Solid malignancies among etanercept-treated patients with granulomatosis with polyangiitis (Wegener's): long-term followup of a multicenter longitudinal cohort.
Solid malignancies among etanercept-treated patients with granulomatosis with polyangiitis (Wegener's): long-term followup of a multicenter longitudinal cohort.
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DOI：
10.1002/art.30394
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发表时间：
2011-08
影响因子：
--
通讯作者：
Specks, Ulrich
中科院分区：
文献类型：
--
作者：
Silva, Francisco;Seo, Philip;Schroeder, Darrell R.;Stone, John H.;Merkel, Peter A.;Hoffman, Gary S.;Spiera, Robert;Sebastian, Jodi K.;Davis, John C., Jr.;St Clair, E. William;Allen, Nancy B.;McCune, W. Joseph;Ytterberg, Steven R.;Specks, Ulrich
在韦格纳肉芽肿病依那西普试验(WGET)期间，观察到肿瘤坏死因子(TNF)的治疗抑制与实体恶性肿瘤之间的相关性。本研究旨在确定接受研究性治疗以外的恶性肿瘤风险。使用标准化数据表格确定实体恶性肿瘤的发生和类型。收集的数据包括生命状态、组织学报告和治疗干预。SEER数据库用于估计实体恶性肿瘤的标准化发病率(SIR)。153名患者(原始队列的85%)试验后可获得的中位随访期为43个月。其中50%的患者接受了依那西普治疗。依那西普组和安慰剂组之间的人口统计学没有差异。发现了13种新的实体恶性肿瘤，8种在依那西普组，5种在安慰剂组。依那西普组发生实体恶性肿瘤的风险高于普通人群(SIR=3.92；95%CI为1.69~7.72)，但与安慰剂组无差异(SIR=2.89；95%CI为0.94~6.73，P=0.39)。所有实体恶性肿瘤均发生在暴露于环磷酰胺的患者中。试验入选前的总病程和恶性肿瘤病史与试验后随访期间恶性肿瘤的发生有关。在WGET队列的长期随访期间，实体恶性肿瘤的发生率仍然增加。然而，这不能完全归因于试验期间接触依那西普。依那西普的抗肿瘤坏死因子治疗似乎进一步增加了接受细胞毒治疗的WG患者的恶性风险，应该避免在此类患者中使用。
An association between therapeutic inhibition of tumor necrosis factor (TNF) and solid malignancies was observed during the Wegener’s Granulomatosis Etanercept Trial (WGET). The present study was conducted to determine the malignancy risk beyond the exposure to study therapy. The occurrence and type of solid malignancies were ascertained using a standardized data form. Data collected included vital status, histologic reports, and therapeutic interventions. The SEER database was used to estimate a standardized incidence rate (SIR) for solid malignancies. The median post-trial follow-up available for 153 patients (85% of the original cohort) was 43 months. Fifty percent of these patients had received etanercept. There were no differences in demographics between etanercept and placebo groups. Thirteen new solid malignancies were detected, 8 in the etanercept and 5 in the placebo group. The risk of solid malignancies in the etanercept group was increased compared to the general population (SIR=3.92; 95% CI 1.69–7.72), but not different from that of the placebo group (SIR=2.89; 95% CI 0.94–6.73, p=0.39). All solid malignancies occurred in patients exposed to cyclophosphamide. The overall duration of disease and a history of malignancy before trial enrollment were associated with the development of malignancy during post-trial follow-up. The incidence of solid malignancy remained increased during long-term follow-up of the WGET cohort. However, this could not be attributed solely to etanercept exposure during the trial. Anti-TNF therapy with etanercept appears to further increase the risk of malignancy observed in patients with WG treated with cytotoxic therapy and should be avoided in such patients.
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影响因子：
4.7
作者：
Kermani, Tanaz A.;Schaefer, Valentin S.;Crowson, Cynthia S.;Hunder, Gene G.;Gabriel, Sherine E.;Ytterberg, Steven R.;Matteson, Eric L.;Warrington, Kenneth J.
通讯作者：
Warrington, Kenneth J.
影响因子：
--
作者：
Hellgren, Karin;Smedby, Karin E.;Askling, Johan
通讯作者：
Askling, Johan
影响因子：
10.3
作者：
GRIDLEY, G;MCLAUGHLIN, JK;FRAUMENI, JF
通讯作者：
FRAUMENI, JF
影响因子：
6.4
作者：
Knight, A;Askling, J;Ekbom, A
通讯作者：
Ekbom, A
影响因子：
--
作者：
Hopkins, J;Stone, JH;White, B
通讯作者：
White, B