Department of Endocrinology, Second Affiliated Hospital of Fujian Medical University, No. 950 Donghai Street, Fengze, Quanzhou, Fujian, China.
Department of Medical Administration, Second Affiliated Hospital of Fujian Medical University, No. 950 Donghai Street, Fengze, Quanzhou, Fujian, China.
J Endocrinol Invest. 2020 Oct;43(10):1473-1483. doi: 10.1007/s40618-020-01226-4. Epub 2020 Apr 1.
The aim of this study was to identify and characterize immune checkpoint inhibitors (ICIs)-associated pituitary adverse events (AEs).
This is a retrospective disproportionality study based on VigiBase, the World Health Organization (WHO) global database of individual case safety reports (ICSRs), with a study period from January 1, 2011 to March 6, 2019. Information component (IC) and reporting odds ratio (ROR) are measures of disproportionate analysis. IC was used to evaluate the association between ICIs and pituitary AEs, while ROR was used to evaluate the differences in reporting of pituitary AEs between different ICI subgroups.
The following ICI-associated pituitary diseases have been increasingly reported: hypophysitis (835 reports; information component 6.74 [95% CI 6.63-6.83]), hypopituitarism (268; 6.12 [95% CI 5.92-6.27]), pituitary enlargement (28; 5.19 [95% CI 4.57-5.63]). The anti-CTLA-4 subgroup had a stronger association with hypophysitis/hypopituitarism than the anti-PD (anti-PD-1 or anti-PD-L1) subgroup (ROR 8.0 [95% CI 6.7-9.6]). Among ICI-associated hypophysitis/hypopituitarism cases, the proportion of male was higher than female (630 [63.9%] vs 356 [36.1%]). Anti-CTLA-4 subgroup and ICI combination (nivolumab plus ipilimumab) subgroup both had a significantly earlier onset time than anti-PD subgroup (67 days [IQR 48-87]; 90 [IQR 34-155]; 140 [IQR 62-218], both p < 0.05). Other endocrinopathies that co-occurred with hypophysitis/hypopituitarism were adrenal insufficiency, thyroid dysfunction, diabetes mellitus and diabetes insipidus. Gastrointestinal disorder was the most common concurrent disease except for endocrinopathies.
ICI-associated pituitary adverse events have significantly increased, and their clinical characteristics should be kept in mind by oncologists and endocrinologists who manage patients treated by immunotherapy.
本研究旨在识别和描述免疫检查点抑制剂（ICI）相关的垂体不良事件（AE）。
这是一项基于世界卫生组织（WHO）个体病例安全报告（ICSR）全球数据库 VigiBase 的回顾性不成比例研究，研究期间为 2011 年 1 月 1 日至 2019 年 3 月 6 日。信息成分（IC）和报告比值比（ROR）是不成比例分析的衡量指标。IC 用于评估 ICI 与垂体 AE 之间的关联，而 ROR 用于评估不同 ICI 亚组之间垂体 AE 报告的差异。
越来越多的报道表明，以下 ICI 相关的垂体疾病：垂体炎（835 例报告；IC 6.74 [95%CI 6.63-6.83]）、垂体功能减退（268 例；6.12 [95%CI 5.92-6.27]）、垂体增大（28 例；5.19 [95%CI 4.57-5.63]）。与 CTLA-4 拮抗剂相比，PD（抗 PD-1 或抗 PD-L1）拮抗剂与垂体炎/垂体功能减退的相关性更强（ROR 8.0 [95%CI 6.7-9.6]）。在 ICI 相关的垂体炎/垂体功能减退患者中，男性比例高于女性（630 例[63.9%]比 356 例[36.1%]）。CTLA-4 拮抗剂和 ICI 联合（纳武单抗联合伊匹单抗）组的发病时间明显早于 PD 拮抗剂组（67 天 [IQR 48-87]；90 天 [IQR 34-155]；140 天 [IQR 62-218]，均 P<0.05）。垂体炎/垂体功能减退同时发生的其他内分泌疾病有肾上腺皮质功能不全、甲状腺功能障碍、糖尿病和尿崩症。除内分泌疾病外，胃肠道疾病是最常见的伴发病。
ICI 相关的垂体不良事件显著增加，接受免疫治疗的患者的肿瘤学家和内分泌学家应注意其临床特征。
