Intest Res.  2019 Oct;17(4):476-485. 10.5217/ir.2019.00027.

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

• Yanagi T
• Ushijima K
• Koga H
• Tomomasa T
• Tajiri H
• Kunisaki R
• Isihige T
• Yamada H
• Arai K
• Yoden A
• Aomatsu T
• Nagata S
• Uchida K
• Ohtsuka Y
• Shimizu T

• KMID: 2465813
• DOI: http://doi.org/10.5217/ir.2019.00027

Abstract

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.

Keyword

Immunologic factors; Biological factors; Remission induction; Colectomy

MeSH Terms

Adult
Asian Continental Ancestry Group
Biological Factors
Child*
Colectomy
Colitis
Colitis, Ulcerative*
Female
Humans
Immunologic Factors
Japan*
Prednisolone
Remission Induction
Retrospective Studies
Tacrolimus*
Ulcer*
Biological Factors
Immunologic Factors
Prednisolone
Tacrolimus

Figure

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  Fig. 1. Patient flow of short- and long-term effects in this study.

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  Fig. 2. Short- and long-term effects of tacrolimus therapy. Short-term effects, defined as remission or response within 2 weeks of tacrolimus therapy, were achieved in 85.1% of patients (remission: 47.8%; response: 37.3%). As a long-term effect, the event-free survival rate was 11.9% (14% of those who achieved short-term remission or response).

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  Fig. 3. Event-free survival rate between remission and response groups classified according to short-term effect. We found no significant difference between the 2 groups (remission and response) for the event-free survival rate 1 year after tacrolimus administration, based on Kaplan-Meier analysis (log-rank test, P=0.33).

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  Fig. 4. Event-free survival rate in the steroid-dependent and steroid-refractory groups. We found no significant difference between steroid-dependent and steroid-refractory groups for the event-free survival rate 1 year after tacrolimus administration, based on Kaplan-Meier analysis (log-rank test, P=0.52).

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