Association of antithyroglobulin antibodies with the development of thyroid dysfunction induced by nivolumab.
Association of antithyroglobulin antibodies with the development of thyroid dysfunction induced by nivolumab.
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DOI：
10.1111/cas.13800
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发表时间：
2018-11
期刊：
影响因子：
5.7
通讯作者：
Ohe Y
中科院分区：
文献类型：
--
作者：
Kimbara S;Fujiwara Y;Iwama S;Ohashi K;Kuchiba A;Arima H;Yamazaki N;Kitano S;Yamamoto N;Ohe Y
免疫检查点抑制剂诱导的甲状腺功能障碍（TD）尚未充分了解。这项回顾性观察性研究的目的是确定纳武单抗引起的TD的危险因素和临床病程。纳入了2009年3月至2016年3月在国立癌症中心医院（日本东京）接受nivolumab治疗的晚期实体瘤患者。在基线和纳武单抗治疗期间评估所有患者血清样本的甲状腺功能和抗甲状腺抗体。明显的甲状腺功能减退被定义为低血清游离T4并升高促甲状腺激素（TSH） bbb10 μIU/mL。甲状腺毒症定义为低TSH伴游离T4和/或游离T3升高。我们将甲状腺自身免疫定义为基线时存在抗甲状腺抗体，包括抗甲状腺过氧化物酶抗体和抗甲状腺球蛋白抗体（TgAb）。168例患者中有23例（14%）发展为TD，包括17例甲状腺功能减退和20例甲状腺毒症。甲状腺毒症合并甲状腺功能减退14例。35名甲状腺自身免疫患者中有14名（40%）发展为TD， 133名患者中有9名（7%）未发展为TD（优势比9.19；95%可信区间[CI]， 3.53‐23.9）。在多变量分析中，基线时TSH和TgAb升高与TD的发展显著相关，比值比分别为7.36 （95% CI, 1.66‐32.7）和26.5 （95% CI, 8.18‐85.8）。TD与基线时抗甲状腺过氧化物酶抗体升高的相关性不显著。这些结果表明，先前存在TgAb和基线TSH升高的患者患TD的风险很高。
Thyroid dysfunction (TD) induced by immune checkpoint inhibitors is not sufficiently understood. The purpose of this retrospective observational study was to identify risk factors and the clinical course of TD induced by nivolumab. Patients with advanced solid tumors who were treated with nivolumab from March 2009 through to March 2016 at the National Cancer Center Hospital (Tokyo, Japan) were included. Thyroid function and antithyroid Abs from serum samples among all patients were evaluated at baseline and during nivolumab treatment. Overt hypothyroidism was defined as low serum‐free T4 together with elevated thyroid‐stimulating hormone (TSH) >10 μIU/mL. Thyrotoxicosis was defined as low TSH with elevated free T4 and/or free T3. We defined thyroid autoimmunity as the presence of antithyroid Abs at baseline, including antithyroid peroxidase Abs and antithyroglobulin Abs (TgAb). Twenty‐three (14%) of a total of 168 patients developed TD, including 17 cases of hypothyroidism and 20 of thyrotoxicosis. Thyrotoxicosis followed by hypothyroidism occurred in 14 cases. Fourteen of 35 patients (40%) with thyroid autoimmunity developed TD vs 9 of 133 (7%) without (odds ratio 9.19; 95% confidence interval [CI], 3.53‐23.9). In multivariate analysis, elevated TSH and TgAb at baseline were significantly associated with the development of TD, with odds ratio of 7.36 (95% CI, 1.66‐32.7) and 26.5 (95% CI, 8.18‐85.8), respectively. Association between TD and elevated antithyroid peroxidase Abs at baseline was not significant. These results suggest that patients with pre‐existing TgAb and elevated TSH at baseline are at high risk of TD.
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DOI：
10.1056/nejmoa1003466
发表时间：
2010-08-19
期刊：
The New England journal of medicine
影响因子：
--
作者：
Hodi FS;O'Day SJ;McDermott DF;Weber RW;Sosman JA;Haanen JB;Gonzalez R;Robert C;Schadendorf D;Hassel JC;Akerley W;van den Eertwegh AJ;Lutzky J;Lorigan P;Vaubel JM;Linette GP;Hogg D;Ottensmeier CH;Lebbé C;Peschel C;Quirt I;Clark JI;Wolchok JD;Weber JS;Tian J;Yellin MJ;Nichol GM;Hoos A;Urba WJ
通讯作者：
Urba WJ
影响因子：
5.7
作者：
Hida T;Nishio M;Nogami N;Ohe Y;Nokihara H;Sakai H;Satouchi M;Nakagawa K;Takenoyama M;Isobe H;Fujita S;Tanaka H;Minato K;Takahashi T;Maemondo M;Takeda K;Saka H;Goto K;Atagi S;Hirashima T;Sumiyoshi N;Tamura T
通讯作者：
Tamura T
影响因子：
158.5
作者：
Robert, Caroline;Schachter, Jacob;Ribas, Antoni
通讯作者：
Ribas, Antoni
DOI：
10.1056/nejmoa1510665
发表时间：
2015-11-05
期刊：
The New England journal of medicine
影响因子：
--
作者：
Motzer RJ;Escudier B;McDermott DF;George S;Hammers HJ;Srinivas S;Tykodi SS;Sosman JA;Procopio G;Plimack ER;Castellano D;Choueiri TK;Gurney H;Donskov F;Bono P;Wagstaff J;Gauler TC;Ueda T;Tomita Y;Schutz FA;Kollmannsberger C;Larkin J;Ravaud A;Simon JS;Xu LA;Waxman IM;Sharma P;CheckMate 025 Investigators
通讯作者：
CheckMate 025 Investigators
影响因子：
3.1
作者：
Kiyohara, Yoshio;Uhara, Hisashi;Yamazaki, Naoya
通讯作者：
Yamazaki, Naoya