Tumor necrosis factor antagonist therapy and lymphoma development - Twenty-six cases reported to the Food and Drug Administration
Tumor necrosis factor antagonist therapy and lymphoma development - Twenty-six cases reported to the Food and Drug Administration
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DOI：
10.1002/art.10679
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发表时间：
2002-12-01
影响因子：
--
通讯作者：
Braun, MM
中科院分区：
文献类型：
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作者：
Brown, SL;Greene, MH;Braun, MM
目标。依那西普和英夫利昔单抗是肿瘤坏死因子(TNF)拮抗剂，最近被批准用于治疗类风湿性关节炎(RA)和克罗恩病(CD)。本研究旨在调查接受这些药物治疗的患者中淋巴增生性疾病的发生情况。对美国食品和药物管理局运行的MedWatch上市后不良事件监测系统的相关数据进行回顾。在依那西普(18例)或英夫利昔单抗(8例)治疗后，我们发现了26例淋巴增生性疾病。大多数病例(81%)为非霍奇金淋巴瘤。开始使用依那西普或英夫利昔单抗治疗至发生淋巴瘤的间隔非常短(中位数为8周)。在2例(英夫利昔单抗，1例依那西普)中，在没有针对淋巴瘤的特定细胞毒治疗的情况下，在停止抗肿瘤坏死因子治疗后观察到淋巴瘤消退。尽管像这样的病例系列数据不能确定暴露于这些药物与淋巴增殖性疾病风险之间的明确因果关系，但已知的RA和CD患者对淋巴瘤的易感性、其他免疫抑制人群中已知的过多的淋巴瘤以及已知的抗肿瘤坏死因子药物的免疫抑制作用为启动额外的流行病学研究以正式评估这种可能的联系提供了生物学基础和理由。
Objective. Etanercept and infliximab are tumor necrosis factor (TNF) antagonists that have been recently approved for the treatment of rheumatoid arthritis (RA) and Crohn's disease (CD). This study was undertaken to investigate the occurrence of lymphoproliferative disorders in patients treated with these agents.Methods. Relevant data in the MedWatch post-market adverse event surveillance system run by the US Food and Drug Administration were reviewed.Results. We identified 26 cases of lymphoproliferative disorders following treatment with etanercept (18 cases) or infliximab (8 cases). The majority of cases (81%) were non-Hodgkin's lymphomas. The interval between initiation of therapy with etanercept or infliximab and the development of lymphoma was very short (median 8 weeks). In 2 instances (I infliximab, 1 etanercept), lymphoma regression was observed following discontinuation of anti-TNF treatment, in the absence of specific cytotoxic therapy directed toward the lymphoma.Conclusion. Although data from a case series such as this cannot establish a clear causal relationship between exposure to these medications and the risk of lymphoproliferative disease, the known predisposition of patients with RA and CD to lymphoma, the known excess of lymphoma in other immunosuppressed populations, and the known immunosuppressive effects of the anti-TNF drugs provide a biologic basis for concern and justification for the initiation of additional epidemiologic studies to formally evaluate this possible association.