ABSTRACT
Introduction: Cases of Guillain-Barré Syndrome (GBS) have been reported following numerous vaccines but the causality still remains controversial. An intensive worldwide pharmacovigilance survey for Covid-19 vaccines raised a concern about the risk of GBS with adenovirus-vectored vaccines (ChAdOx1-S and Ad26.COV2-S). The objective of this observed to expected analysis was to assess this risk using French pharmacovigilance data. Material and methods: Spontaneous reports of GBS associated with ChAdOx1-S and Ad26.COV2-S vaccines were extracted from the French Pharmacovigilance Database on 30 December 2021 and reviewed. Only cases with a level 1 or 2 of certainty for GBS using the Brighton collaboration scale were retained and occurring within 42-days after vaccination. The number of doses administered have been collected via the VACSI platform on 4 November 2021, i-e 8 weeks before case extraction to allow the diagnosis of GBS, its reporting, and its registering in the database. Results: On 4 November 2021, 7,796,068 doses of ChAdOx1-S vaccine and 1,045,576 doses of Ad26.COV2-S vaccine were administered in France. After the exclusion of 13 cases, 47 cases were included (39 with ChAdOx1-S and 8 with Ad26.COV2-S). Considering an annual incidence of GBS of 1 to 2 per 100 000 persons [1], the number of expected cases for both vaccines was 10.2 to 20.4 respectively (9 to 18 expected cases for ChAdOx1-S and 1.2 to 2.4 expected cases for Ad26.COV2-S). The O/E ratio for both vaccines was 4.6 [95%CI 3.4-6.1] and 2.3 [95%CI 1.7-3.1] respectively considering both incidences, without taking into account any under-reporting. This ratio, quite similar for ChAdOx1-S was higher with Ad26.COV2-S: between 6.6 [95%CI 2.9-13.1] and 3.3 [95%CI 1.4-6.5]. Discussion/Conclusion: This original method confirms the risk of GBS following administration of adenovirus-vectored vaccines based on French data. This signal was also confirmed by EMA.
ABSTRACT
Explain what has changed the practice: As part of the Covid-19 vaccination campaign, the ANSM and all the 31 regional pharmacovigilance centers have been mobilised in an exceptional reinforced surveillance program. The aim of this national system is not to be exhaustive nor to compare vaccines but to detect safety signals in addition to European and international pharmacovigilance actions. It is based on the daily analysis of adverse reactions cases reported in the national pharmacovigilance database by experts in charge of the surveillance of each Covid-19 vaccines. As for other Covid vaccines, the number of administered doses of Astrazeneca Covid-19 vaccine (ChAdOx1-S vaccine) has been collected via the VACSI platform and spontaneous reports were extracted from the French Pharmacovigilance Database on 12/30/2021 and reviewed. On 30/12/2021, 7 832 223 doses of ChAdOx1-S vaccine were administered in France with 28 313 notifications corresponding to 53 389 adverse events, of among which one fifth were considered serious according to WHO criteria. The first pharmacovigilance signal, which appeared after the first injections, was unexpectedly severe flulike syndromes, according to the SPC. It was quickly followed by a more serious problem that would have a major impact on the vaccination campaign at both national and European level: Immune thrombotic thrombocytopenia (ITT). Subsequently, other signals highlighted during pharmacovigilance monitoring, such as Guillain-Barré syndromes, facial paralysis, capillary leak syndromes, urticaria and angioedema, and more recently, immune thrombocytopenia and cerebral venous thrombosis all of which remind the importance of post-authorisation monitoring. All those signals were transmitted to the European authorities, some of which led to the updating of the VaxZevria SPC. Today, the AstraZeneca vaccine has only a marginal place in the national vaccination strategy, but pharmacovigilance monitoring is still ongoing.
ABSTRACT
OBJECTIVES: The primary objective of the present study was to describe the characteristics of adverse drug reactions (ADRs) linked to self-medication that were notified to the French Pharmacovigilance Database (FPVD) during the COVID-19 outbreak in 2020 first wave. The secondary objective was to compare the characteristics of these ADRs in 2020 with those notified during the same calendar period a year previously. MATERIAL AND METHODS: We analyzed ADRs recorded in the FPVD between March 15th and May 31st, 2020 vs. the same dates in 2019. Only ADRs linked to self-medication were analyzed. Descriptive statistics were used to obtain an overview of the types and characteristics of these ADRs. RESULTS: Of 3114 ADRs notified to the FPVD during the COVID-19 period in 2020, 114 (3.7%) were linked to self-medication. The equivalent proportion in 2019 was 1.6% (113 out of 7097). Half of the ADRs notified in 2020 were "serious". The median age of affected patients was 30.5, and 22% of the ADRs concerned children. Of the 114 ADRs linked to self-medication, 107 (66%) were for prescription-only drugs. The three mostly frequently suspected ATC classes were analgesics, psycholeptics, and antibacterials for systemic use. The most frequent ADRs were general disorders, gastrointestinal disorders, and nervous system disorders. The main difference between the non-COVID-19 period and the COVID-19 period was the higher proportion of medication errors during the latter. CONCLUSION: The present study is the first to have reported on ADRs linked to self-medication and notified during a COVID-19 outbreak. Further studies of self-medication patterns and their consequences in a pandemic context are mandatory and effective information on medication use (including self-medication and its dangers) during a pandemic is essential.
Subject(s)
Adverse Drug Reaction Reporting Systems , COVID-19 , Drug-Related Side Effects and Adverse Reactions/epidemiology , Pandemics , Self Medication/adverse effects , Self Report , Accidents , Adolescent , Child , Child, Preschool , Drug Overdose/epidemiology , France , Humans , Medical Errors , PharmacovigilanceABSTRACT
Introduction Les immunosuppresseurs utilisés chez les greffés et les personnes atteintes de cancer sont associés à des formes sévères de COVID-19 et à une augmentation de la mortalité. Parmi les classes de médicaments antirhumatismaux modificateurs de la maladie (DMARDs), il est largement reconnu que les médicaments biologiques sont associés à une susceptibilité de réactivation virale et de formes sévères de grippe. L’objectif de cette étude est de déterminer s’il existe une disproportionnalité de notifications des cas de COVID-19 pour certaines classes de DMARDs utilisés au cours des rhumatismes inflammatoires chroniques (RIC). Patients et méthodes Une analyse–dite de cas-non cas–de la base de données de pharmacovigilance de l’Organisation Mondiale de la Santé (VigiBase®) a été réalisée entre le 1er janvier 2020 et le 10 juin 2020. La fréquence des notifications de COVID-19 concernant chaque classe de DMARDs identifiée a été comparée à celle des notifications de COVID-19 concernant tous les autres médicaments, et exprimée en termes de Reporting Odds Ratio (ROR) [intervalle de confiance à 95 %]. Des analyses stratifiées sur l’indication des DMARDs–donc le type de RIC–ont également été réalisées. Résultats Parmi les 980 446 notifications d’effets indésirables identifiés dans VigiBase® pendant la période d’étude, 398 concernaient des cas de COVID-19 chez des patients atteints de RIC traités par DMARD. Cent soixante-dix-sept (44,4 %) patients avaient une polyarthrite rhumatoïde (PR), 120 (30,2 %) une spondylarthrite ankylosante (SA), 93 (23,4 %) un rhumatisme psoriasique (RPs) et 8 (2,0 %) une arthrite juvénile idiopathique. La plupart des cas de COVID-19 ont été signalés sous anti-TNFα (84,2 %). Un signal de disproportionnalité significatif a été trouvé pour les anti-TNFα (ROR=8,31 [7,48–9,23]), en particulier au cours de la PR (ROR=2,96 [2,05–4,28]), de la SA (ROR=2,21 [1,24–3,95]) et du RPs (ROR=4,55 [2,65–7,80]). Un signal de disproportionnalité inverse a été trouvé avec le tocilizumab (ROR=0,12 [0,02–0,88]) et les inhibiteurs de Janus Kinase (JAK) (ROR=0,33 [0,19–0,58]) chez les patients atteints de PR. Discussion Nos résultats sont cohérents avec les données actuelles de la littérature concernant un profil de sécurité favorable des anti-IL-6 et des anti-JAK chez les patients atteints de PR [1]. Une étude récente a montré une association inverse significative entre l’utilisation des anti-TNFα et l’hospitalisation pour COVID-19 chez les patients atteints de RIC (OR=0,40, IC à 95 % [0,19–0,81]) [2]. Ainsi, l’utilisation d’anti-TNFα pourrait potentiellement favoriser la COVID-19, au même titre que d’autres infections virales, mais pourrait également réduire la gravité de la maladie en inhibant l’orage cytokinique. Conclusion Nos résultats suggèrent un profil de sécurité potentiel des anti-IL-6 et des JAK chez les patients atteints de PR. Il existe un signal de disproportionnalité important concernant les anti-TNFα.