Risk of Lymphoma in Patients with Ulcerative Colitis Treated with Thiopurines—a Nationwide Retrospective Cohort Study
Menée à partir des données du système de santé des anciens combattants américains portant sur 36 891 patients atteints de rectocolite hémorragique (durée médiane de suivi : 6,7 ans), cette étude évalue l'association entre l'utilisation de thiopurines pour traiter la maladie et le risque de lymphome (23 cas sur 4 734 patients utilisant les thiopurines ou ayant arrêté de les utiliser)
Background & Aims : There is controversy over whether treatment of patients ulcerative colitis (UC) with thiopurines increases their risk of lymphoma. We evaluated the risk of lymphoma (ongoing, residual, and per year of therapy) among thiopurine-treated patients with UC. Methods : We obtained nationwide data from the Veterans Affairs (VA) healthcare system, from 2001 through 2011. We performed a retrospective cohort study, analyzing data from 36,891 patients with UC from their date of diagnosis at the VA until a diagnosis of lymphoma or October, 1st, 2011 (subjects followed for a median of 6.7 y). Thiopurine exposure was assessed from the VA pharmacy database. Patients who developed lymphoma were identified based on ICD-9 codes and confirmed by manual chart review. Results : Of the patients with UC, 4 734 (13%) used thiopurines for a median of 1 y. Lymphomas developed in 119 patients who had not taken thiopurines, 18 who were taking the drugs, and 5 who had stopped taking them. The incidence rates of lymphoma were 0.60 per 1000 person-y among patients who had not taken thiopurines, 2.31 among patients taking the drugs, and 0.28 among patients who had stopped taking them. The incidence rates of lymphoma during the 1st y, 2nd y, 3rd y, 4th y, and >4 y of thiopurine therapy were 0.9, 1.6, 1.6, 5, and 8.9 per 1000 person-years, respectively. The age-, sex- and race-adjusted hazard ratios of developing lymphoma were 4.2 (95% confidence interval, 2.5–6.8; P<.0001) while on thiopurines and 0.5 (95% confidence interval, 0.2–1.3; P=.17) after stopping them, compared to patients who had not taken thiopurines. Conclusions : Based on a retrospective, nationwide cohort study, patients with UC have a 4-fold increase in risk of lymphoma while taking thiopurines, compared with patients who have not taken these drugs. The risk increased gradually for successive ys of therapy. Stopping thiopurine therapy reduces risk of lymphoma.
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