Divergent prognostic effects of pre-existing and treatment-emergent thyroid dysfunction in patients treated with immune checkpoint inhibitors.
Divergent prognostic effects of pre-existing and treatment-emergent thyroid dysfunction in patients treated with immune checkpoint inhibitors.
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DOI：
10.1007/s00262-022-03151-2
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发表时间：
2022-09
影响因子：
5.8
通讯作者：
Gerber, David E.
中科院分区：
文献类型：
--
作者：
von Itzstein, Mitchell S.;Gonugunta, Amrit S.;Wang, Yiqing;Sheffield, Thomas;Lu, Rong;Ali, Sadia;Fattah, Farjana J.;Xie, Donglu;Cai, Jennifer;Xie, Yang;Gerber, David E.
关键词：
甲状腺功能障碍是最常见的自身免疫性疾病和免疫检查点抑制剂（ICI）诱导的免疫相关不良事件（irAE）之一。我们确定了ICI治疗患者的纵向甲状腺功能和临床结果之间的关系。我们确定了2011年1月1日至2020年12月31日在UT西南医学中心接受ICI治疗的所有患者。我们根据机构参考范围定义正常促甲状腺激素（TSH）和游离甲状腺素（FT 4）水平。我们使用结合实验室和治疗的既定标准定义临床甲状腺功能障碍。我们使用Kaplan-Meier曲线、对数秩检验和多变量考克斯比例风险模型确定甲状腺功能与总生存期（OS）之间的关系。共有1781例患者纳入分析，其中381例（21%）基线TSH异常。基线TSH异常的患者更可能是女性，患有肾癌，并且在ICI开始后开始使用左旋甲状腺素（所有P < 0.001）。基线TSH异常的患者OS较低（中位数16 vs 27个月; P < 0.001）。在基线TSH正常的患者中，ICI开始后TSH异常的患者OS改善（中位数41 vs 22个月; P < 0.001）。在多变量考克斯模型中，基线TSH异常与OS恶化相关（HR 1.62; 95% CI，1.30-2.02; P < 0.001），而在ICI开始后开始左旋甲状腺素治疗与OS改善相关（HR 0.62; 95% CI，0.44-0.88; P = 0.008）。ICI诱导的甲状腺功能障碍与生存率提高相关，尽管ICI开始前TSH异常与生存率降低相关。甲状腺异常在一般人群中常见，并作为免疫治疗毒性。我们发现，免疫治疗诱导的甲状腺功能障碍与更好的生存率相关，但预先存在的甲状腺异常传达更差的结果。在线版本包含补充材料，可通过10.1007/s 00262 -022-03151-2获得。
Thyroid dysfunction is among the most common autoimmune diseases and immune checkpoint inhibitor (ICI)-induced immune-related adverse events (irAE). We determined the association between longitudinal thyroid function and clinical outcomes in patients treated with ICI. We identified all patients treated with ICI at UT Southwestern Medical Center from January 1, 2011, through December 31, 2020. We defined normal thyroid stimulating hormone (TSH) and free thyroxine (FT4) levels according to institutional reference range. We defined clinical thyroid dysfunction using established criteria incorporating labs and treatment. We determined the association between thyroid function and overall survival (OS) using Kaplan–Meier curves, log-rank tests, and multivariate Cox proportional hazards model. A total of 1781 patients were included in analyses, of whom 381 (21%) had abnormal baseline TSH. Patients with abnormal baseline TSH were more likely to be female, have kidney cancer, and initiate levothyroxine after ICI initiation (all P < 0.001). Patients with abnormal baseline TSH had inferior OS (median 16 vs 27 months; P < 0.001). Among patients with normal baseline TSH, those who had abnormal TSH after ICI initiation had improved OS (median 41 vs 22 months; P < 0.001). In a multivariate Cox model, abnormal baseline TSH was associated with worse OS (HR 1.62; 95% CI, 1.30–2.02; P < 0.001), while initiation of levothyroxine after ICI initiation was associated with improved OS (HR 0.62; 95% CI, 0.44–0.88; P = 0.008). ICI-induced thyroid dysfunction is associated with improved survival, although abnormal TSH prior to ICI initiation is associated with inferior survival. Thyroid abnormalities occur commonly in the general population and as immunotherapy toxicities. We found that immunotherapy-induced thyroid dysfunction is associated with better survival, but pre-existing thyroid abnormalities convey worse outcomes. The online version contains supplementary material available at 10.1007/s00262-022-03151-2.
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影响因子：
5.4
作者：
Brilli L;Danielli R;Campanile M;Secchi C;Ciuoli C;Calabrò L;Pilli T;Cartocci A;Pacini F;Di Giacomo AM;Castagna MG
通讯作者：
Castagna MG
影响因子：
4.7
作者：
Biondi, Bernadette;Bartalena, Luigi;Kahaly, George J.
通讯作者：
Kahaly, George J.
影响因子：
50.5
作者：
Menzies, A. M.;Johnson, D. B.;Long, G. V.
通讯作者：
Long, G. V.
DOI：
10.1016/s0140-6736(17)30703-1
发表时间：
2017-09-23
期刊：
Lancet (London, England)
影响因子：
--
作者：
Chaker L;Bianco AC;Jonklaas J;Peeters RP
通讯作者：
Peeters RP
影响因子：
5.8
作者：
Kim, Tae Hyuk;Kim, Kyung Won;Park, Young Joo
通讯作者：
Park, Young Joo