title: Tacrolimus salvage in anti-tumor necrosis factor antibody treatment-refractory Crohn's disease.
abstract: BACKGROUND
  Several small retrospective studies have reported encouraging response rates in patients with Crohn's disease (CD) treated with tacrolimus.
  
  
  METHODS
  We conducted a retrospective study of the use of oral tacrolimus for severe CD refractory to anti-tumor necrosis factor agents. Response was defined as a clinician's assessment of improvement after at least 7 days of treatment of one or more of the following: bowel movement frequency, fistula output, rectal bleeding, abdominal pain, extraintestinal manifestations, or well-being. Remission required all of the following: <3 stools per day, no bleeding, abdominal pain or extraintestinal manifestations, and increased well-being.
  
  
  RESULTS
  Twenty-four eligible patients were treated with tacrolimus for a median of 4 months. Approximately 37% were steroid dependent or steroid refractory. Response and steroid-free remission rates were 67% and 21%, respectively, and lasted for a median of 4 months. Approximately 42% of patients were able to stop steroids and 54% of patients ultimately required surgery within a median of 10 months after starting tacrolimus. Patients with mean tacrolimus trough levels of 10 to 15 ng/mL had the highest rates of response (86%) and remission (57%). Surgery seemed to be postponed in this group compared with others. An adverse event occurred in 75% of patients. Eight of these events (33%) required dose reduction and 6 (25%) led to treatment discontinuation. There were no irreversible side effects or deaths attributable to tacrolimus over a median follow-up of 56 months.
  
  
  CONCLUSIONS
  Oral tacrolimus seems to be safe and effective in some patients with severe CD refractory to anti-tumor necrosis factor therapy, particularly at a mean trough level of 10 to 15 ng/mL.
authors.affiliation: Division of Gastroenterology and Hepatology, University of Colorado Denver, Aurora, Colorado 80045, USA. mark.gerich@ucdenver.edu
authors.forename: Mark E
authors.initials: ME
authors.lastname: Gerich
authors.forename: Darrell S
authors.initials: DS
authors.lastname: Pardi
authors.forename: David H
authors.initials: DH
authors.lastname: Bruining
authors.forename: Patricia P
authors.initials: PP
authors.lastname: Kammer
authors.forename: Brenda D
authors.initials: BD
authors.lastname: Becker
authors.forename: William T
authors.initials: WT
authors.lastname: Tremaine
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D003424:Crohn Disease / Q000188:drug therapy*; D004351:Drug Resistance / Q000187:drug effects*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D000069285:Infliximab; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012189:Retrospective Studies; D016879:Salvage Therapy; D016559:Tacrolimus / Q000627:therapeutic use*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*; D055815:Young Adult
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D000911:Antibodies, Monoclonal; D007166:Immunosuppressive Agents; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab; D016559:Tacrolimus