title: Safety and effectiveness of long-term allopurinol-thiopurine maintenance treatment in inflammatory bowel disease.
abstract: BACKGROUND
  Thiopurines are the mainstay of conventional maintenance therapy in inflammatory bowel disease (IBD). Unfortunately, up to 50% of patients discontinue immunosuppressive therapy within 2 years due to intolerance or lack of efficacy. Allopurinol with low-dose thiopurine can optimize thiopurine metabolism for IBD patients with preferential shunting toward 6-methyl mercaptopurine (6-MMP) formation. The aim of this study was to assess long-term maintenance effectiveness and tolerability of allopurinol-thiopurine therapy in a larger multicenter cohort of IBD patients.
  
  
  METHODS
  Enrolled patients who failed monotherapy with thiopurines due to a skewed metabolism were subsequently treated with a combination therapy of allopurinol and low-dose thiopurine. Adverse events were monitored and therapeutic adherence was assessed. Seventy-seven IBD patients were enrolled with a mean follow-up of 19 months.
  
  
  RESULTS
  The median 6-thioguanine nucleotide concentration increased from 145 during monotherapy to 271 pmol/8 × 10(8) red blood cell (RBC) after at least 8 weeks of combination therapy while reducing the thiopurine dosage (P < 0.001). In contrast, median 6-MMP concentrations decreased from 10,110 to 265 pmol/8 × 10(8) RBC (P < 0.001). Leukopenia occurred in 12 patients (16%), requiring dose adaptation. Liver test abnormalities normalized in 81% of patients after the addition of allopurinol. Sixteen (21%) patients had to discontinue combination therapy. The percentage of patients still using combination therapy at 6, 12, 24, and 60 months was 87%, 85%, 76%, and 65%, respectively.
  
  
  CONCLUSIONS
  Long-term combination therapy with allopurinol and low-dose thiopurines is an effective and well-tolerated treatment in IBD patients with a skewed thiopurine metabolism.
authors.affiliation: Inflammatory Bowel Disease Center, University of Chicago, Chicago, Illinois, USA. frankhoentjen@gmail.com
authors.forename: Frank
authors.initials: F
authors.lastname: Hoentjen
authors.forename: Margien L
authors.initials: ML
authors.lastname: Seinen
authors.forename: Stephen B
authors.initials: SB
authors.lastname: Hanauer
authors.forename: Nanne K H
authors.initials: NK
authors.lastname: de Boer
authors.forename: David T
authors.initials: DT
authors.lastname: Rubin
authors.forename: Gerd
authors.initials: G
authors.lastname: Bouma
authors.forename: Laura E
authors.initials: LE
authors.lastname: Harrell
authors.forename: Adriaan A
authors.initials: AA
authors.lastname: van Bodegraven
mesh_terms: D000293:Adolescent; D000328:Adult; D000493:Allopurinol / Q000378:metabolism / Q000627:therapeutic use*; D001379:Azathioprine / Q000378:metabolism / Q000627:therapeutic use*; D003093:Colitis, Ulcerative / Q000188:drug therapy* / Q000378:metabolism; D003424:Crohn Disease / Q000188:drug therapy* / Q000378:metabolism; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000378:metabolism / Q000627:therapeutic use*; D060046:Maintenance Chemotherapy; D008297:Male; D055118:Medication Adherence; D015122:Mercaptopurine / Q000378:metabolism / Q000627:therapeutic use*; D008875:Middle Aged; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D007166:Immunosuppressive Agents; D000493:Allopurinol; D015122:Mercaptopurine; D001379:Azathioprine