Clinical Trials Study
Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Feb 14, 2015; 21(6): 1880-1886
Published online Feb 14, 2015. doi: 10.3748/wjg.v21.i6.1880
Effects of oral tacrolimus as a rapid induction therapy in ulcerative colitis
Ken Kawakami, Takuya Inoue, Mitsuyuki Murano, Ken Narabayashi, Sadaharu Nouda, Kumi Ishida, Yosuke Abe, Koji Nogami, Nobuyuki Hida, Hirokazu Yamagami, Kenji Watanabe, Eiji Umegaki, Shiro Nakamura, Tetsuo Arakawa, Kazuhide Higuchi
Ken Kawakami, Takuya Inoue, Mitsuyuki Murano, Ken Narabayashi, Sadaharu Nouda, Kumi Ishida, Yosuke Abe, Eiji Umegaki, Kazuhide Higuchi, Second Department of Internal Medicine, Osaka Medical College, Osaka 569-8686, Japan
Koji Nogami, Nobuyuki Hida, Shiro Nakamura, Division of Lower Gastroenterology, Department of Internal Medicine, Hyogo College of Medicine, Hyogo Prefecture 663-8131, Japan
Hirokazu Yamagami, Kenji Watanabe, Tetsuo Arakawa, Department of Gastroenterology, Osaka City University Graduate School of Medicine, Osaka 569-8686, Japan
Author contributions: Kawakami K and Inoue T performed data compilation, analysis, statistical analysis and manuscript preparation; Murono M, Narabayashi K, Nouda S, Ishida K, Abe Y, Nogami K, Hida N, Yamagami H and Watanabe K have performed the tacrolimus treatment; Umegaki E assisted in the analysis and interpretation of data; Higuchi K, Nakamura S and Arakawa T revised this manuscript.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Ken Kawakami, MD, Second Department of Internal Medicine, Osaka Medical College, 2-7 Daigakumachi, Takatsuki city, Osaka 569-8686, Japan. in2090@poh.osaka-med.ac.jp
Telephone: +81-72-6831221 Fax: +81-72-6846532
Received: June 16, 2014
Peer-review started: June 17, 2014
First decision: July 21, 2014
Revised: August 13, 2014
Accepted: September 18, 2014
Article in press: September 19, 2014
Published online: February 14, 2015
Processing time: 239 Days and 18.9 Hours
Abstract

AIM: To determine the efficacy and safety of rapid induction therapy with oral tacrolimus without a meal in steroid-refractory ulcerative colitis (UC) patients.

METHODS: This was a prospective, multicenter, observational study. Between May 2010 and August 2012, 49 steroid-refractory UC patients (55 flare-ups) were consecutively enrolled. All patients were treated with oral tacrolimus without a meal at an initial dose of 0.1 mg/kg per day. The dose was adjusted to maintain trough whole-blood levels of 10-15 ng/mL for the first 2 wk. Induction of remission at 2 and 4 wk after tacrolimus treatment initiation was evaluated using Lichtiger’s clinical activity index (CAI).

RESULTS: The mean CAI was 12.6 ± 3.6 at onset. Within the first 7 d, 93.5% of patients maintained high trough levels (10-15 ng/mL). The CAI significantly decreased beginning 2 d after treatment initiation. At 2 wk, 73.1% of patients experienced clinical responses. After tacrolimus initiation, 31.4% and 75.6% of patients achieved clinical remission at 2 and 4 wk, respectively. Treatment was well tolerated.

CONCLUSION: Rapid induction therapy with oral tacrolimus shortened the time to achievement of appropriate trough levels and demonstrated a high remission rate 28 d after treatment initiation. Rapid induction therapy with oral tacrolimus appears to be a useful therapy for the treatment of refractory UC.

Keywords: Ulcerative colitis; Tacrolimus; Rapid induction therapy; Steroid-refractory ulcerative colitis; Inflammatory bowel disease

Core tip: A prospective, multicenter, observation study was conducted to determine the efficacy and safety of rapid induction therapy with oral tacrolimus without meal in patients with steroid-refractory ulcerative colitis. Rapid induction therapy could achieve the appropriate trough level (10-15 ng/mL) within the first 7 d and revealed a high remission rate 28 d after the initiation of the treatment. Treatment was well tolerated. Rapid induction therapy with oral tacrolimus appears to be a useful therapy for the treatment of refractory ulcerative colitis.