title: Meta-analysis of risk of malignancy with immunosuppressive drugs in inflammatory bowel disease.
abstract: BACKGROUND
  There is a concern as to whether long-term administration of immunosuppressants in patients with inflammatory bowel disease (IBD) would increase the risk of malignancy.
  
  
  OBJECTIVE
  To compare the risks of developing malignancy between patients with IBD treated with immunosuppressive agents and patients with IBD not receiving these agents.
  
  
  METHODS
  A systematic literature review was conducted, and a meta-analysis was performed on data retrieved from cohort studies that followed patients with IBD who received immunosuppressive agents for more than a year and documented the incidence of newly developed malignancy. An electronic search was conducted using MEDLINE (1966-September 2006), the Cochrane Library (issue 3, 2006), and Japana Centra Revuo Medicina (1981-September 2006). Medical subject headings used in the searches were azathioprine, 6-mercaptopurine, cyclosporine, methotrexate, tacrolimus, inflammatory bowel disease, and neoplasms. We imposed no language limitation in the searches. Additionally, a manual search of reference listings from all articles retrieved from the electronic databases was performed. Using data obtained from control groups or population-based studies, the incidence of newly developed malignancy in patients with IBD treated with immunosuppressive agents was compared with that of patients with IBD who were not receiving immunosuppressive agents. Statistical analysis for the change in risk of developing malignancy was performed using the weighted mean difference (WMD) normalized to per person-year and its 95% confidence interval.
  
  
  RESULTS
  Nine cohort studies met the inclusion criteria for this meta-analysis. Analysis of these studies showed no discernible difference (WMD -0.3 x 10(-3)/person-year; 95% CI -1.2 x 10(-3) to 0.7 x 10(-3)) in the incidence of any kind of malignancy in patients with IBD who received immunosuppressants compared with those who did not receive immunosuppressants. No significant difference in WMD was observed when the data from patients with either Crohn's disease (CD) or ulcerative colitis (UC) were analyzed separately.
  
  
  CONCLUSIONS
  Our findings suggest that the administration of immunosuppressive agents in patients with either CD or UC probably does not confer a significantly increased risk of malignancy compared with patients with IBD who are not receiving these agents.
authors.affiliation: Student, Graduate School of Pharmaceutical Sciences, Department of Pharmacy, Hatsudai Rehabilitation Hospital, Tokyo.
authors.forename: Yukari
authors.initials: Y
authors.lastname: Masunaga
authors.forename: Keiko
authors.initials: K
authors.lastname: Ohno
authors.forename: Ryuichi
authors.initials: R
authors.lastname: Ogawa
authors.forename: Masayuki
authors.initials: M
authors.lastname: Hashiguchi
authors.forename: Hirotoshi
authors.initials: H
authors.lastname: Echizen
authors.forename: Hiroyasu
authors.initials: H
authors.lastname: Ogata
mesh_terms: D015331:Cohort Studies; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects*; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy / Q000453:epidemiology*; D009369:Neoplasms / Q000139:chemically induced* / Q000453:epidemiology*; D012307:Risk Factors
chemical_list: D007166:Immunosuppressive Agents