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P230. Thiopurines prevent advanced colorectal neoplasia in patients with inflammatory bowel disease

F.D.M. van Schaik1, H.M. Smeets2, G.J.M.G. van der Heijden2, P.D. Siersema1, M.G.H. van Oijen1, B. Oldenburg1

1Department of Gastroenterology and Hepatology, University Medical Center Utrecht, Utrecht, The Netherlands; 2Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands

Background and Aims: Previous studies have reported a chemopreventive effect of 5-aminosalicylic acid (ASA) therapy for colorectal cancer (CRC) in patients with inflammatory bowel disease (IBD). This is supposed to be related to its anti-inflammatory and pro-apoptotic properties as well as its inhibitory effect on cell growth and survival. Thiopurines (azathioprine and 6-mercaptopurine) have also anti-inflammatory properties, but, in contrast, have been associated with an increased risk of developing malignant lymphoma and other malignancies. In the present study, the association between thiopurine and 5-ASA therapy and advanced neoplasia risk (high-grade dysplasia and colorectal cancer) was investigated in a large cohort of IBD patients in the Netherlands.

Methods: Patients with IBD were identified in an anonymized computerized database of one of the Dutch health insurance companies, including 1.2 million policyholders. From this database, information regarding type of drugs and number of dosages provided to patients were collected between January, 2001 and December, 2009. Each IBD patient was linked to the Dutch nationwide pathology archive (PALGA) to verify the IBD diagnosis and to determine whether a patient had developed advanced neoplasia. Cox proportional hazard regression analysis was used to calculate the risk of advanced neoplasia in patients with and without thiopurine or 5-ASA use.

Results: A total of 2605 patients with a confirmed IBD diagnosis were included in this study. Of these, 981 patients (38%) used 5-ASA, 315 patients (12%) used thiopurines, 459 patients (18%) used both 5-ASA and thiopurines and 850 patients (33%) used none of these drugs. No statistically significant differences were found for type of IBD, gender, age, duration of IBD and extent of IBD between these groups. Thirty-one patients (1%) developed advanced neoplasia during 16,568 person years of follow-up. Of these, 12 patients (39%) had used 5-ASA, 2 (7%) thiopurines and 1 (3%) both drugs. Increasing age and disease involvement of more than 50% of the colon were associated with an increased risk of developing advanced neoplasia (adjusted hazard ratio (HR) 1.07, 95% confidence interval (CI) 1.04–1.11 and adjusted HR 5.88, 95% CI 2.00–17.3, respectively). Thiopurine use was associated with a significantly decreased risk of developing advanced neoplasia (adjusted HR 0.10, 95% CI 0.01–0.73). 5-ASA therapy had also a protective effect on developing advanced neoplasia, but this was not statistically significant (adjusted HR 0.51, 95% CI 0.20–1.26).

Conclusion: Thiopurine use protects colitis patients against the development of advanced neoplasia. The effect of 5-ASA appeared to be less pronounced.