mg/kg/day). The short-term clinical remission rate was 47.8%, and the clinical response rate was 37.3%. The mean prednisolone dose was reduced from 19.2 mg/day at tacrolimus initiation to 5.7 mg/day at week 8 (P< 0.001). The adverse event rate was 53.7%; 6 patients required discontinuation of tacrolimus therapy.CONCLUSIONS: Tacrolimus was a safe and effective second-line induction therapy for steroid-dependent and steroid-refractory ulcerative colitis in Japanese children.

The relationship between the concentration of dextran sodium sulfate and the degree of induced experimental colitis in weanling rats.

BACKGROUND: Although a dextran sodium sulfate (DSS)-induced colitis is commonly used as an ulcerative colitis (UC) model in adult rodents, there are no studies using this model in young animals. We examined differences in the severity of DSS-induced colitis as a function of the concentration of DSS administered and sought to establish a DSS-induced colitis model in young rats. METHODS: We administrated different concentrations of DSS solution (2%, 3%, and 4%) to 4-week-old weanling rats and compared their clinical findings, colonic histologic findings, mucosal leukotriene B4 (LTB4) production, and mucosal blood flow with control weanling rats and 8-week-old adult rats given 4% DSS for induced colitis. RESULTS: Clinical symptoms, such as diarrhea and rectal bleeding, histologic findings, and disturbance of mucosal microcirculation in weanling rats given 4% DSS were significantly more severe than those in adult rats given the same treatment. Three of 10 rats given 2% DSS had no bloody stool and 2 of 10 rats given 4% DSS died during the experimental periods. Clinical symptoms, hemoglobin levels, histologic damage scores, mucosal LTB4 production, and mucosal blood flow became more severely deranged as the concentration of DSS increased from 2% to 4%. CONCLUSION: These findings suggest that we can adjust disease severity in UC model for young children by giving different concentrations of DSS to weanling rats.