Association between thiopurine use and nonmelanoma skin cancers in patients with inflammatory bowel disease: a meta-analysis

Am J Gastroenterol. 2014 Feb;109(2):163-9. doi: 10.1038/ajg.2013.451. Epub 2014 Jan 14.

Abstract

Objectives: Thiopurines are the mainstay of treatment for patients with inflammatory bowel disease (IBD). Thiopurine therapy increases the risk of nonmelanoma skin cancers (NMSCs) in organ transplant patients. The data on NMSC in patients with IBD on thiopurines is conflicting.

Methods: We searched electronic databases for full journal articles reporting on the risk of developing NMSC in patients with IBD on thiopurine and hand searched the reference lists of all retrieved articles. Pooled adjusted hazard ratios and 95% confidence intervals (CIs) were determined using a random-effects model. Publication bias was assessed using Funnel plots and Egger's test. Heterogeneity was assessed using Cochran's Q and the I(2) statistic.

Results: Eight studies involving 60,351 patients provided data on the risk of developing NMSC in patients with IBD on thiopurines. The pooled adjusted hazards ratio of developing NMSC after exposure to thiopurines in patients with IBD was 2.28 (95% CI: 1.50 to 3.45). There was significant heterogeneity (I(2)=76%) between the studies but no evidence of publication bias. Meta regression analysis suggested that the population studied (hospital-based vs. population-based) and duration of follow-up contributed significantly to heterogeneity. Grouping studies based on population studied and duration showed higher hazard rations in hospital-based and shorter duration studies.

Conclusions: The risk of developing NMSC in patients with IBD on thiopurines is only modestly elevated. The difference in pooled risk between population-based and hospital-based studies suggests the possibility that ascertainment bias could have contributed to this increased risk.

Publication types

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

MeSH terms

  • Carcinoma, Basal Cell / chemically induced
  • Carcinoma, Basal Cell / epidemiology
  • Carcinoma, Squamous Cell / chemically induced
  • Carcinoma, Squamous Cell / epidemiology
  • Cohort Studies
  • Confidence Intervals
  • Databases, Factual
  • Education, Medical, Continuing
  • Female
  • Humans
  • Immunosuppressive Agents / adverse effects*
  • Immunosuppressive Agents / therapeutic use
  • Incidence
  • Inflammatory Bowel Diseases / diagnosis
  • Inflammatory Bowel Diseases / drug therapy*
  • Male
  • Mercaptopurine / adverse effects*
  • Mercaptopurine / therapeutic use
  • Prognosis
  • Proportional Hazards Models
  • Regression Analysis
  • Risk Assessment
  • Skin Neoplasms / chemically induced*
  • Skin Neoplasms / epidemiology
  • Skin Neoplasms / pathology*
  • United Kingdom

Substances

  • Immunosuppressive Agents
  • Mercaptopurine