Reduced Risk of Inflammatory Bowel Disease-associated Colorectal Neoplasia with Use of Thiopurines: a Systematic Review and Meta-analysis

J Crohns Colitis. 2018 Apr 27;12(5):546-558. doi: 10.1093/ecco-jcc/jjy006.

Abstract

Background and aims: The association between thiopurines and colorectal neoplasia risk remains controversial in inflammatory bowel disease [IBD] patients. We performed a systematic review and meta-analysis examining this association.

Methods: A comprehensive search of the PubMed, EMBASE and Cochrane Library databases was performed to identify relevant literature. Random-effects models were applied to calculate the pooled odds ratio [OR] and relative risk [RR] with corresponding 95% confidence intervals [CIs] among case-control and cohort studies.

Results: Eleven cohort and 16 case-control studies involving 95397 patients were included in this study. Overall, the use of thiopurines was associated with a reduced risk of colorectal neoplasia both in case-control [OR = 0.49, 95% CI: 0.34-0.70] and cohort studies [RR = 0.96, 95% CI: 0.94-0.98]. Moreover, a protective effect of thiopurines against advanced neoplasia [high-grade dysplasia and cancer] [OR = 0.51, 95% CI: 0.31-0.84 for case-control studies; RR = 0.96, 95% CI: 0.94-0.98 for cohort studies] and colorectal cancer [CRC] [OR = 0.56, 95% CI: 0.34-0.93 for case-control studies; RR = 0.96, 95% CI: 0.94-0.98 for cohort studies] was also observed. Furthermore, when the analysis was conducted on patients at a high risk for colorectal neoplasia, the chemopreventive effect was confirmed in patients with long disease duration [> 8 years] but not in those with extensive colitis or primary sclerosing cholangitis.

Conclusions: This study demonstrated that thiopurine use was associated with a reduced risk of colorectal neoplasia, advanced neoplasia and CRC in IBD patients, especially those with long disease duration [> 8 years].

Publication types

  • Meta-Analysis
  • Review
  • Systematic Review

MeSH terms

  • Colorectal Neoplasms / epidemiology*
  • Colorectal Neoplasms / etiology
  • Humans
  • Immunosuppressive Agents / therapeutic use*
  • Incidence
  • Inflammatory Bowel Diseases / complications
  • Inflammatory Bowel Diseases / drug therapy*
  • Mercaptopurine / analogs & derivatives*
  • Mercaptopurine / therapeutic use*
  • Protective Factors
  • Risk Factors

Substances

  • Immunosuppressive Agents
  • azathiopurine
  • Mercaptopurine