Farina Kyle A, Kane Michael P
1091Albany College of Pharmacy and Health Sciences, Albany, NY, USA.
Department of Pharmacy Practice, 1091Albany College of Pharmacy and Health Sciences, Albany, NY, USA.
J Pharm Pract. 2021 Feb;34(1):133-140. doi: 10.1177/0897190019850929. Epub 2019 Jul 3.
Two Food and Drug Administration-approved programmed cell death-1 (PD-1) inhibitors, nivolumab (Opdivo®), and pembrolizumab (Keytruda®), are indicated for treatment-resistant malignancies. Inhibition of PD-1 also inhibits T-cell peripheral tolerance, enhancing autoimmunity. Various autoimmune conditions have been reported with the use of these agents, including type 1 diabetes mellitus (T1DM). This article reviews literature regarding the development of T1DM in patients treated with PD-1 inhibitors and identifies strategies for the appropriate identification, monitoring, and follow-up of these patients. Published cases of T1DM related to PD-1 inhibitor therapy were identified using PubMed. Eighty-three identified publications were reviewed, of which 37 publications involving 42 cases of anti-PD-1 therapy-induced T1DM were identified. The average age of patients at presentation was 62 years and 59.5% were male. The mean number of PD-1 inhibitor doses received was 5, with a mean time to presentation of 11 weeks. Initial presentation of diabetic ketoacidosis was reported in 69% of cases, with an average blood glucose of 660 mg/dL and an average HbA of 8.7%. The exact mechanism PD-1 inhibitor therapy-induced T1DM is unknown. Blood glucose monitoring is recommended for all patients receiving anti-PD-1 therapy. Further research is needed to delineate the frequency of this adverse effect, as well as to evaluate potential risk factors and ideal management strategies.
两种经美国食品药品监督管理局批准的程序性细胞死亡蛋白1（PD-1）抑制剂，纳武单抗（欧狄沃®）和帕博利珠单抗（可瑞达®），被用于治疗难治性恶性肿瘤。抑制PD-1也会抑制T细胞外周耐受，增强自身免疫。使用这些药物已报告了各种自身免疫性疾病，包括1型糖尿病（T1DM）。本文综述了关于接受PD-1抑制剂治疗的患者发生T1DM的文献，并确定了对这些患者进行适当识别、监测和随访的策略。通过PubMed检索已发表的与PD-1抑制剂治疗相关的T1DM病例。对检索到的83篇出版物进行了综述，其中37篇出版物涉及42例抗PD-1治疗诱导的T1DM病例。患者出现症状时的平均年龄为62岁，59.5%为男性。接受PD-1抑制剂的平均剂量为5剂，出现症状的平均时间为11周。69%的病例报告最初表现为糖尿病酮症酸中毒，平均血糖为660mg/dL，平均糖化血红蛋白为8.7%。PD-1抑制剂治疗诱导T1DM的确切机制尚不清楚。建议对所有接受抗PD-1治疗的患者进行血糖监测。需要进一步研究来确定这种不良反应的发生率，以及评估潜在的风险因素和理想的管理策略。
