接种疫苗后出现的不良事件——中性粒细胞减少症：健康成年人随机临床试验结果及系统评价

Neutropenia as an Adverse Event following Vaccination: Results from Randomized Clinical Trials in Healthy Adults and Systematic Review.

作者信息

Muturi-Kioi Vincent, Lewis David, Launay Odile, Leroux-Roels Geert, Anemona Alessandra, Loulergue Pierre, Bodinham Caroline L, Aerssens Annelies, Groth Nicola, Saul Allan, Podda Audino

机构信息

Novartis Vaccines Institute for Global Health, Siena, Italy.

Surrey Clinical Research Centre, University of Surrey, Guildford, United Kingdom.

出版信息

PLoS One. 2016 Aug 4;11(8):e0157385. doi: 10.1371/journal.pone.0157385. eCollection 2016.

DOI:10.1371/journal.pone.0157385

PMID:27490698

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4974007/

Abstract

BACKGROUND

In the context of early vaccine trials aimed at evaluating the safety profile of novel vaccines, abnormal haematological values, such as neutropenia, are often reported. It is therefore important to evaluate how these trials should be planned not to miss potentially important safety signals, but also to understand the implications and the clinical relevance.

METHODOLOGY

We report and discuss the results from five clinical trials (two with a new Shigella vaccine in the early stage of clinical development and three with licensed vaccines) where the absolute neutrophil counts (ANC) were evaluated before and after vaccination. Additionally, we have performed a systematic review of the literature on cases of neutropenia reported during vaccine trials to discuss our results in a more general context.

PRINCIPAL FINDINGS

Both in our clinical trials and in the literature review, several cases of neutropenia have been reported, in the first two weeks after vaccination. However, neutropenia was generally transient and had a benign clinical outcome, after vaccination with either multiple novel candidates or well-known licensed vaccines. Additionally, the vaccine recipients with neutropenia frequently had lower baseline ANC than non-neutropenic vaccinees. In many instances neutropenia occurred in subjects of African descent, known to have lower ANC compared to western populations.

CONCLUSIONS

It is important to include ANC and other haematological tests in early vaccine trials to identify potential safety signals. Post-vaccination neutropenia is not uncommon, generally transient and clinically benign, but many vaccine trials do not have a sampling schedule that allows its detection. Given ethnic variability in the level of circulating neutrophils, normal ranges taking into account ethnicity should be used for determination of trial inclusion/exclusion criteria and classification of neutropenia related adverse events.

TRIAL REGISTRATION

ClinicalTrials.gov NCT02017899, NCT02034500, NCT01771367, NCT01765413, NCT02523287.

摘要

背景

在旨在评估新型疫苗安全性的早期疫苗试验中，经常报告血液学异常值，如中性粒细胞减少症。因此，重要的是评估这些试验应如何规划，既不能错过潜在的重要安全信号，又要理解其影响和临床相关性。

方法

我们报告并讨论了五项临床试验（两项针对处于临床开发早期的新型志贺氏菌疫苗，三项针对已获许可的疫苗）的结果，这些试验在接种疫苗前后评估了绝对中性粒细胞计数（ANC）。此外，我们对疫苗试验期间报告的中性粒细胞减少症病例的文献进行了系统综述，以便在更广泛的背景下讨论我们的结果。

主要发现

在我们的临床试验和文献综述中，均报告了接种疫苗后前两周内出现的几例中性粒细胞减少症病例。然而，无论是接种多种新型候选疫苗还是知名的已获许可疫苗后，中性粒细胞减少症通常是短暂的，临床结局良好。此外，出现中性粒细胞减少症的疫苗接种者的基线ANC通常低于未出现中性粒细胞减少症的接种者。在许多情况下，中性粒细胞减少症发生在非洲裔受试者中，已知该人群的ANC低于西方人群。

结论

在早期疫苗试验中纳入ANC和其他血液学检查以识别潜在安全信号很重要。接种疫苗后出现的中性粒细胞减少症并不罕见，通常是短暂的且临床结局良好，但许多疫苗试验没有允许检测到它的采样计划。鉴于循环中性粒细胞水平存在种族差异，应使用考虑种族因素的正常范围来确定试验纳入/排除标准以及对与中性粒细胞减少症相关的不良事件进行分类。