Metabolic and Nutritional Disorders Following the Administration of Immune Checkpoint Inhibitors: A Pharmacovigilance Study

Frontiers in Endocrinology

Endocrinology

Yang Cao¹  Jinfang Xu²  Yi Zheng²  Xiaofei Ye²  Xiaojing Guo²  Fangyuan Hu³  Yinghong Zhai⁴  Xiang Zhou⁴  Xinxin Zhao⁴  Xiao Xu⁴  Jia He⁵ 

[1] Clinical Epidemiology and Biostatistics, School of Medical Sciences, Örebro University, Örebro, Sweden;Unit of Integrative Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden;Department of Health Statistics, Second Military Medical University, Shanghai, China;Department of Health Statistics, Second Military Medical University, Shanghai, China;Department of Medical Service, Naval Hospital of Eastern Theater Zhoushan, Zhejiang, China;Tongji University School of Medicine, Shanghai, China;Tongji University School of Medicine, Shanghai, China;Department of Health Statistics, Second Military Medical University, Shanghai, China;

关键词: metabolic and nutritional disorders;    immune checkpoint inhibitors;    FAERS database;    pharmacovigilance study;    disproportionality analysis;    reporting odds ratio;    information component;   

DOI  :  10.3389/fendo.2021.809063

 received in 2021-11-04, accepted in 2021-12-28,  发布年份 2022

来源: Frontiers

【 摘 要 】

BackgroundAlthough several metabolic and nutritional disorders (MNDs) have been reported in the recipients of immune checkpoint inhibitors (ICIs), these events have not been fully captured and comprehensively characterized in real-world population.ObjectivesTo provide complete metabolic and nutritional toxicity profiles after ICIs (single and combined) initiation through an integrated big database.MethodsReporting odds ratios (ROR) and information component (IC) based on statistical shrinkage transformation were utilized to perform disproportionality analysis using the US Food and Drug Administration Adverse Events Reporting System. Both ROR and IC were used to calculate disproportionality when compared with the whole database, but only ROR was used when comparison was made for different ICI strategies. Only when both the lower limits of 95% confidence intervals (CIs) for ROR (ROR025) and IC (IC025) exceeded specified threshold values (1 and 0, respectively) was regarded as a signal.ResultsA total of 29,294,335 records were involved and 8,662 records were for MNDs in patients exposed to ICIs. Statistically significant association was detected between ICIs use and total MNDs (IC025/ROR025 = 1.06/2.19). For monotherapy, three ICI monotherapies (anti-PD-1, anti-PDL-1, and anti-CTLA-4) were all disproportionately associated with MNDs. Statistically significant differences in reporting frequencies also emerged when comparing anti-PD-1 with anti-PD-L1/anti-CTLA-4 monotherapy, with RORs of 1.11 (95%CI 1.01-1.21), and 1.35 (95%CI 1.23-1.48), respectively. Notably, combination therapy was associated with a higher reporting frequency of theses toxicities compared to monotherapy with a ROR of 1.56 (95%CI 1.48-1.64). Additionally, disproportionality analysis at High-level Group Term level highlighted eight broad entities of MNDs. Further disproportionality analysis at Preferred Term level indicated a wide range and varied strength of signals. For ICI monotherapy, nivolumab and pembrolizumab showed the broadest spectrum of MNDs. For combination therapy, a variety of signals were detected for nivolumab + ipilimumab therapy even comparable to two PD-1 monotherapies.ConclusionMetabolic and nutritional complications could be provoked by ICI monotherapy (especially anti-PD-1) and further reinforced by combination therapy. Clinicians and patients should be informed about these potential risks that might be encountered in real-world practice. Aforehand education and regular monitoring of related biochemical parameters (calcium, sodium, potassium, protein) are recommended to ensure better cancer survivorship.

【 授权许可】

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Copyright © 2022 Zhai, Ye, Hu, Xu, Guo, Zhou, Zheng, Zhao, Xu, Cao and He