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Abstract：
BACKGROUND: Anti-programmed cell death-1 (ligand-1) antibody [PD-(L)1-Ab] can cause destructive thyroiditis and/or hypothyroidism. In addition, tyrosine kinase inhibitors (TKIs) frequently induce hypothyroidism. The aim of this prospective study is to examine the incidence and clinical characteristics of thyroid dysfunction induced by combination therapy of a PD-(L)1-Ab and TKI [PD-(L)1-Ab/TKI].
METHODS: A total of 757 patients treated with PD-(L)1-Ab or PD-(L)1-Ab/TKI were evaluated for anti-thyroid antibodies (ATAs) at baseline and for thyroid function for 48 weeks after treatment initiation and then observed until the last visit.
RESULTS: The cumulative incidences of destructive thyroiditis [4/23 (17.4%) vs. 45/734 (6.1%) patients, p < 0.001], isolated hypothyroidism [10/23 (43.5%) vs. 29/734 (4.0%) patients, p < 0.001], and all thyroid dysfunction [14/23 (60.9%) vs. 74/734 (10.1%) patients, p < 0.001] were significantly higher in the PD-(L)1-Ab/TKI group than PD-(L)1-Ab group, respectively. All patients positive for ATAs at baseline developed thyroid dysfunction after PD-(L)1-Ab/TKI treatment, a significantly higher incidence than that in those negative for ATAs at baseline [4/4 (100%) vs. 10/19 (52.6%) patients, p = 0.026].
CONCLUSIONS: The addition of TKIs increased the risk of thyroid dysfunction induced by PD-(L)1-Ab, with the risk being higher in patients positive for baseline ATAs.
METHODS: A total of 757 patients treated with PD-(L)1-Ab or PD-(L)1-Ab/TKI were evaluated for anti-thyroid antibodies (ATAs) at baseline and for thyroid function for 48 weeks after treatment initiation and then observed until the last visit.
RESULTS: The cumulative incidences of destructive thyroiditis [4/23 (17.4%) vs. 45/734 (6.1%) patients, p < 0.001], isolated hypothyroidism [10/23 (43.5%) vs. 29/734 (4.0%) patients, p < 0.001], and all thyroid dysfunction [14/23 (60.9%) vs. 74/734 (10.1%) patients, p < 0.001] were significantly higher in the PD-(L)1-Ab/TKI group than PD-(L)1-Ab group, respectively. All patients positive for ATAs at baseline developed thyroid dysfunction after PD-(L)1-Ab/TKI treatment, a significantly higher incidence than that in those negative for ATAs at baseline [4/4 (100%) vs. 10/19 (52.6%) patients, p = 0.026].
CONCLUSIONS: The addition of TKIs increased the risk of thyroid dysfunction induced by PD-(L)1-Ab, with the risk being higher in patients positive for baseline ATAs.
摘要：
背景：抗程序性细胞死亡-1（配体-1）抗体[PD-（L）1-Ab]可引起破坏性甲状腺炎和/或甲状腺功能减退。此外,酪氨酸激酶抑制剂（TKIs）经常引起甲状腺功能减退。这项前瞻性研究的目的是研究PD-（L）1-Ab和TKI[PD-（L）1-Ab/TKI]联合治疗引起的甲状腺功能障碍的发生率和临床特征。
方法：总共757例接受PD-（L）1-Ab或PD-（L）1-Ab/TKI治疗的患者在基线时评估抗甲状腺抗体（ATAs），并在治疗开始后48周评估甲状腺功能，然后观察直至最后一次就诊。
结果：破坏性甲状腺炎的累积发病率[4/23（17.4%）与45/734（6.1％）患者，p<0.001],孤立性甲状腺功能减退症[10/23（43.5%）vs.29/734（4.0%）患者，p<0.001],和所有甲状腺功能障碍[14/23（60.9%）vs.74/734（10.1％）患者，p<0.001]在PD-(L)1-Ab/TKI组中显著高于PD-(L)1-Ab组,分别。基线时ATAs阳性的所有患者在PD-（L）1-Ab/TKI治疗后出现甲状腺功能障碍，在基线时，发病率明显高于ATAs阴性者[4/4（100％）与10/19（52.6%）患者，p=0.026]。
结论：添加TKI会增加PD-（L）1-Ab引起的甲状腺功能障碍的风险，基线ATAs阳性患者的风险更高。
方法：总共757例接受PD-（L）1-Ab或PD-（L）1-Ab/TKI治疗的患者在基线时评估抗甲状腺抗体（ATAs），并在治疗开始后48周评估甲状腺功能，然后观察直至最后一次就诊。
结果：破坏性甲状腺炎的累积发病率[4/23（17.4%）与45/734（6.1％）患者，p<0.001],孤立性甲状腺功能减退症[10/23（43.5%）vs.29/734（4.0%）患者，p<0.001],和所有甲状腺功能障碍[14/23（60.9%）vs.74/734（10.1％）患者，p<0.001]在PD-(L)1-Ab/TKI组中显著高于PD-(L)1-Ab组,分别。基线时ATAs阳性的所有患者在PD-（L）1-Ab/TKI治疗后出现甲状腺功能障碍，在基线时，发病率明显高于ATAs阴性者[4/4（100％）与10/19（52.6%）患者，p=0.026]。
结论：添加TKI会增加PD-（L）1-Ab引起的甲状腺功能障碍的风险，基线ATAs阳性患者的风险更高。
