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15. Risk of squamous and basal cell carcinomas in patients with inflammatory bowel disorders exposed to thiopurines: The Cesame National Cohort Study

L. Peyrin-Biroulet1, K. Khosrotehrani2, F. Carrat3, A. Bouvier4, J. Chevaux1, F. Carbonnel5, J. Colombel6, J. Dupas7, P. Godeberge8, J. Hugot9, M. Lémann10, S. Nahon11, J. Sabaté12, G. Tucat13, L. Beaugerie2

1Inserm U954, University Hospital of Nancy, Vandoeuvre-lès-Nancy, France; 2Saint-Antoine Hospital, Paris, France; 3University Pierre and Marie Curie, Paris, France; 4University of Bourgogne, Dijon, France; 5University Hospital of Bicêtre, Paris, France; 6University Hospital of Lille, Lille, France; 7University Hospital of Amiens, Amiens, France; 8Institut mutualiste Montsouris, Paris, France; 9Robert Debré Hospital, Paris, France; 10Saint Louis Hospital, Paris, France; 11Montfermeil Hospital, Paris, France; 12Louis Mourier Hospital, Paris, France; 13Clinic of Trocadero, Paris, France

Background: The potential responsibility of thiopurines in promoting skin carcinomas remains controversial among patients with inflammatory disorders as opposed to solid organ recipients.

Objective: To assess the role of thiopurines in promoting skin carcinomas in a prospective cohort of patients with inflammatory bowel disease (IBD).

Patients and Methods: 19,486 patients with IBD (60.3% Crohn's disease, 39.7% ulcerative colitis) were enrolled in a nationwide French cohort. Details of immunosuppressive therapy and cases of cancer were reported. Median follow-up was 35 months (IQR: 29–40). The risk of skin carcinomas was assessed according to thiopurine exposure.

Results: At baseline, 5,867 (30.1%) of patients were receiving, 2,809 (14.4%) had discontinued, and 10,810 had never received thiopurines. Thirty-two cases of skin carcinomas were recorded (20 basal and 12 squamous cell carcinomas). Before the age of 50, the incidence of skin carcinomas among patients receiving thiopurine therapy and those previously exposed was 0.59 (95% CI: 0.25–1.16) and 0.50 (95% CI: 0.14–1.29) per 10,000 patient-years, respectively. The incidence of skin carcinomas was nil in patients who never received thiopurines. Similar differences in skin carcinoma incidence according to exposure to thiopurines were observed in patients between 50–65 and over 65 years of age. In a nested case–control study adjusted for propensity to receive thiopurines, ongoing thiopurine treatment (OR: 7.3; 95% CI: 2.7–19.8; p = 0.0001), past exposure to thiopurines (OR: 5.1; 95% CI: 1.7–15.3; p = 0.004) and age (OR: 1.1; 95% CI: 1.04–1.09; p < 0.0001) were independent risk factors for skin carcinomas. Similar results were obtained when considering squamous and basal cell carcinomas separately.

Conclusion: Present and past exposure to thiopurines significantly increase the risk of skin carcinomas in patients with IBD. This increased risk is already present before the age of 50. These results strongly support sun protection and dermatological screening in these patients.