Garon-Czmil Julie, Petitpain Nadine, Rouby Franck, Sassier Marion, Babai Samy, Yelehe-Okouma Melissa, Weryha Georges, Klein Marc, Gillet Pierre
Department of Clinical Pharmacology and Pharmacovigilance, University Hospital of Nancy, 29 avenue du Maréchal de Lattre de Tassigny, Nancy, 54035, France.
Department of Endocrinology and Medical Gynecology, University Hospital of Nancy, Rue du Morvan, Vandœuvre-lès-Nancy, 54500, France.
Fundam Clin Pharmacol. 2019 Apr;33(2):241-249. doi: 10.1111/fcp.12423. Epub 2018 Nov 14.
Immunotherapy with immune checkpoint inhibitors (ICIs) for cancer has become increasingly prescribed in recent years. Indeed, it is used to treat both solid and hematological malignancies due to their considerable potential in treating melanoma, non-small cell lung and other cancers. Immune-mediated related adverse endocrine toxicity, and especially thyroiditis, is seen as a growing problem needing specific screening and management. This study aims at describing thyroid dysfunctions induced by the ICIs marketed in France, which are registered in the French Pharmacovigilance database. This database was queried for nivolumab, pembrolizumab, and ipilimumab-induced adverse drug reactions reported before April 30, 2017. Both a pharmacologist and an endocrinologist have reviewed each case to select only those of peripheral thyroiditis (thyrotoxicosis and hypothyroidism). During this period, 110 thyroiditis following ICI therapy were reported. Sex/ratio was around one. Most of the cases (47.2%) were asymptomatic. Although some thyrotoxicosis cases were severe, no orbitopathy was reported. Hypothyroidism and thyrotoxicosis were equally described. Antithyroid antibodies were positive in only 16% patients. The ultrasonography was informative in 19% patients. Levothyroxine supplementation was necessary in 57% patients, leading to 19% recovery. With a dedicated optimized management, most of the cases did not require immunotherapy discontinuation. Finally, immune-mediated related thyroiditis is increasing due to a wider prescription of ICI therapy in various cancer conditions and systematic screening. Often asymptomatic, they lead to a local activation accompanied by hormonal deficiency in the long run. It is necessary to carry out an early and sustained multidisciplinary screening to allow immunotherapy continuation.
近年来，使用免疫检查点抑制剂（ICI）进行癌症免疫治疗的处方越来越多。事实上，由于其在治疗黑色素瘤、非小细胞肺癌和其他癌症方面具有巨大潜力，它被用于治疗实体瘤和血液系统恶性肿瘤。免疫介导的相关内分泌毒性，尤其是甲状腺炎，被视为一个日益严重的问题，需要进行特定的筛查和管理。本研究旨在描述在法国上市并登记在法国药物警戒数据库中的ICI所诱发的甲状腺功能障碍。查询该数据库中2017年4月30日前报告的纳武单抗、帕博利珠单抗和伊匹单抗引起的药物不良反应。一名药理学家和一名内分泌学家对每个病例进行了审查，仅选择外周甲状腺炎（甲状腺毒症和甲状腺功能减退）的病例。在此期间，报告了110例ICI治疗后的甲状腺炎。性别比约为1。大多数病例（47.2%）无症状。虽然一些甲状腺毒症病例很严重，但未报告眼眶病。甲状腺功能减退和甲状腺毒症的描述相同。仅16%的患者抗甲状腺抗体呈阳性。19%的患者超声检查有诊断价值。57%的患者需要补充左甲状腺素，其中19%恢复。通过专门优化的管理，大多数病例不需要停止免疫治疗。最后，由于ICI治疗在各种癌症情况下的处方范围扩大和系统筛查，免疫介导的相关甲状腺炎正在增加。它们通常无症状，最终会导致局部激活并伴有激素缺乏。有必要进行早期和持续的多学科筛查，以允许继续进行免疫治疗。
