在基线时 TgAb 和 TPOAb 阳性模式分层的 PD-1 阻断的甲状腺功能障碍风险。
Risk of Thyroid Dysfunction in PD-1 Blockade Is Stratified by the Pattern of TgAb and TPOAb Positivity at Baseline.
机构信息
Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine, Showa-ku, Nagoya 466-8550, Japan.
Center for Advanced Medicine and Clinical Research, Nagoya University Hospital, Showa-ku, Nagoya 466-8550, Japan.
出版信息
J Clin Endocrinol Metab. 2023 Sep 18;108(10):e1056-e1062. doi: 10.1210/clinem/dgad231.
CONTEXT
Positive antithyroglobulin (TgAb) and/or antithyroid peroxidase antibodies (TPOAb) at baseline indicate a high risk of thyroid immune-related adverse events (irAEs) induced by antiprogrammed cell death-1 antibodies (anti-PD-1-Ab). However, whether the positivity patterns of both antibodies are associated with the risk of thyroid irAEs is unknown.
OBJECTIVE
The aim of the present study was to clarify the association of the pattern of TgAb and TPOAb positivity at baseline with the risk of thyroid irAEs induced by anti-PD-1-Ab.
METHODS
Patients (n = 516) were evaluated for TgAb and TPOAb at baseline and prospectively for thyroid function every 6 weeks for 24 weeks after initiating anti-PD-1-Ab.
RESULTS
Fifty-one (9.9%) patients developed thyroid irAEs (thyrotoxicosis in 34, hypothyroidism without prior thyrotoxicosis in 17). Twenty-five patients subsequently developed hypothyroidism following thyrotoxicosis. The cumulative incidence of thyroid irAEs differed among 4 groups classified by the presence of TgAb/TPOAb at baseline (group 1: TgAb-(-)/TPOAb-(-), 4.6% [19/415]; group 2: TgAb-(-)/TPOAb-(+), 15.8% [9/57]; group 3: TgAb-(+)/TPOAb-(-), 42.1% [8/19]; group 4: TgAb-(+)/TPOAb-(+), 60.0% [15/25]) as follows: groups 1 vs 2-4 (P ≤ .001) and groups 2 vs 3 (P = .008) and 4 (P < .001). There were different incidences of thyrotoxicosis (groups 1-4, 3.1%, 5.3%, 31.6%, 48.0%, respectively; P < .001) in groups 1 vs 3 and 4, and groups 2 vs 3 and 4, and of hypothyroidism (groups 1-4: 2.9%, 15.8%, 31.6%, 60.0%, respectively; P < .001) in groups 1 vs 2 to 4, and groups 2 vs 4.
CONCLUSION
The risk of thyroid irAEs was affected by the pattern of TgAb and TPOAb positivity at baseline; there were high risks of thyrotoxicosis in patients with TgAb-(+) and of hypothyroidism in patients with TgAb-(+) and those with TPOAb-(+).
背景
基线时阳性的抗甲状腺球蛋白（TgAb）和/或抗甲状腺过氧化物酶抗体（TPOAb）提示抗程序性细胞死亡-1 抗体（抗 PD-1-Ab）引起的甲状腺免疫相关不良事件（irAE）风险较高。然而，这两种抗体的阳性模式是否与甲状腺 irAE 的风险相关尚不清楚。
目的
本研究旨在阐明基线时 TgAb 和 TPOAb 阳性模式与抗 PD-1-Ab 诱导的甲状腺 irAE 风险之间的关系。
方法
对 516 例患者进行 TgAb 和 TPOAb 基线评估，并在开始抗 PD-1-Ab 后每 6 周进行 24 周的甲状腺功能前瞻性评估。
结果
51 例（9.9%）患者发生甲状腺 irAE（甲状腺毒症 34 例，甲状腺毒症后发生甲状腺功能减退 17 例）。25 例患者在甲状腺毒症后出现甲状腺功能减退。4 组根据基线时 TgAb/TPOAb 存在情况进行分组（第 1 组：TgAb（-）/TPOAb（-），4.6%[19/415]；第 2 组：TgAb（-）/TPOAb（+），15.8%[9/57]；第 3 组：TgAb（+）/TPOAb（-），42.1%[8/19]；第 4 组：TgAb（+）/TPOAb（+），60.0%[15/25]），甲状腺 irAE 的累积发生率不同：第 1 组与第 2-4 组（P ≤.001）和第 2 组与第 3 组（P =.008）和第 4 组（P <.001）。第 1 组与第 3 组和第 4 组相比，甲状腺毒症的发生率不同（第 1-4 组，分别为 3.1%、5.3%、31.6%、48.0%；P <.001），第 2 组与第 3 组和第 4 组相比，甲状腺毒症的发生率也不同（第 2-4 组，分别为 5.3%、15.8%、31.6%、48.0%；P <.001）。第 1 组与第 2 组至第 4 组相比，甲状腺功能减退的发生率不同（第 1-4 组：分别为 2.9%、15.8%、31.6%、60.0%；P <.001），第 2 组与第 4 组相比也是如此。
结论
甲状腺 irAE 的风险受基线时 TgAb 和 TPOAb 阳性模式的影响；TgAb（+）患者发生甲状腺毒症的风险较高，而 TgAb（+）和 TPOAb（+）患者发生甲状腺功能减退的风险较高。
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