Anti-tumour necrosis factor therapy in rheumatoid arthritis and risk of malignant lymphomas: relative risks and time trends in the Swedish Biologics Register
Anti-tumour necrosis factor therapy in rheumatoid arthritis and risk of malignant lymphomas: relative risks and time trends in the Swedish Biologics Register
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DOI：
10.1136/ard.2007.085852
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发表时间：
2009-05-01
影响因子：
27.4
通讯作者：
Feltelius, N.
中科院分区：
文献类型：
--
作者：
Askling, J.;Baecklund, E.;Feltelius, N.
背景：肿瘤坏死因子拮抗剂已被证明是治疗类风湿性关节炎(RA)的有效药物，但抗肿瘤坏死因子治疗是否增加了类风湿关节炎中已经增加的淋巴瘤风险这一悬而未决的问题仍然是一个令人担忧的问题。方法：利用瑞典生物学登记(ARTIS)、瑞典癌症登记、先前存在的RA队列以及与其他国家健康和人口普查登记机构的交叉链接，建立了一个全国性的RA队列(n=67743)，并确定了在1998年至2006年7月开始抗肿瘤坏死因子治疗的患者(n=6604)。结果：在6604例接受抗肿瘤坏死因子治疗的类风湿关节炎患者中，26例恶性淋巴瘤发生在26 981人年中，其相对危险度(RR)分别为1.35(95%CI 0.82~2.11)和2.72(95%CI 1.82~4.08)；与一般人群对照(3355 849人年中发生1568例淋巴瘤)。在1998-2001年间开始抗肿瘤坏死因子治疗的RA患者，与两个对照组相比，淋巴瘤风险全部增加。相反，从第一次治疗开始至今，RR并不随治疗时间或治疗累积时间的变化而显著变化，也不随抗肿瘤坏死因子药物的类型而变化。结论：总的来说，在治疗类风湿性关节炎的常规护理中，肿瘤坏死因子拮抗剂与类风湿性关节炎已经升高的淋巴瘤发生率的进一步增加无关。选择治疗患者的变化可能会影响观察到的风险。
Background: Tumour necrosis factor (TNF) antagonists have proved effective as treatment against rheumatoid arthritis ( RA), but the unresolved issue of whether the use of anti-TNF therapy increases the already elevated risk of lymphoma in RA remains a concern.Methods: Using the Swedish Biologics Register (ARTIS), the Swedish Cancer Register, pre-existing RA cohorts and cross-linkage with other national health and census registers, a national RA cohort (n = 67 743) was assembled and patients who started anti-TNF therapy between 1998 and July 2006 ( n = 6604) were identified. A general population comparator ( n = 471 024) was also assembled and the incidence of lymphomas from 1999 to 31 December 2006 was assessed and compared in these individuals.Results: Among the 6604 anti-TNF-treated RA patients, 26 malignant lymphomas were observed during 26 981 person-years of follow-up, which corresponded to a relative risk (RR) of 1.35 (95% CI 0.82 to 2.11) versus anti-TNF-naive RA patients ( 336 lymphomas during 365 026 person-years) and 2.72 ( 95% CI 1.82 to 4.08) versus the general population comparator ( 1568 lymphomas during 3 355 849 person-years). RA patients starting anti-TNF therapy in 1998-2001 accounted for the entire increase in lymphoma risk versus the two comparators. By contrast, RR did not vary significantly by time since start of first treatment or with the accumulated duration of treatment, nor with the type of anti-TNF agent.Conclusion: Overall and as used in routine care against RA, TNF antagonists are not associated with any major further increase in the already elevated lymphoma occurrence in RA. Changes in the selection of patients for treatment may influence the observed risk.