Boulefaa Dalil, Bagheri Haleh, Salvo Francesco, Rabier Marie-Blanche, Geniaux Hélène, Lepelley Marion, Rocher Fanny, Mahe Julien, Grandvillemuin Aurélie, Thai-Van Hung
Department of Medical and Clinical Pharmacology, Regional Pharmacovigilance Centre of Toulouse, Clinical Investigation Centre 1436, Toulouse University Hospital, Toulouse, France.
Department of Medical Pharmacology, Hospital University of Bordeaux, Inserm, BPH, U1219, Equipe AHeaD, Bordeaux, France.
Drug Saf. 2025 Mar;48(3):251-263. doi: 10.1007/s40264-024-01495-5. Epub 2024 Dec 5.
Improving adverse events following immunisation (AEFI) detection is vital for vaccine safety surveillance, as an early safety signal can help minimize risks. In February 2022, the World Health Organization reported a preliminary signal on sudden sensorineural hearing loss (SSNHL) following coronavirus disease 2019 (COVID-19) vaccination, 54 million persons in France received at least one dose, covering 78.8% of the population within a year.
The primary objective of this study was to identify a method of disproportionality analysis capable to detect a safety signal for hearing impairment (HI) as early as possible during the initial phases of the COVID-19 vaccination campaign. Secondly, we described all cases of SSNHL reported during vaccine booster campaigns in France.
Data from January 2011 to February 2022 were extracted from the French pharmacovigilance database. Cases were all spontaneous reports of AEFI for elasomeran and tozinameran, while non-cases were AEFI reported for other vaccines. Disproportionality analysis for HI was performed monthly during 2021, to estimate a reporting odds ratio (ROR). Four different methods were used for ROR estimation. Furthermore, we reviewed cases of SSNHL following messenger RNA COVID-19 vaccinations reported during booster campaigns, from 2 February 2022 to 1 March 2023, based on a comprehensive medical evaluation.
Using a standard methodology, we identified a signal on 31 July 2021 (ROR 1.50, 95% confidence interval [CI] [1.06-2.18]). Multivariate analysis adjusted for sex, age, ototoxic drugs and excluding reference reports of common AEFI for vaccines allowed us to detect the HI signal as early as 31 March 2021 (ROR 2.67, 95% CI [1.36-5.57]). The SSNHL reporting rate was estimated to be 0.83/1,000,000 doses for tozinameran and 4.3/1,000,000 for elasomeran during the booster campaigns.
Using a well-structured disproportionality analysis could have enhanced early detection of safety signals and contribute to risk minimizing measures. According to descriptive data, HI following mRNA COVID-19 vaccines remains rare.
改善免疫接种后不良事件（AEFI）的监测对于疫苗安全监测至关重要，因为早期安全信号有助于将风险降至最低。2022年2月，世界卫生组织报告了2019冠状病毒病（COVID-19）疫苗接种后突发感音神经性听力损失（SSNHL）的初步信号。在法国，有5400万人接种了至少一剂疫苗，一年内覆盖了78.8%的人口。
本研究的主要目的是确定一种不成比例分析方法，能够在COVID-19疫苗接种活动的初始阶段尽早检测出听力障碍（HI）的安全信号。其次，我们描述了法国疫苗加强接种活动期间报告的所有SSNHL病例。
从法国药物警戒数据库中提取2011年1月至2022年2月的数据。病例均为关于弹性体佐剂和托珠单抗的AEFI自发报告，而非病例为其他疫苗的AEFI报告。2021年每月对HI进行不成比例分析，以估计报告比值比（ROR）。使用四种不同方法估计ROR。此外，我们基于全面的医学评估，回顾了2022年2月2日至2023年3月1日加强接种活动期间报告的mRNA COVID-19疫苗接种后SSNHL病例。
采用标准方法，我们于2021年7月31日发现了一个信号（ROR 1.50，95%置信区间[CI][1.06 - 2.18]）。针对性别、年龄、耳毒性药物进行多变量分析，并排除疫苗常见AEFI的参考报告后，我们最早于2021年3月31日检测到HI信号（ROR 2.67，95% CI [1.36 - 5.57]）。在加强接种活动期间，托珠单抗的SSNHL报告率估计为0.83/100万剂，弹性体佐剂为4.3/100万剂。
使用结构良好的不成比例分析可以加强安全信号的早期检测，并有助于采取风险最小化措施。根据描述性数据，mRNA COVID-19疫苗接种后的HI仍然罕见。
