Medicine, Scripps Health, La Jolla, California, USA.
Scripps Research Translational Institute, La Jolla, California, USA.
J Immunother Cancer. 2024 Jan 31;12(1):e008233. doi: 10.1136/jitc-2023-008233.
Despite immunization, patients on antineoplastic and immunomodulating agents have a heightened risk of COVID-19 infection. However, accurately attributing this risk to specific medications remains challenging.
An observational cohort study from December 11, 2020 to September 22, 2022, within a large healthcare system in San Diego, California, USA was designed to identify medications associated with greatest risk of postimmunization SARS-CoV-2 infection. Adults prescribed WHO Anatomical Therapeutic Chemical (ATC) classified antineoplastic and immunomodulating medications were matched (by age, sex, race, and number of immunizations) with control patients not prescribed these medications yielding a population of 26 724 patients for analysis. From this population, 218 blood samples were collected from an enrolled subset to assess serological response and cytokine profile in relation to immunization.
Prescription of WHO ATC classified antineoplastic and immunomodulatory agents was associated with elevated postimmunization SARS-CoV-2 infection risk (HR 1.50, 95% CI 1.38 to 1.63). While multiple immunization doses demonstrated a decreased association with postimmunization SARS-CoV-2 infection risk, antineoplastic and immunomodulatory treated patients with four doses remained at heightened risk (HR 1.23, 95% CI 1.06 to 1.43). Risk variation was identified among medication subclasses, with PD-1/PD-L1 inhibiting monoclonal antibodies, calcineurin inhibitors, and CD20 monoclonal antibody inhibitors identified to associate with increased risk of postimmunization SARS-CoV-2 infection. Antineoplastic and immunomodulatory treated patients also displayed a reduced IgG antibody response to SARS-CoV-2 epitopes alongside a unique serum cytokine profile.
Antineoplastic and immunomodulating medications associate with an elevated risk of postimmunization SARS-CoV-2 infection in a drug-specific manner. This comprehensive, unbiased analysis of all WHO ATC classified antineoplastic and immunomodulating medications identifies medications associated with greatest risk. These findings are crucial in guiding and refining vaccination strategies for patients prescribed these treatments, ensuring optimized protection for this susceptible population in future COVID-19 variant surges and potentially for other RNA immunization targets.
尽管进行了免疫接种，接受抗肿瘤和免疫调节药物治疗的患者仍有较高的 COVID-19 感染风险。然而，准确地将这种风险归因于特定的药物仍然具有挑战性。
本研究在美国加利福尼亚州圣地亚哥的一个大型医疗保健系统中，于 2020 年 12 月 11 日至 2022 年 9 月 22 日开展了一项观察性队列研究，旨在确定与接种后 SARS-CoV-2 感染风险最大相关的药物。将接受世界卫生组织（WHO）解剖治疗化学（ATC）分类的抗肿瘤和免疫调节药物治疗的成年人与未接受这些药物治疗的对照患者进行匹配（按年龄、性别、种族和免疫接种次数进行匹配），从而产生了 26724 名患者进行分析。在这一人群中，从登记的亚组中采集了 218 份血样，以评估免疫接种与血清学反应和细胞因子谱的关系。
处方 WHO ATC 分类的抗肿瘤和免疫调节药物与接种后 SARS-CoV-2 感染风险增加相关（HR 1.50，95%CI 1.38 至 1.63）。虽然多次免疫接种剂量与接种后 SARS-CoV-2 感染风险的相关性降低，但接受四剂抗肿瘤和免疫调节药物治疗的患者仍处于高风险状态（HR 1.23，95%CI 1.06 至 1.43）。药物亚类之间存在风险差异，PD-1/PD-L1 抑制单克隆抗体、钙调神经磷酸酶抑制剂和 CD20 单克隆抗体抑制剂与接种后 SARS-CoV-2 感染风险增加相关。接受抗肿瘤和免疫调节治疗的患者对 SARS-CoV-2 表位的 IgG 抗体反应也减弱，同时表现出独特的血清细胞因子谱。
抗肿瘤和免疫调节药物以药物特异性方式与接种后 SARS-CoV-2 感染风险增加相关。这项对所有 WHO ATC 分类的抗肿瘤和免疫调节药物进行的全面、无偏分析确定了与最大风险相关的药物。这些发现对于指导和完善这些治疗患者的疫苗接种策略至关重要，确保在未来 COVID-19 变异浪潮中为这一易感人群提供最佳保护，并可能为其他 RNA 免疫接种目标提供最佳保护。
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