Résumé
Rationnel
Les données sur le sur-risque de lymphome chez les patients traités par thiopurine pour maladie inflammatoire chronique intestinale sont controversées. Nous avons établi ce risque dans une étude de cohorte observationnelle prospective.
Méthode
19 486 patients avec maladie inflammatoire chronique intestinale, dont 11,759 (60,3%) maladies de Crohn et 7727 (39,7%) rectocolites hémorragiques ou colites indéterminées ont été inclus dans une cohorte nationale française par 680 gastro-entérologues qui renseignaient en détail le traitement immunosuppresseur, les cas de cancer et les décès durant toute la période de suivi. Le risque de lymphome était évalué en fonction de l’exposition aux thiopurines. Le suivi médian était de 35 mois (IQR 29–40).
Résultats
A l’inclusion, 5 867 (30,1%) patients recevaient une thiopurine, 2 809 (14,4%) avaient arrêté un traitement par thiopurine et 10 810 (55,5%) n’avaient jamais reçu de thiopurine. 23 lymphomes de novo ont été diagnostiqués : il s’agissait d’un cas de maladie de Hodgkin, et 22 cas de lymphomes non Hodgkininens. Le taux d’incidence de lymphome était de 0,90 (95% CI 0,50–1,49) pour 1 000 patients-année chez ceux ayant une thiopurine, 0,20/1000 (0,02–0,72) patients-année chez ceux ayant arrêté les thiopurines, et 0,26/1000 (0,10–0,57) patients-année chez ceux n’ayant jamais reçu de thiopurine (p=0,0054). Le risque relatif en analyse multivariée de lymphome était de 5,28 (2,01–13,9, p=0,0007) entre les patients ayant un traitement par thiopurine et ceux n’ayant jamais reçu de thiopurine. La plupart des cas survenus sous thiopurines partageaient les caractéristiques des lymphomes post-transplantation.
Interprétation
Les patients qui reçoivent des thiopurines pour maladie inflammatoire chronique intestinale ont un risque accru de lymphome.
Abstract
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 7,727 (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, 5,867 (30.1%) of patients were receiving, 2,809 (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 1,000 (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 multivariateadjusted 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.
Références
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Simon, M. Désordres lympho-prolifératifs chez les patients traités par thiopurine pour maladies inflammatoires chroniques intestinales : étude de cohorte observationnelle prospective nationale. Colon Rectum 8, 165–167 (2014). https://doi.org/10.1007/s11725-014-0528-4
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DOI: https://doi.org/10.1007/s11725-014-0528-4