title: Maintenance treatment with azathioprine in ulcerative colitis: outcome and predictive factors after drug withdrawal.
abstract: OBJECTIVE
  Whether the duration of maintenance treatment with azathioprine (AZA) affects the outcome of ulcerative colitis (UC) is unclear. We investigated clinical outcomes and any predictive factors after withdrawal of AZA in UC.
  
  
  METHODS
  In this multicenter observational retrospective study, 127 Italian UC patients, who were in steroid-free remission at the time of withdrawal of AZA, were followed-up for a median of 55 months or until relapse. The frequency of clinical relapse or colectomy after AZA withdrawal was analyzed according to demographic, clinical, and endoscopic variables.
  
  
  RESULTS
  After drug withdrawal, a third of the patients relapsed within 12 months, half within 2 years and two-thirds within 5 years. After multivariable analysis, predictors of relapse after drug withdrawal were lack of sustained remission during AZA maintenance (hazard ratio, HR 2.350, confidence interval, CI 95% 1.434-3.852; P=0.001), extensive colitis (HR 1.793, CI 95% 1.064-3.023, P=0.028 vs. left-sided colitis; HR 2.024, CI 95% 1.103-3.717, P=0.023 vs. distal colitis), and treatment duration, with short treatments (3-6 months) more disadvantaged than >48-month treatments (HR 2.783, CI 95% 1.267-6.114, P=0.008). Concomitant aminosalicylates were the only predictors of sustained remission during AZA therapy (P=0.009). The overall colectomy rate was 10%. Predictors of colectomy were drug-related toxicity as the cause of AZA withdrawal (P=0.041), no post-AZA drug therapy (P=0.031), and treatment duration (P<0.0005).
  
  
  CONCLUSIONS
  Discontinuation of AZA while UC is in remission is associated with a high relapse rate. Disease extent, lack of sustained remission during AZA, and discontinuation due to toxicity could stratify relapse risk. Concomitant aminosalicylates were advantageous. Prospective randomized controlled trials are needed to confirm whether treatment duration is inversely associated with outcome.
authors.affiliation: Department of Clinical Sciences, Gastroenterology Unit, Luigi Sacco University Hospital, Milano, Italy. andreacassinotti@libero.it
authors.forename: Andrea
authors.initials: A
authors.lastname: Cassinotti
authors.forename: Giovanni C
authors.initials: GC
authors.lastname: Actis
authors.forename: Piergiorgio
authors.initials: P
authors.lastname: Duca
authors.forename: Alessandro
authors.initials: A
authors.lastname: Massari
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Colombo
authors.forename: Elisa
authors.initials: E
authors.lastname: Gai
authors.forename: Vito
authors.initials: V
authors.lastname: Annese
authors.forename: Giuseppe
authors.initials: G
authors.lastname: D'Albasio
authors.forename: Gianpiero
authors.initials: G
authors.lastname: Manes
authors.forename: Simon
authors.initials: S
authors.lastname: Travis
authors.forename: Gabriele Bianchi
authors.initials: GB
authors.lastname: Porro
authors.forename: Sandro
authors.initials: S
authors.lastname: Ardizzone
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D001379:Azathioprine / Q000627:therapeutic use*; D015331:Cohort Studies; D003093:Colitis, Ulcerative / Q000175:diagnosis / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D015994:Incidence; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011237:Predictive Value of Tests; D011336:Probability; D016016:Proportional Hazards Models; D012008:Recurrence; D012189:Retrospective Studies; D018570:Risk Assessment; D012720:Severity of Illness Index; D013375:Substance Withdrawal Syndrome / Q000175:diagnosis* / Q000453:epidemiology; D013997:Time Factors; D016896:Treatment Outcome; D028761:Withholding Treatment; D055815:Young Adult
chemical_list: D007166:Immunosuppressive Agents; D001379:Azathioprine