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.
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).
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.
Patients receiving thiopurines for inflammatory bowel disease have an increased risk
of developing lymphoproliferative disorders.
Programme Hospitalier de Recherche Clinique National (AOM05157), Association François
Aupetit, Délégation Inter-régionale de la Recherche clinique Ile de France-Assistance
Publique Hôpitaux de Paris (AP-HP), Ligue contre le Cancer, and Fonds de Recherche
de la Société Nationale Française de Gastro-entérologie.