Retrospective Study
Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jan 7, 2015; 21(1): 254-261
Published online Jan 7, 2015. doi: 10.3748/wjg.v21.i1.254
Azathioprine is essential following cyclosporine for patients with steroid-refractory ulcerative colitis
Nobuyuki Miyake, Takafumi Ando, Kazuhiro Ishiguro, Osamu Maeda, Osamu Watanabe, Yutaka Hirayama, Keiko Maeda, Kazuhiro Morise, Masanobu Matsushita, Kazuhiro Furukawa, Kohei Funasaka, Masanao Nakamura, Ryoji Miyahara, Naoki Ohmiya, Hidemi Goto
Nobuyuki Miyake, Takafumi Ando, Kazuhiro Ishiguro, Osamu Maeda, Osamu Watanabe, Yutaka Hirayama, Keiko Maeda, Kazuhiro Morise, Masanobu Matsushita, Kazuhiro Furukawa, Kohei Funasaka, Masanao Nakamura, Ryoji Miyahara, Hidemi Goto, Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya City, Aichi 466-8550, Japan
Naoki Ohmiya, Department of Gastroenterology, Fujita Health University School of Medicine, Toyoake, Aichi 470-1192, Japan
Author contributions: Miyake N, Ando T, Ishiguro K, Maeda O, Watanabe O designed research; Hirayama Y, Maeda K, Morise K, Matsushita M, Furukawa K, Funasaka K, Nakamura M, Miyahara R, Ohmiya N collected data; Miyake N and Ando T wrote the paper; Goto H provided the critical review of the 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: Takafumi Ando, MD, PhD, Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya City, Aichi 466-8550, Japan. takafumiando-gi@umin.ac.jp
Telephone: +81-52-7442144 Fax: +81-52-7442175
Received: March 11, 2014
Peer-review started: March 11, 2014
First decision: April 2, 2014
Revised: April 28, 2014
Accepted: July 22, 2014
Article in press: July 22, 2014
Published online: January 7, 2015
Processing time: 301 Days and 17.8 Hours
Abstract

AIM: To evaluate long-term prognosis following cyclosporine treatment by examining the rate of surgery avoidance among cyclosporine responders.

METHODS: We retrospectively reviewed clinical records for 29 patients diagnosed with severe steroid-refractory ulcerative colitis in our hospital from August 1997 to August 2008 and treated with cyclosporine by continuous intravenous infusion. All patients were treated with intravenous corticosteroids for more than 5 d prior to cyclosporine therapy. Administration was continued for up to 21 d under serum monitoring to maintain cyclosporine levels between 400 and 600 ng/mL. Clinical activity was assessed before and after cyclosporine therapy using the clinical activity index score, with a reduction of ≥ 5 considered to indicate a response. Among responders, we defined cases not requiring surgery for more than 5 years as exhibiting long-term efficacy of cyclosporine. Factors considered to be possibly predictive of long-term efficacy of cyclosporine were sex, age, disease duration, clinical activity index score, C-reactive protein level, hemoglobin level, disease extent, endoscopic findings, and clinical course.

RESULTS: Cyclosporine was not discontinued due to side effects in any patient. Nineteen (65.5%) of 29 patients were considered responders. A statistically significant (P = 0.004) inverse association was observed between an endoscopic finding of “mucosal bleeding” and responsive cases. Fifteen (9 males, 6 females) of these 19 patients were followed for 5 years or more, of whom 9 (60%) exhibited long-term efficacy of cyclosporine. Of the 10 non-responders, 9 (90%) underwent surgery within 6 mo of cyclosporine therapy. None of the following factors had a significant impact on the long-term efficacy of cyclosporine: sex, age, duration of disease, clinical activity index score, C-reactive protein level, hemoglobin level, extent of disease, endoscopic findings, or clinical course. In contrast, a significant association was observed for maintenance therapy with azathioprine after cyclosporine therapy (P = 0.0014).

CONCLUSION: Maintenance therapy with azathioprine might improve the long-term efficacy of continuously infused cyclosporine for severe steroid-refractory ulcerative colitis patients.

Keywords: Ulcerative colitis; Cyclosporine; Maintenance therapy; Azathioprine; Long-term prognosis

Core tip: Cyclosporine is effective in avoiding emergency surgery in patients with severe steroid-refractory ulcerative colitis. However, few studies have evaluated long-term outcomes of cyclosporine therapy in Asia. This paper provides important information regarding the maintenance of steroid-free remission following cyclosporine therapy. Maintenance therapy with azathioprine improves the long-term efficacy of continuously infused cyclosporine in patients with severe steroid-refractory ulcerative colitis.