title: Azathioprine is essential following cyclosporine for patients with steroid-refractory ulcerative colitis.
abstract: OBJECTIVE
  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).
  
  
  CONCLUSIONS
  Maintenance therapy with azathioprine might improve the long-term efficacy of continuously infused cyclosporine for severe steroid-refractory ulcerative colitis patients.
authors.affiliation: 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.
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Miyake
authors.affiliation: 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.
authors.forename: Takafumi
authors.initials: T
authors.lastname: Ando
authors.affiliation: 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.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Ishiguro
authors.affiliation: 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.
authors.forename: Osamu
authors.initials: O
authors.lastname: Maeda
authors.affiliation: 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.
authors.forename: Osamu
authors.initials: O
authors.lastname: Watanabe
authors.affiliation: 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.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Hirayama
authors.affiliation: 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.
authors.forename: Keiko
authors.initials: K
authors.lastname: Maeda
authors.affiliation: 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.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Morise
authors.affiliation: 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.
authors.forename: Masanobu
authors.initials: M
authors.lastname: Matsushita
authors.affiliation: 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.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Furukawa
authors.affiliation: 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.
authors.forename: Kohei
authors.initials: K
authors.lastname: Funasaka
authors.affiliation: 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.
authors.forename: Masanao
authors.initials: M
authors.lastname: Nakamura
authors.affiliation: 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.
authors.forename: Ryoji
authors.initials: R
authors.lastname: Miyahara
authors.affiliation: 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.
authors.forename: Naoki
authors.initials: N
authors.lastname: Ohmiya
authors.affiliation: 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.
authors.forename: Hidemi
authors.initials: H
authors.lastname: Goto
mesh_terms: D000293:Adolescent; D000305:Adrenal Cortex Hormones / Q000008:administration & dosage* / Q000009:adverse effects; D000328:Adult; D001379:Azathioprine / Q000008:administration & dosage* / Q000009:adverse effects; D002648:Child; D003093:Colitis, Ulcerative / Q000175:diagnosis / Q000188:drug therapy*; D016572:Cyclosporine / Q000008:administration & dosage* / Q000009:adverse effects; D004334:Drug Administration Schedule; D004351:Drug Resistance; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000009:adverse effects; D007262:Infusions, Intravenous; D007564:Japan; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000305:Adrenal Cortex Hormones; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D001379:Azathioprine
keywords: Azathioprine; Cyclosporine; Long-term prognosis; Maintenance therapy; Ulcerative colitis