Lymphoproliferative disorders in patients receiving thiopurines for inflammatory bowel disease: a prospective observational cohort study.
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Date publication
novembre 2009
Auteurs
Membres identifiés du Cancéropôle Est :
Dr BOUVIER Anne-Marie, Pr MAYNADIE Marc
Tous les auteurs :
Beaugerie L, Brousse N, Bouvier AM, Colombel JF, Lemann M, Cosnes J, Hebuterne X, Cortot A, Bouhnik Y, Gendre JP, Simon T, Maynadie M, Hermine O, Faivre J, Carrat F
Lien Pubmed
Résumé
BACKGROUND: Reports of an increased risk of lymphoproliferative disorders in patients receiving thiopurines for inflammatory bowel disease are controversial. We assessed this risk in a prospective observational cohort study. METHODS: 19,486 patients with inflammatory bowel disease, of whom 11,759 (60.3%) had Crohn's disease and 7727 (39.7%) had ulcerative colitis or unclassified inflammatory bowel disease, were enrolled in a nationwide French cohort by 680 gastroenterologists, who reported details of immunosuppressive therapy during the observation period, cases of cancer, and deaths. The risk of lymphoproliferative disorder was assessed according to thiopurine exposure. Median follow-up was 35 months (IQR 29-40). FINDINGS: At baseline, 5867 (30.1%) of patients were receiving, 2809 (14.4%) had discontinued, and 10,810 (55.5%) had never received thiopurines. 23 new cases of lymphoproliferative disorder were diagnosed, consisting of one case of Hodgkin's lymphoma and 22 cases of non-Hodgkin lymphoproliferative disorder. The incidence rates of lymphoproliferative disorder were 0.90 per 1000 (95% CI 0.50-1.49) patient-years in those receiving, 0.20/1000 (0.02-0.72) patient-years in those who had discontinued, and 0.26/1000 (0.10-0.57) patient-years in those who had never received thiopurines (p=0.0054). The multivariate-adjusted hazard ratio of lymphoproliferative disorder between patients receiving thiopurines and those who had never received the drugs was 5.28 (2.01-13.9, p=0.0007). Most cases associated with thiopurine exposure matched the pathological range of post-transplant disease. INTERPRETATION: Patients receiving thiopurines for inflammatory bowel disease have an increased risk of developing lymphoproliferative disorders. FUNDING: Programme Hospitalier de Recherche Clinique National (AOM05157), Association Francois Aupetit, Delegation Inter-regionale de la Recherche clinique Ile de France-Assistance Publique Hopitaux de Paris (AP-HP), Ligue contre le Cancer, and Fonds de Recherche de la Societe Nationale Francaise de Gastro-enterologie.
Référence
Lancet. 2009 Nov 7;374(9701):1617-25.