Safety and effectiveness of long-term allopurinol-thiopurine maintenance treatment in inflammatory bowel disease

Inflammatory Bowel Disease, 05/18/2012

Long–term combination therapy with allopurinol and low–dose thiopurines is an effective and well–tolerated treatment in inflammatory bowel disease (IBD) patients with a skewed thiopurine metabolism.

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 × 108 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 × 108 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.

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