意大利接种 COVID-19 疫苗后引发急性阑尾炎:自我控制病例系列研究

IF 4 2区 医学 Q1 PHARMACOLOGY & PHARMACY
Cristina Morciano, Marco Massari, Maria Cutillo, Valeria Belleudi, Gianluca Trifirò, Nadia Mores, Ester Sapigni, Aurora Puccini, Giovanna Zanoni, Manuel Zorzi, Giuseppe Monaco, Olivia Leoni, Stefania Del Zotto, Sarah Samez, Flavia Mayer, Giuseppe Marano, Francesca Menniti Ippolito, Roberto Da Cas, Giuseppe Traversa, Stefania Spila Alegiani
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引用次数: 0

摘要

背景和目的在 BNT162b2 mRNA 疫苗的关键随机临床试验中发现了阑尾炎病例,2019 年冠状病毒疾病(COVID-19)疫苗药物警戒系统也报告了阑尾炎病例。三项队列研究和两项自我对照病例系列 (SCCS) 研究评估了 mRNA 疫苗与阑尾炎之间的关系,但报告的结果并不一致。为了解决这一不确定性,本研究采用 SCCS 设计,在大量人群中研究了 mRNA(BNT162b2 和 mRNA-1273)和病毒载体(ChAdOx1-S 和 Ad26.COV2-S)COVID-19 疫苗与急性阑尾炎之间的关系。这项研究基于通过 TheShinISS 应用程序进行的健康档案记录链接,该应用程序是一种统计工具,可根据特定的、适合研究的通用数据模型对来自地区医疗保健数据库的数据进行本地化处理。研究对象包括 2020 年 12 月 27 日至 2021 年 9 月 30 日期间年龄≥ 12 岁的所有接种对象。急性阑尾炎通过入院或急诊就诊的出院诊断确定。病例定义为在研究期间首次患急性阑尾炎的受试者,不包括在过去 5 年中被诊断为阑尾炎的受试者。暴露定义为BNT162b2、mRNA-1273和ChAdOx1-S的第一或第二剂量以及Ad26.COV2-S的单剂量。风险间隔被定义为自第一或第二剂疫苗接种起的 42 天,并分为预先指定的风险子期;参照期为风险间隔外的观察时间。相对发病率 (RI) 和 95% 置信区间 (95% CI) 是通过无偏估计方程,采用 "针对事件依赖性暴露进行修改 "的 SCCS 方法估算的。结果 在 42 天的风险区间内,共发生了 1285 例急性阑尾炎:其中 727 例发生在第一剂后,558 例发生在第二剂后。在主要分析中,接种 BNT162b、mRNA-1273、ChAdOx1-S 和 Ad26.COV2-S 的受试者患急性阑尾炎的风险没有增加。按性别进行的亚组分析显示,男性在接种第一剂 mRNA-1273 后(RI 为 1.71;95% CI 为 1.08-2.70,p = 0.02),女性在接种一剂 Ad26.COV2-S 后(RI 为 1.71;95% CI 为 1.08-2.70,p = 0.02),在 14-27 天的风险区间内风险增加。结论在普通人群中,没有证据表明 BNT162b、ChAdOx1-S、mRNA-1273 和 Ad26.COV2-S 与急性阑尾炎有关。按性别进行的亚组分析结果需要慎重考虑。不能排除多重性问题,因为这些假设是测试的几个假设中的两个。此外,关于疾病生物学机制的相关文献以及使用其他疫苗或相同疫苗产生类似效果的证据仍然缺乏,因此无法有力地支持关于男性和女性使用 mRNA-1273 和 Ad26.COV2-S 会产生有害影响的结论。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Acute Appendicitis After COVID-19 Vaccines in Italy: A Self-Controlled Case Series Study

Acute Appendicitis After COVID-19 Vaccines in Italy: A Self-Controlled Case Series Study

Background and Objective

Cases of appendicitis were identified in the pivotal randomized clinical trial on BNT162b2 mRNA vaccine and reported from coronavirus disease 2019 (COVID-19) vaccine pharmacovigilance systems. Three cohort studies and two self-controlled case series (SCCS) studies evaluating the association between mRNA vaccines and appendicitis reported discordant results. To address this uncertainty, the present study examines in a large population, with a SCCS design, the association between mRNA (BNT162b2 and mRNA-1273) and, for the first time, viral vector (ChAdOx1-S and Ad26.COV2-S) COVID-19 vaccines and acute appendicitis.

Methods

The SCCS study design was used to evaluate the association between COVID-19 vaccination and subsequent onset of acute appendicitis. The study was based on record linkage of health archives through TheShinISS application, a statistical tool that locally processes data from regional health care databases according to ad hoc, study-tailored and common data model. The study population included all vaccinated subjects ≥ 12 years old between 27 December 2020 and 30 September 2021. The acute appendicitis was identified through discharge diagnoses of hospital admissions or emergency department visits. Incident cases were defined as those who experienced a first event of acute appendicitis in the study period, excluding subjects with a diagnosis of appendicitis in the previous 5 years. Exposure was defined as the first or second dose of BNT162b2, mRNA-1273 and ChAdOx1-S and the single dose of Ad26.COV2-S. The risk interval was defined as 42 days from the first or second vaccination dose and divided into pre-specified risk subperiods; the reference period was the observation time outside the risk interval. Relative incidences (RI) and 95% confidence intervals (95% CI) were estimated with the SCCS method ‘modified for event-dependent exposures’, through unbiased estimating equations. The seasonal component was considered as a time-dependent covariate.

Results

In the 42-day risk interval 1285 incident cases of acute appendicitis occurred: 727 cases after the first dose and 558 cases after the second dose. In the main analysis, no increased risks of acute appendicitis were observed in subjects vaccinated with BNT162b, mRNA-1273, ChAdOx1-S and Ad26.COV2-S. The subgroup analyses by sex showed an increased risk in the 14–27 day risk interval, in males after the first dose of mRNA-1273 (RI of 1.71; 95% CI 1.08–2.70, p = 0.02) and in females after the single dose of Ad26.COV2-S (RI of 4.40; 95% CI 1.29–15.01, p = 0.02).

Conclusions

There was no evidence of association of BNT162b, ChAdOx1-S, mRNA-1273 and Ad26.COV2-S with acute appendicitis in the general population. The results of the subgroup analyses by sex needs to be considered with caution. The multiplicity issue cannot be excluded being these hypotheses two of several hypotheses tested. In addition, relevant literature on the biological mechanism of the disease and evidence of similar effects with other vaccines or with the same vaccines are still lacking to provide strong support for a conclusion that there is an harmful effect in males and females with mRNA-1273 and Ad26.COV2-S.

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来源期刊
Drug Safety
Drug Safety 医学-毒理学
CiteScore
7.60
自引率
7.10%
发文量
112
审稿时长
6-12 weeks
期刊介绍: Drug Safety is the official journal of the International Society of Pharmacovigilance. The journal includes: Overviews of contentious or emerging issues. Comprehensive narrative reviews that provide an authoritative source of information on epidemiology, clinical features, prevention and management of adverse effects of individual drugs and drug classes. In-depth benefit-risk assessment of adverse effect and efficacy data for a drug in a defined therapeutic area. Systematic reviews (with or without meta-analyses) that collate empirical evidence to answer a specific research question, using explicit, systematic methods as outlined by the PRISMA statement. Original research articles reporting the results of well-designed studies in disciplines such as pharmacoepidemiology, pharmacovigilance, pharmacology and toxicology, and pharmacogenomics. Editorials and commentaries on topical issues. Additional digital features (including animated abstracts, video abstracts, slide decks, audio slides, instructional videos, infographics, podcasts and animations) can be published with articles; these are designed to increase the visibility, readership and educational value of the journal’s content. In addition, articles published in Drug Safety Drugs may be accompanied by plain language summaries to assist readers who have some knowledge of, but not in-depth expertise in, the area to understand important medical advances.
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