Outcome of concomitant treatment with thiopurines and allopurinol in patients with inflammatory bowel disease: A nationwide Danish cohort study

United European Gastroenterol J. 2020 Feb;8(1):68-76. doi: 10.1177/2050640619868387. Epub 2019 Aug 3.

Abstract

Background: Thiopurine and allopurinol in combination are associated with clinical remission in inflammatory bowel diseases but their influence on subsequent outcomes is unclear. We compared outcomes during exposure to both thiopurines and allopurinol versus thiopurines alone.

Methods: We established a nationwide cohort of patients with inflammatory bowel diseases exposed to thiopurines ± allopurinol during 1999-2014, using registry data. Patients were followed until hospitalization, surgery, anti-TNFα, or death (as a primary composite outcome). We used Poisson regression analyses to calculate incidence rate ratios overall and stratified by calendar period (assuming the combined exposure was unintended before 2009).

Results: A total of 10,367 patients with inflammatory bowel diseases (Crohn's disease, n = 5484; ulcerative colitis, n = 4883) received thiopurines. Of these, 217 (2.1%) also received allopurinol. During 24,714 person years of follow-up, we observed 40 outcomes among thiopurine-allopurinol-exposed patients, and 4745 outcomes among those who were thiopurine exposed; incidence rate ratio, 1.26 (95% confidence interval, 0.92-1.73). The incidence rate ratios decreased over time: 4.88 (95% confidence interval 2.53-9.45) for 1999-2003, 2.19 (95% confidence interval, 1.17-4.09) for 2004-2008 and 0.80 (95% confidence interval, 0.52-1.23) for 2009-2014.

Conclusion: Our nationwide inflammatory bowel disease cohort study shows that concomitant thiopurine-allopurinol is as safe to use as thiopurines alone, with a tendency towards a positive effect on clinical outcomes in recent calendar periods when combined use was intended.

Keywords: Inflammatory bowel disease; allopurinol; anti-TNFα; epidemiology; hospitalization; surgery; thiopurine.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Allopurinol / administration & dosage*
  • Allopurinol / adverse effects
  • Azathioprine / administration & dosage*
  • Azathioprine / adverse effects
  • Azathioprine / pharmacokinetics
  • Colitis, Ulcerative / diagnosis
  • Colitis, Ulcerative / drug therapy*
  • Colitis, Ulcerative / immunology
  • Crohn Disease / diagnosis
  • Crohn Disease / drug therapy*
  • Crohn Disease / immunology
  • Denmark
  • Drug Therapy, Combination / adverse effects
  • Drug Therapy, Combination / methods
  • Female
  • Follow-Up Studies
  • Hospitalization / statistics & numerical data
  • Humans
  • Immunosuppressive Agents / administration & dosage*
  • Immunosuppressive Agents / adverse effects
  • Immunosuppressive Agents / pharmacokinetics
  • Male
  • Mercaptopurine / administration & dosage*
  • Mercaptopurine / adverse effects
  • Mercaptopurine / analogs & derivatives
  • Mercaptopurine / immunology
  • Mercaptopurine / metabolism
  • Mercaptopurine / pharmacokinetics
  • Middle Aged
  • Remission Induction / methods
  • Severity of Illness Index
  • Signal Transduction / drug effects
  • Signal Transduction / immunology
  • Thioguanine / immunology
  • Thioguanine / metabolism
  • Treatment Outcome

Substances

  • Immunosuppressive Agents
  • Allopurinol
  • 6-methylthiopurine
  • Mercaptopurine
  • Thioguanine
  • Azathioprine