title: Oral tacrolimus for the treatment of refractory inflammatory bowel disease in the biologic era.
abstract: BACKGROUND
  Patients with inflammatory bowel disease who are refractory to standard therapies frequently require surgery. The long-term efficacy of tacrolimus in patients who fail standard immunosuppressive and antitumor necrosis factor α therapy is unknown.
  
  
  METHODS
  Thirty-five patients (11 Crohn's disease and 24 ulcerative colitis) with medication-resistant disease were treated with oral tacrolimus and reviewed retrospectively. Patients were commenced on tacrolimus 0.1 mg/kg/day, with a trough level targeted between 8 and 12 ng/mL. Clinical response or remission at 30 days, 90 days, and 1 year was assessed. The overall risk of requiring surgery and predictive factors were also assessed.
  
  
  RESULTS
  All patients had failed a thiopurine, 5 (14%) had also failed methotrexate, while 90% had a primary or secondary nonresponse, or an incomplete response, to an antitumor necrosis factor α agent. The proportions that achieved a clinical response at 30 days, 90 days, and 1 year was 65.7%, 60%, and 31.4%, respectively, whereas the corresponding proportions in remission were 40%, 37.1%, and 22.9%. The cumulative risk of requiring surgery was 40.4% at 1 year and 59.3% at 2 years with a median time to surgery of 22 months (range, 0.5-84 months). Patients who were steroid refractory, or dependent, before starting tacrolimus were more likely to have surgery (P = 0.006), whereas patients who were able to achieve or maintain a clinical response with tacrolimus by 90 days were less likely (P = 0.004).
  
  
  CONCLUSIONS
  Tacrolimus is able to induce a clinical response in a third and remission in a fifth of medically refractory patients with inflammatory bowel disease at 1 year. A 90-day therapeutic trial is worthwhile in difficult to treat patients.
authors.affiliation: Centre for Inflammatory Bowel Diseases, Fremantle Hospital, Fremantle, Australia. lenathin@gmail.com
authors.forename: Lena W Y
authors.initials: LW
authors.lastname: Thin
authors.forename: Kevin
authors.initials: K
authors.lastname: Murray
authors.forename: Ian C
authors.initials: IC
authors.lastname: Lawrance
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D001688:Biological Products / Q000627:therapeutic use*; D003093:Colitis, Ulcerative / Q000188:drug therapy* / Q000401:mortality; D003424:Crohn Disease / Q000188:drug therapy* / Q000401:mortality; D004351:Drug Resistance / Q000187:drug effects*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D008297:Male; D011379:Prognosis; D012074:Remission Induction; D012189:Retrospective Studies; D016879:Salvage Therapy; D015996:Survival Rate; D016559:Tacrolimus / Q000627:therapeutic use*; D055815:Young Adult
chemical_list: D001688:Biological Products; D007166:Immunosuppressive Agents; D016559:Tacrolimus