title: Adrenomedullin Therapy in Patients with Refractory Ulcerative Colitis: A Case Series.
abstract: OBJECTIVE
  Adrenomedullin (AM) is a multifunctional biologically active peptide that has an ameliorative effect against inflammatory bowel disease in several experimental models. We reported the first case where AM infusion dramatically improved symptoms and colonoscopy findings in patients with refractory ulcerative colitis (UC). To confirm the reproducibility of the efficacy and safety of AM infusion, this pilot study evaluated the clinical feasibility of intravenous administration of AM in patients with refractory UC.
  
  
  METHODS
  Seven patients with active refractory UC participated and received intravenous infusion of AM (1.5 pmol/kg/min) for 8 h daily for 14 days, and their Disease Activity Index (DAI) were evaluated before and 2 and 12 weeks after beginning AM administration.
  
  
  RESULTS
  DAI were improved in all patients after AM administration. Within 2 weeks, marked declines in DAI (≥ 3 points and ≥ 30%) were observed in six patients (85.7%), while a more modest decline was observed in one patient (14.3%). Overall mean DAI improved from 9.3 ± 0.6 at baseline to 4.6 ± 0.8 at 2 weeks, and then to 1.2 ± 0.5 at 12 weeks. Endoscopic examination revealed substantial amelioration of ulcers, with mucosal healing and scarring. Four patients remained in clinical remission 12 months after AM treatment. AM administration produced significant increases in plasma AM concentrations (approximately 2.5-fold) that had a mild effect on blood pressure and heart rate, but with no serious adverse effects.
  
  
  CONCLUSIONS
  AM is a potentially useful agent that acts via a novel mechanism to safely induce mucosal healing and clinical remission in patients with refractory UC.
authors.affiliation: Circulatory and Body Fluid Regulation, Faculty of Medicine, University of Miyazaki, 5200 Kihara, Kiyotake, Miyazaki, 889-1692, Japan. shinya_ashizuka@med.miyazaki-u.ac.jp.
authors.forename: Shinya
authors.initials: S
authors.lastname: Ashizuka
authors.affiliation: Circulatory and Body Fluid Regulation, Faculty of Medicine, University of Miyazaki, 5200 Kihara, Kiyotake, Miyazaki, 889-1692, Japan. inacchi@med.miyazaki-u.ac.jp.
authors.forename: Haruhiko
authors.initials: H
authors.lastname: Inatsu
authors.affiliation: Circulatory and Body Fluid Regulation, Faculty of Medicine, University of Miyazaki, 5200 Kihara, Kiyotake, Miyazaki, 889-1692, Japan. toshihiro_kita@med.miyazaki-u.ac.jp.
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Kita
authors.affiliation: Circulatory and Body Fluid Regulation, Faculty of Medicine, University of Miyazaki, 5200 Kihara, Kiyotake, Miyazaki, 889-1692, Japan. kazuokit@med.miyazaki-u.ac.jp.
authors.forename: Kazuo
authors.initials: K
authors.lastname: Kitamura
mesh_terms: D053607:Adrenomedullin / Q000627:therapeutic use*; D000328:Adult; D000368:Aged; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use; D001379:Azathioprine / Q000627:therapeutic use; D003093:Colitis, Ulcerative / Q000188:drug therapy* / Q000473:pathology; D004359:Drug Therapy, Combination; D005260:Female; D005938:Glucocorticoids / Q000627:therapeutic use; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D008297:Male; D019804:Mesalamine / Q000627:therapeutic use; D008875:Middle Aged; D010865:Pilot Projects; D011239:Prednisolone / Q000627:therapeutic use; D011446:Prospective Studies; D016559:Tacrolimus / Q000627:therapeutic use; D016896:Treatment Outcome; D014665:Vasodilator Agents / Q000627:therapeutic use*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D005938:Glucocorticoids; D007166:Immunosuppressive Agents; D014665:Vasodilator Agents; D053607:Adrenomedullin; D019804:Mesalamine; D011239:Prednisolone; D001379:Azathioprine; D016559:Tacrolimus
keywords: Adrenomedullin; Biologically active peptide; Clinical pilot study; Mucosal healing; Ulcerative colitis