Systematic review with meta-analysis: thiopurines decrease the risk of colorectal neoplasia in patients with inflammatory bowel disease

Aliment Pharmacol Ther. 2018 Feb;47(3):318-331. doi: 10.1111/apt.14436. Epub 2017 Dec 4.

Abstract

Background: Patients with inflammatory bowel disease (IBD) have a high risk of developing colorectal neoplasia.

Aim: To investigate whether thiopurines can decrease the risk of developing colorectal neoplasia in patients with ulcerative colitis (UC) or Crohn's disease (CD).

Methods: We conducted a meta-analysis of 24 observational studies involving 76,999 participants to evaluate the risks of developing colorectal neoplasia in IBD patients receiving thiopurine treatment. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) for the risks of colorectal neoplasia were calculated using a random-effects model.

Results: The overall pooled estimate revealed a protective effect of thiopurine use on colorectal neoplasia in patients with IBD (OR = 0.63, 95% CI 0.46-0.86). The effect was significant in UC patients (OR = 0.67, 95% CI 0.45-0.98), but was not significant in CD patients (OR = 1.06, 95% CI 0.54-2.09). Thiopurines exposure significantly decreased the risk of colorectal cancer (CRC) (OR = 0.65, 95% CI 0.45-0.96) and advanced colorectal neoplasia (CRC and/or high-grade dysplasia) (OR = 0.62, 95% CI 0.44-0.89), but did not decrease the risk of dysplasia alone (OR = 0.90, 95% CI 0.37-2.21). Tendencies towards the protective effect of thiopurines were distinct in clinic-based studies (OR = 0.59, 95% CI 0.42-0.82) and case-control studies (OR = 0.40, 95% CI 0.26-0.62), but not in population-based studies (OR = 0.95, 95% CI 0.55-1.62) and cohort studies (OR = 0.98, 95% CI 0.81-1.18). Interestingly, studies conducted in Europe (OR = 0.48, 95% CI 0.31-0.77), rather than in North America (OR = 0.91, 95% CI 0.67-1.24), showed the protective effect of thiopurines.

Conclusions: This meta-analysis revealed an antineoplastic effect of thiopurines on colorectal neoplasia in patients with IBD, particularly amongst patients with UC.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't
  • Systematic Review

MeSH terms

  • Case-Control Studies
  • Chemoprevention / methods
  • Colorectal Neoplasms / etiology
  • Colorectal Neoplasms / prevention & control*
  • Humans
  • Inflammatory Bowel Diseases / complications
  • Inflammatory Bowel Diseases / drug therapy*
  • Inflammatory Bowel Diseases / pathology
  • Purines / therapeutic use*
  • Risk Factors
  • Sulfhydryl Compounds / therapeutic use*

Substances

  • Purines
  • Sulfhydryl Compounds