title: The efficacy of oral tacrolimus in patients with moderate/severe ulcerative colitis not receiving concomitant corticosteroid therapy.
abstract: OBJECTIVE
  The calcineurin inhibitor tacrolimus has been shown to be safe and effective as salvage therapy for steroid-refractory ulcerative colitis (UC). Since differences in the onset of action between various agents are thought to influence the achievement and maintenance of disease remission, top-down or accelerated step-up therapy with tacrolimus may be useful. However, the efficacy of tacrolimus in moderate to severe UC patients not receiving concomitant steroids remains unknown.
  
  
  METHODS
  Ten patients (11 attacks) with active, moderate to severe UC were treated with oral tacrolimus at a dose of 0.1 mg/kg body weight daily. The dosages were adapted to maintain trough whole-blood levels of 10 to 15 ng/mL to induce remission and 5 to 10 ng/mL to maintain remission. Lichtiger scores, the incidence of adverse effects (serum creatinine and glucose) and long-term outcomes were assessed.
  
  
  RESULTS
  At four weeks after the initiation of tacrolimus therapy, clinical remissions were observed for eight attacks (72.7%) and clinical responses were demonstrated for three attacks. At 12 weeks after the initiation of tacrolimus treatment, clinical remissions were achieved for nine attacks (90%). After a mean follow-up of 10.4 months, clinical remissions were maintained for eight of 11 attacks. During the tacrolimus treatment, the serum creatinine and glucose levels were not significantly elevated.
  
  
  CONCLUSIONS
  Oral tacrolimus is a safe and effective therapy for the treatment of moderate to severe UC in patients not receiving concomitant treatment with systemic steroids. Although further studies are required to establish the efficacy and safety of oral tacrolimus therapy in patients with UC, oral tacrolimus may represent a top-down or accelerated step-up treatment option for patients with moderate to severe UC.
authors.affiliation: Second Department of Internal Medicine, Osaka Medical College, Japan. ureuretakuwan@yahoo.co.jp
authors.forename: Takuya
authors.initials: T
authors.lastname: Inoue
authors.forename: Mitsuyuki
authors.initials: M
authors.lastname: Murano
authors.forename: Ken
authors.initials: K
authors.lastname: Narabayashi
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Okada
authors.forename: Sadaharu
authors.initials: S
authors.lastname: Nouda
authors.forename: Kumi
authors.initials: K
authors.lastname: Ishida
authors.forename: Ken
authors.initials: K
authors.lastname: Kawakami
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Abe
authors.forename: Toshihisa
authors.initials: T
authors.lastname: Takeuchi
authors.forename: Satoshi
authors.initials: S
authors.lastname: Tokioka
authors.forename: Eiji
authors.initials: E
authors.lastname: Umegaki
authors.forename: Kazuhide
authors.initials: K
authors.lastname: Higuchi
mesh_terms: D000284:Administration, Oral; D000305:Adrenal Cortex Hormones; D000328:Adult; D015331:Cohort Studies; D003093:Colitis, Ulcerative / Q000175:diagnosis* / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D016099:Endoscopy, Gastrointestinal; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D007413:Intestinal Mucosa / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D061214:Patient Safety; D012189:Retrospective Studies; D012720:Severity of Illness Index; D016559:Tacrolimus / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000305:Adrenal Cortex Hormones; D007166:Immunosuppressive Agents; D016559:Tacrolimus