title: Routine use of thiopurines in maintaining remission in pediatric Crohn's disease.
abstract: OBJECTIVE
  To evaluate the effectiveness of thiopurines in maintaining steroid-free remission in routine clinical practice.
  
  
  METHODS
  The multi-center Pediatric Inflammatory Bowel Disease Network (PIBDNet) cohort study prospectively collected data on thiopurine naïve patients initiating mercaptopurine (6MP) or azathioprine. Patients with a diagnosis of Crohn's disease (CD) were included in our study upon entering remission as determined by physician global assessment (PGA) within 365 d of initiation of thiopurines. The primary outcome of the study was maintenance of steroid-free remission (SFR) at each follow up visit. Patients were considered treatment failures if there had been a change in PGA from remission to mild, moderate or severe disease; disease relapse between visits; need for rescue therapy (biologic therapy, methotrexate, steroids); thiopurine discontinuation, hospitalization or surgical intervention. A secondary outcome defined treatment failure as a change from remission to moderate or severe (not mild) in addition to the previously defined criteria.
  
  
  RESULTS
  Sixty-five of 182 patients in the PIBDNet registry met criteria for inclusion in this study. Forty-five of 65 (69%) of included patients achieved remission within 180 d of thiopurine initiation. For the primary outcome, 47% and 23% of patients remained in SFR at 6 and 12 mo. The mean thiopurine dose at initiation for the 65 included patients was 0.89 ± 0.31 mg/kg per day. Metabolite levels were obtained in 48% (31/65) of the included patients with a mean 6TG level of 258 pmole/8 × 10(8) RBC ± 147. For the secondary outcome, 65% and 42% of patients remained in SFR at 6 and 12 mo.
  
  
  CONCLUSIONS
  Thiopurines were less effective in maintaining remission for pediatric CD in this "real world" cohort than has been previously described. Variation in thiopurine dosing and metabolite measurement was found among practitioners.
authors.affiliation: Brendan M Boyle, Wallace V Crandall, Nationwide Children's Hospital, Columbus, OH 43205, United States.
authors.forename: Brendan M
authors.initials: BM
authors.lastname: Boyle
authors.affiliation: Brendan M Boyle, Wallace V Crandall, Nationwide Children's Hospital, Columbus, OH 43205, United States.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Kappelman
authors.affiliation: Brendan M Boyle, Wallace V Crandall, Nationwide Children's Hospital, Columbus, OH 43205, United States.
authors.forename: Richard B
authors.initials: RB
authors.lastname: Colletti
authors.affiliation: Brendan M Boyle, Wallace V Crandall, Nationwide Children's Hospital, Columbus, OH 43205, United States.
authors.forename: Robert N
authors.initials: RN
authors.lastname: Baldassano
authors.affiliation: Brendan M Boyle, Wallace V Crandall, Nationwide Children's Hospital, Columbus, OH 43205, United States.
authors.forename: David E
authors.initials: DE
authors.lastname: Milov
authors.affiliation: Brendan M Boyle, Wallace V Crandall, Nationwide Children's Hospital, Columbus, OH 43205, United States.
authors.forename: Wallace V
authors.initials: WV
authors.lastname: Crandall
mesh_terms: D000293:Adolescent; D000367:Age Factors; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000097:blood / Q000627:therapeutic use*; D001379:Azathioprine / Q000008:administration & dosage / Q000097:blood / Q000627:therapeutic use*; D002648:Child; D003424:Crohn Disease / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy*; D016903:Drug Monitoring; D005260:Female; D005765:Gastrointestinal Agents / Q000008:administration & dosage / Q000097:blood / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D015122:Mercaptopurine / Q000008:administration & dosage / Q000097:blood / Q000627:therapeutic use*; D011446:Prospective Studies; D016032:Randomized Controlled Trials as Topic; D012008:Recurrence; D012042:Registries; D012074:Remission Induction; D012720:Severity of Illness Index; D013256:Steroids / Q000627:therapeutic use; D013997:Time Factors; D016896:Treatment Outcome; D014481:United States
chemical_list: D000893:Anti-Inflammatory Agents; D005765:Gastrointestinal Agents; D013256:Steroids; D015122:Mercaptopurine; D001379:Azathioprine
keywords: Crohn’s disease; Mercaptopurine; Pediatric; Remission; Thiopurines
references.citation: Inflamm Bowel Dis. 2008 Jul;14(7):949-54
references.pmid: 18306311
references.citation: Cochrane Database Syst Rev. 2000;(2):CD000067
references.pmid: 10796482
references.citation: Gastroenterology. 2000 Oct;119(4):895-902
references.pmid: 11040176
references.citation: Inflamm Bowel Dis. 2009 Mar;15(3):375-82
references.pmid: 19009634
references.citation: J Pediatr Gastroenterol Nutr. 2013 Aug;57(2):250-7
references.pmid: 23648790
references.citation: Cochrane Database Syst Rev. 2009 Jan 21;(1):CD000067
references.pmid: 19160175
references.citation: Inflamm Bowel Dis. 2008 Oct;14 Suppl 2:S9-11
references.pmid: 18816756
references.citation: Inflamm Bowel Dis. 2011 Jan;17(1):423-39
references.pmid: 20564651
references.citation: Gut. 1995 Nov;37(5):674-8
references.pmid: 8549944
references.citation: Clin Epidemiol. 2013 Dec 06;5:501-12
references.pmid: 24348071
references.citation: N Engl J Med. 2010 Apr 15;362(15):1383-95
references.pmid: 20393175
references.citation: Inflamm Bowel Dis. 2011 Oct;17(10):2138-43
references.pmid: 21910176
references.citation: Inflamm Bowel Dis. 2007 Jul;13(7):890-5
references.pmid: 17286275
references.citation: Inflamm Bowel Dis. 2006 Sep;12(9):831-6
references.pmid: 16954801
references.citation: J Pediatr Gastroenterol Nutr. 2009 Sep;49(3):297-303
references.pmid: 19590456
references.citation: Gastroenterology. 2000 Apr;118(4):705-13
references.pmid: 10734022
references.citation: Inflamm Bowel Dis. 2009 Apr;15(4):589-93
references.pmid: 18985746
references.citation: N Engl J Med. 1980 May 1;302(18):981-7
references.pmid: 6102739
references.citation: J Pediatr Gastroenterol Nutr. 2011 Jun;52(6):702-7
references.pmid: 21593643
references.citation: Pediatrics. 2012 Apr;129(4):e1030-41
references.pmid: 22412030
references.citation: Gastroenterology. 2012 Jan;142(1):46-54.e42; quiz e30
references.pmid: 22001864
references.citation: Clin Gastroenterol Hepatol. 2004 Sep;2(9):731-43
references.pmid: 15354273
references.citation: BMJ. 2002 Oct 26;325(7370):961-4
references.pmid: 12399352
references.citation: Dig Liver Dis. 2008 Oct;40(10):814-20
references.pmid: 18479986
references.citation: Am J Gastroenterol. 2008 Sep;103(9):2284-92
references.pmid: 18671816