title: Prolonged thioguanine therapy is well tolerated and safe in the treatment of ulcerative colitis.
abstract: BACKGROUND
  Thioguanine has been used for the treatment of inflammatory bowel disease, in particular for patients who failed conventional thiopurine therapy. To date, thioguanine has been infrequently studied in ulcerative colitis.
  
  
  OBJECTIVE
  To evaluate the tolerability, safety and efficacy of thioguanine in the treatment of ulcerative colitis.
  
  
  METHODS
  A database analysis was performed on inflammatory bowel disease patients who had failed conventional thiopurine therapy and were treated with thioguanine. Rates and reasons for treatment failure were assessed. Laboratory values, abdominal ultrasonography, liver biopsy and endoscopic remission rates were evaluated.
  
  
  RESULTS
  Forty-six patients were included and median treatment duration was 22 months (range 0.3-72.0). Nine patients failed thioguanine therapy: six due to adverse events, three due to therapy resistance. Concomitant treatment with aminosalicylates protected against thioguanine failure (hazard ratio (HR) 0.11, 95% CI 0.03-0.48). When performed, ultrasonography (n = 21) revealed no suspected therapy-related pathology in all but one patient, in whom hepatomegaly was observed. Liver histology (n = 12) predominantly revealed no abnormalities (n = 4) or non-specific regeneration (n = 4); none showed nodular regenerative hyperplasia. At follow-up, 40% of colonoscopies revealed endoscopic remission as compared with 10% at baseline (P = 0.180).
  
  
  CONCLUSIONS
  Long-term use of thioguanine appears to be well tolerated and relatively safe in ulcerative colitis patients who failed conventional thiopurine therapy.
authors.affiliation: Department of Gastroenterology and Hepatology, VU University Medical Centre, Amsterdam, The Netherlands. d.vanasseldonk@vumc.nl
authors.forename: Dirk P
authors.initials: DP
authors.lastname: van Asseldonk
authors.forename: Bindia
authors.initials: B
authors.lastname: Jharap
authors.forename: Dirk J
authors.initials: DJ
authors.lastname: Kuik
authors.forename: Nanne K H
authors.initials: NK
authors.lastname: de Boer
authors.forename: Barend D
authors.initials: BD
authors.lastname: Westerveld
authors.forename: Maurice G V M
authors.initials: MG
authors.lastname: Russel
authors.forename: Frank J G M
authors.initials: FJ
authors.lastname: Kubben
authors.forename: Ad A
authors.initials: AA
authors.lastname: van Bodegraven
authors.forename: Chris J
authors.initials: CJ
authors.lastname: Mulder
mesh_terms: D000328:Adult; D000368:Aged; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage; D003093:Colitis, Ulcerative / Q000175:diagnosis / Q000188:drug therapy*; D016208:Databases, Factual; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D005765:Gastrointestinal Agents / Q000008:administration & dosage* / Q000009:adverse effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D009426:Netherlands; D016017:Odds Ratio; D013866:Thioguanine / Q000008:administration & dosage* / Q000009:adverse effects; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D005765:Gastrointestinal Agents; D013866:Thioguanine