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

Frank Hoentjen, Margien L. Seinen, Stephen B. Hanauer, Nanne K H De Boer, David T. Rubin, Gerd Bouma, Laura E. H. Raffals, Adriaan A. Van Bodegraven

Research output: Contribution to journalArticle

66 Citations (Scopus)

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 · 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. 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.

Original languageEnglish (US)
Pages (from-to)363-369
Number of pages7
JournalInflammatory Bowel Diseases
Volume19
Issue number2
DOIs
StatePublished - Feb 1 2013
Externally publishedYes

Fingerprint

Allopurinol
Inflammatory Bowel Diseases
Safety
Therapeutics
6-Mercaptopurine
Erythrocytes
Leukopenia
Immunosuppressive Agents

Keywords

  • 6-mercaptopurine
  • Allopurinol
  • Azathioprine
  • Crohn's disease
  • Inflammatory bowel disease
  • Therapeutic drug monitoring
  • Thiopurines
  • TPMT
  • Ulcerative colitis

ASJC Scopus subject areas

  • Gastroenterology
  • Immunology and Allergy

Cite this

Hoentjen, F., Seinen, M. L., Hanauer, S. B., De Boer, N. K. H., Rubin, D. T., Bouma, G., ... Van Bodegraven, A. A. (2013). Safety and effectiveness of long-term allopurinol-thiopurine maintenance treatment in inflammatory bowel disease. Inflammatory Bowel Diseases, 19(2), 363-369. https://doi.org/10.1002/ibd.23021

Safety and effectiveness of long-term allopurinol-thiopurine maintenance treatment in inflammatory bowel disease. / Hoentjen, Frank; Seinen, Margien L.; Hanauer, Stephen B.; De Boer, Nanne K H; Rubin, David T.; Bouma, Gerd; Raffals, Laura E. H.; Van Bodegraven, Adriaan A.

In: Inflammatory Bowel Diseases, Vol. 19, No. 2, 01.02.2013, p. 363-369.

Research output: Contribution to journalArticle

Hoentjen, F, Seinen, ML, Hanauer, SB, De Boer, NKH, Rubin, DT, Bouma, G, Raffals, LEH & Van Bodegraven, AA 2013, 'Safety and effectiveness of long-term allopurinol-thiopurine maintenance treatment in inflammatory bowel disease', Inflammatory Bowel Diseases, vol. 19, no. 2, pp. 363-369. https://doi.org/10.1002/ibd.23021
Hoentjen, Frank ; Seinen, Margien L. ; Hanauer, Stephen B. ; De Boer, Nanne K H ; Rubin, David T. ; Bouma, Gerd ; Raffals, Laura E. H. ; Van Bodegraven, Adriaan A. / Safety and effectiveness of long-term allopurinol-thiopurine maintenance treatment in inflammatory bowel disease. In: Inflammatory Bowel Diseases. 2013 ; Vol. 19, No. 2. pp. 363-369.
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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 · 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. 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.",
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AU - Rubin, David T.

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