Lymphoproliferative disorders in patients receiving thiopurines for inflammatory bowel disease: a prospective observational cohort study
Lymphoproliferative disorders in patients receiving thiopurines for inflammatory bowel disease: a prospective observational cohort study
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DOI：
10.1016/s0140-6736(09)61302-7
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发表时间：
2009-11-07
期刊：
影响因子：
168.9
通讯作者：
Carrat, Fabrice
中科院分区：
文献类型：
--
作者：
Beaugerie, Laurent;Brousse, Nicole;Carrat, Fabrice
背景 关于接受硫嘌呤治疗炎症性肠病的患者淋巴增殖性疾病风险增加的报道存在争议。我们在一项前瞻性观察队列研究中评估了这一风险。方法 19486 名炎症性肠病患者，其中 11759 名（60.3%）患有克罗恩病，7727 名（39.7%）患有溃疡性结肠炎或未分类的炎症性肠病，被纳入由 680 名胃肠病学家组成的法国全国队列中，他们报告了治疗期间免疫抑制治疗的详细信息。 观察期、癌症病例和死亡人数。根据硫嘌呤暴露评估淋巴增殖性疾病的风险。中位随访时间为 35 个月 (IQR 29-40)。 结果 在基线时，5867 名患者 (30.1%) 正在接受硫嘌呤治疗，2809 名患者 (14.4%) 已停药，10810 名患者 (55.5%) 从未接受过硫嘌呤治疗。新增23例淋巴组织增生性疾病病例，其中霍奇金淋巴瘤1例，非霍奇金淋巴组织增生性疾病22例。接受硫嘌呤治疗的患者中，淋巴细胞增殖性疾病的发生率为每 1000 患者年 0.90 (95% CI 0.50-1.49) 患者年，停药患者中，淋巴增殖性疾病的发生率为 0.20/1000 (0.02-0.72) 患者年，从未接受过硫嘌呤治疗的患者中，淋巴增殖性疾病的发生率为 0.26/1000 (0.10-0.57) 患者年（p=0.0054）。接受硫嘌呤治疗的患者与从未接受过该药物治疗的患者之间发生淋巴增殖性疾病的多变量调整风险比为 5.28 (2.01-13.9, p=0.0007)。大多数与硫嘌呤暴露相关的病例与移植后疾病的病理范围相匹配。解释接受硫嘌呤治疗炎症性肠病的患者发生淋巴增殖性疾病的风险增加。
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 19486 patients with inflammatory bowel disease, of whom 11759 (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 10810 (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.