title: Azathioprine dose escalation in inflammatory bowel disease.
abstract: BACKGROUND
  Forty per cent of patients with inflammatory bowel disease fail to respond to standard dose azathioprine (2 mg/kg/day).
  
  
  OBJECTIVE
  To evaluate the efficacy and safety of increasing the azathioprine dose according to a fixed schedule and guided by clinical response and adverse effects.
  
  
  METHODS
  We reviewed the records of all patients with inflammatory bowel disease treated by a single clinician over 6 years, unresponsive to at least 3 months treatment with standard dose azathioprine, and whose dose was subsequently increased.
  
  
  RESULTS
  Forty patients (27 male; 24 Crohn's, 16 ulcerative colitis) with chronic active disease or recurrent flares despite standard dose azathioprine for a median 8 months (range 3-114) increased their dose from a median 2.02 (1.61-3.19) mg/kg/day to 2.72 (2.37-3.99) mg/kg/day in one to four increments of 0.5 mg/kg/day, and were followed over a median 6 (0.5-54) months. Eleven of the 40 patients (seven Crohn's, four ulcerative colitis) responded or had reduced frequency of flare-ups at the end of follow-up, while 17 of the 40 patients had no benefit. Response was more likely for maximum doses < or =2.5 mg/kg/day (six of 11 patients) than for doses >2.5 mg/kg/day (five of 29 patients) (P = 0.042). Twelve patients (11 of whom received maximum doses >2.5 mg/kg/day) were unable to maintain an increased azathioprine dose because of leukopenia in eight, nausea in three, and raised liver enzymes in one (all transient and reversible).
  
  
  CONCLUSIONS
  Increasing the azathioprine dose up to 2.5 mg/kg/day appears beneficial in patients who have not responded to 2 mg/kg/day. Further increase above 2.5 mg/kg/day is less likely to be efficacious, and is associated with a substantial risk of adverse reactions.
authors.affiliation: St Mark's Hospital, London, UK.
authors.forename: C K
authors.initials: CK
authors.lastname: Rayner
authors.forename: A L
authors.initials: AL
authors.lastname: Hart
authors.forename: C M M
authors.initials: CM
authors.lastname: Hayward
authors.forename: A V
authors.initials: AV
authors.lastname: Emmanuel
authors.forename: M A
authors.initials: MA
authors.lastname: Kamm
mesh_terms: D000328:Adult; D001379:Azathioprine / Q000008:administration & dosage* / Q000009:adverse effects; D003093:Colitis, Ulcerative / Q000188:drug therapy*; D003424:Crohn Disease / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D004341:Drug Evaluation; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D016896:Treatment Outcome
chemical_list: D007166:Immunosuppressive Agents; D001379:Azathioprine