Thiopurines and risk of nonmelanoma skin cancer in inflammatory bowel disease.

Questions: Is there an increased risk of nonmelanoma skin cancer (NMSC) for patients with inflammatory bowel disease (IBD)? Is there an increased risk of NMSC if they receive immunosuppressive therapy? Design: Historical cohort study and nested case-control study. Setting: Data were obtained from the Manitoba Health administrative databases and the Manitoba Cancer Registry. Patients: For the cohort study, patients had IBD before March 31, 2008 (defined by 5 physician contacts or hospitalizations for IBD, or 3 contacts if 2 years of information were available, without previous history of malignancy before the IBD diagnosis; median age, 36 years; patients were matched to controls by age, sex, and location). For the nested case-control study, patients had IBD diagnosed with NMSC between 1997 and 2009. Immunosuppressant medication users were defined as receiving 2 or more prescriptions for any immunosuppressant medication during follow-up. Intervention: For the cohort study, patients were watched from the date of IBD diagnosis until a diagnosis of invasive cancer, death, migration from the study area, or end of study (December 31, 2009). Cox regression analysis was performed on the data. For the nested case-control study, IBD patients with NMSC were included from the cohort study and separated according to exposure to immunosuppressant medications. Data were analyzed with incidence density and conditional logistic regression analysis and were adjusted for number of physician visits and socioeconomic status (SES). Outcome Measures: For the cohort study, the incidence of NMSC was analyzed as identified by the Manitoba Cancer Registry with the International Classification of Diseases, Ninth Revision. For the case-control study, the amount and type of exposure to immunosuppressants were investigated. Results: A total of 9618 patients with IBD were followed for a median of 11.7 years, and 91 378 controls without IBD for a median of 11.5 years. Univariate analysis revealed an increased risk of NMSC among IBD patients compared with controls (hazard ratio [HR], 1.25; 95% CI, 1.09-1.43). Adjustment for SES and health care use yielded a nonsignificant increase in risk of NMSC in IBD (HR, 1.14; 95% CI, 0.99-1.32). Basal cell carcinoma (BCC) constituted the majority of NMSC diagnoses. In stratification analysis, patients with IBD (compared with controls) had an increased risk of BCC (HR, 1.20; 95% CI, 1.03-1.40). Use of thiopurines in IBD patients increased their risk of squamous cell carcinoma (SCC) (HR, 5.40; 95% CI, 2.00-14.56). In the case-control study, among persons with IBD, use of immunosuppressants was associated with NMSC, (odds ratio [OR], 1.83; 95% CI, 1.09-3.05) and use of thiopurines with SCC (OR, 20.52; 95% CI, 2.42-173.81). Conclusions: Among IBD patients, the risk of BCC may be increased, and with use of thiopurines, the risk of SCC is increased.