title: Low-dose maintenance steroid treatment could reduce the relapse rate in patients with type 1 autoimmune pancreatitis: a long-term Japanese multicenter analysis of 510 patients.
abstract: BACKGROUND
  The effect of maintenance steroid treatment (MST) in reducing the risk of relapse in patients with autoimmune pancreatitis (AIP) remains under debate. The aim of this study was to validate the effect of MST on AIP administered in accordance with the 2010 Japanese consensus guidelines.
  
  
  METHODS
  The clinical data of patients with (n = 510) from 22 high-volume centers in Japan were studied. The primary endpoints were the relapse rates (RRs) in patients administered MST versus those not administered MST. The secondary endpoints were the optimal dose and duration of MST in terms of steroid toxicity and the predictors of relapse.
  
  
  RESULTS
  The RRs were 10.0% within 1 year, 25.8% within 3 years and 35.1% within 5 years. The RR in the steroid therapy group reached a plateau at 42.7% at 7 years. In terms of the optimal dosage, the overall RR in the MST 5 mg/day group was 26.1%, which was significantly lower than that in the group which had discontinued steroid therapy (45.2%; p = 0.023) or was receiving MST at 2.5 mg/day (43.4%, p = 0.001). The RRs in the group receiving MST at ≥5 mg/day versus the patient group receiving MST at <5 mg/day were 10.6 vs. 10.3% within 1 year, 23.5 vs. 32.9% within 3 years and 32.2 vs. 41.3% within 5 years, respectively (log-rank, p = 0.028). The best cutoff value of the total steroid dose for serious steroid toxicity was 6405 mg, with a moderate accuracy of 0.717 determined using the area under the curve. Presence of diffuse pancreatic swelling [odds ratio OR) 1.745; p = 0.008) and MST at >5 mg/day were identified as predictors of relapse (OR 0.483; p = 0.001).
  
  
  CONCLUSIONS
  The RR could continue to increase for 7 years even under MST. Based on our analysis of the side effects of steroid therapy, MST at 5 mg/day for 2 (total 4625 mg) to 3 (total 6425 mg) years might be a rational and safe therapeutic strategy in terms of keeping the RR to <30% while avoiding potential steroid toxicity.
authors.affiliation: Department of Endoscopy, Yokohama City University Hospital, Yokohama, Japan.
authors.forename: Kensuke
authors.initials: K
authors.lastname: Kubota
authors.affiliation: Department of Internal Medicine, Tokyo Komagome Metropolitan Hospital, Tokyo, Japan. kamisawa@cick.jp.
authors.forename: Terumi
authors.initials: T
authors.lastname: Kamisawa
authors.affiliation: Department of Gastroenterology and Hepatology, Kansai Medical University, Hirakata, Japan.
authors.forename: Kazuichi
authors.initials: K
authors.lastname: Okazaki
authors.affiliation: Center for Health, Safety and Environmental Management, Shinshu University, Matsumoto, Japan.
authors.forename: Shigeyuki
authors.initials: S
authors.lastname: Kawa
authors.affiliation: Department of Gastroenterology, Graduate School of Medicine, Tokyo University, Tokyo, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Hirano
authors.affiliation: Department of Endoscopy, Nagoya University Hospital, Nagoya, Japan.
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Hirooka
authors.affiliation: Department of Gastroenterology and Hepatology, Kansai Medical University, Hirakata, Japan.
authors.forename: Kazushige
authors.initials: K
authors.lastname: Uchida
authors.affiliation: Department of Gastroenterology, Graduate School of Medicine, Kobe University, Kobe, Japan.
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Shiomi
authors.affiliation: Department of Community-Based Medical Education, Graduate School of Medicine, Nagoya City University, Nagoya, Japan.
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Ohara
authors.affiliation: Gastroenterology, Tokyo Women's Medical University, Tokyo, Japan.
authors.forename: Kyoko
authors.initials: K
authors.lastname: Shimizu
authors.affiliation: Department of Gastroenterology, Graduate School of Medicine, Shinshu University, Matsumoto, Japan.
authors.forename: Norikazu
authors.initials: N
authors.lastname: Arakura
authors.affiliation: Department of Gastroenterology, Graduate School of Medicine, Tohoku University, Sendai, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Kanno
authors.affiliation: Department of Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Junichi
authors.initials: J
authors.lastname: Sakagami
authors.affiliation: Department of Gastroenterology, Tokyo Medical University, Tokyo, Japan.
authors.forename: Takao
authors.initials: T
authors.lastname: Itoi
authors.affiliation: Department of Medicine and Bioregulatory Science, Graduate School of Medicine, Kyushu University, Fukuoka, Japan.
authors.forename: Tetsuhide
authors.initials: T
authors.lastname: Ito
authors.affiliation: Department of Gastroenterology, Chikushi Hospital, Fukuoka University, Fukuoka, Japan.
authors.forename: Toshiharu
authors.initials: T
authors.lastname: Ueki
authors.affiliation: Department of Gastroenterology, Yachiyo Hospital, Tokyo Women's Medical University, Tokyo, Japan.
authors.forename: Takayoshi
authors.initials: T
authors.lastname: Nishino
authors.affiliation: Department of Gastroenterology, Second Teaching Hospital, Fujita Health University, Toyoake, Japan.
authors.forename: Kazuo
authors.initials: K
authors.lastname: Inui
authors.affiliation: Department of Gastroenterology, Aichi Cancer Center, Nagoya, Japan.
authors.forename: Nobumasa
authors.initials: N
authors.lastname: Mizuno
authors.affiliation: Department of Gastroenterology, School of Medicine, Showa University, Tokyo, Japan.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Yoshida
authors.affiliation: Department of Surgery, School of Medicine, Kyorin University, Tokyo, Japan.
authors.forename: Masanori
authors.initials: M
authors.lastname: Sugiyama
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University, Tokyo, Japan.
authors.forename: Eisuke
authors.initials: E
authors.lastname: Iwasaki
authors.affiliation: Department of Gastroenterology, Aizu Medical Center, Fukushima Medical University, Fukushima, Japan.
authors.forename: Atshishi
authors.initials: A
authors.lastname: Irisawa
authors.affiliation: Department of Gastroenterology, Graduate School of Medicine, Tohoku University, Sendai, Japan.
authors.forename: Toru
authors.initials: T
authors.lastname: Shimosegawa
authors.affiliation: Division of Hepato-Biliary-Pancreatic Surgery, Department of Surgery, Kinki University Faculty of Medicine, Osaka, Japan.
authors.forename: Yoshifumi
authors.initials: Y
authors.lastname: Takeyama
authors.affiliation: Gastroenterology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Chiba
mesh_terms: D000368:Aged; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage* / Q000009:adverse effects; D001327:Autoimmune Diseases / Q000188:drug therapy*; D001379:Azathioprine / Q000627:therapeutic use; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007564:Japan; D060046:Maintenance Chemotherapy; D008297:Male; D008875:Middle Aged; D050500:Pancreatitis, Chronic / Q000188:drug therapy* / Q000276:immunology; D011239:Prednisolone / Q000008:administration & dosage* / Q000009:adverse effects; D012008:Recurrence; D012307:Risk Factors; D055502:Secondary Prevention; D013997:Time Factors
chemical_list: D000893:Anti-Inflammatory Agents; D007166:Immunosuppressive Agents; D011239:Prednisolone; D001379:Azathioprine
keywords: Autoimmune pancreatitis; Maintenance steroid treatment; Relapse rate; Steroid toxicity