ABSTRACT
Résumé La pandémie secondaire au virus SARS-CoV2 s'est traduite, pour la pharmacovigilance institutionnelle française, par une « crise sanitaire » en 2 temps : la phase coronavirus disease 2019 - « COVID-19 » pendant laquelle les missions des centres régionaux de pharmacovigilance (CRPV) étaient de détecter un impact des médicaments sur cette maladie, qu'il s'agisse du rôle éventuellement aggravant de certains médicaments ou d'une modification du profil de sécurité de médicaments utilisés pour la prise en charge de la COVID-19. La seconde phase a fait suite à la mise à disposition des vaccins contre la COVID-19, pendant laquelle les missions des CRPV étaient de détecter le plus précocement possible, tout nouvel effet indésirable grave, source d'un potentiel signal qui modifierait le rapport bénéfices/risques d'un vaccin et nécessiterait la mise en place de mesures de sécurité sanitaire. Pendant ces 2 périodes, la détection de signal est restée le cœur de métier des CRPV. Les CRPV ont du s'organiser pour prendre en charge l'augmentation historique de la volumétrie de déclarations et de demandes d'avis. Les CRPV en charge du suivi des vaccins ont fait face à une activité démesurée sur une longue durée, afin de synthétiser l'ensemble des déclarations, d'identifier, en temps réel, l'émergence de signaux et de produire un rapport hebdomadaire. L'organisation nationale mise en place avec l'Agence nationale de sécurité du médicament et des produits de santé a permis de relever le challenge que représentait un tel suivi instantané des vaccins. Le Réseau français des CRPV a su s'adapter en faisant preuve d'agilité et de flexibilité et en démontrant son efficacité dans la détection précoce de signaux. Cette crise a également confirmé la supériorité de la détection manuelle/humaine des signaux en terme de puissance et d'efficience pour détecter rapidement un nouvel effet indésirable médicamenteux et prendre rapidement des mesures de réduction du risque. Pour maintenir la performance des CRPV français dans la détection de tels signaux et surveiller tous les médicaments comme ils doivent l'être un nouveau modèle de financement permettant de corriger l'inadéquation des moyens d'expertise des CRPV au regard de la volumétrie des déclarations est maintenant nécessaire.
ABSTRACT
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) pandemic virus was a "health crisis" and a significant burden also for the French pharmacovigilance system. It took its toll in 2 phases, the first being in early 2020 when very little was known, and during which the missions of the 31 Regional Pharmacovigilance Centers (RPVCs) from university hospitals were to detect adverse reactions of drugs used in the context of the disease. Whether as a possible aggravating role on COVID-19, or displaying a different safety profile during its course, or to assess safety of curative treatment, this phase preceded that of the arrival of dedicated vaccines. Then the RPVCs' missions were to detect, as early as possible, any new serious adverse effect leading to a potential signal that would modify the benefit/risk ratio of a vaccine and require the implementation of health safety measures. During these two distinct periods, signal detection remained the core business of the RPVCs. Each RPVC had to organize itself to handle an unprecedented surge of declarations and requests for advice, from health care professionals and patients alike. "Leading" RPVCs, who were in charge of monitoring vaccines, had to deal with an extraordinary workload (still going on to this date), to generate in real-time and on a weekly basis, a summary of all the adverse drug reaction (ADR) reports as well as an extended analysis of the different safety signals. The organization put in place at the beginning of the health crisis, adapted to the context of the vaccines, allowed to meet the challenge of real-time pharmacovigilance monitoring, and to identify many safety signals. Efficient "short-circuits exchanges" with the French Regional Pharmacovigilance Centers Network (RPVCN) were paramount to the National Agency for the Safety of Medicines and Health Products (ANSM) to develop an optimal collaborative partnership. The French RPVCN has shown at this occasion both agility and flexibility, swiftly adapting to vaccine- and media-related unrest, and demonstrated its effectiveness in the early detection of safety signals. This crisis also confirmed the superiority of manual/human signal detection over automated ones, as the most effective and powerful tool to date to rapidly detect and validate a new ADR and enable to elaborate rapid risk reduction measures. To maintain the performance of French RPVCN in signal detection and to monitor all drugs as they should, and as expected by our fellow citizens, a new funding model should be considered.
ABSTRACT
The pandemic subsequent to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus resulted, for the French institutional pharmacovigilance, in a "health crisis" in 2 phases: the coronavirus disease 2019 - "COVID-19" phase during which the missions of the Regional Pharmacovigilance Centres (RPVC) were to detect a possible impact of drugs on this disease, as whether existed a possible aggravating role of certain drugs, or the safety profile of drugs used for the management of COVID-19 could evolve. The second phase followed the availability of COVID-19 vaccines, during which the RPVCs' missions were to detect as early as possible any new serious adverse effect, source of a potential signal that would modify the benefit/risk ratio of a vaccine and require the implementation of health safety measures. During these two periods, signal detection remained the core business of the RPVCs. The RPVCs had to organize themselves to handle an historical surge of declarations and requests for advice, whereas the RPVCs in charge of monitoring vaccines had to deal with an extraordinary dense activity over a long period of time, in order to produce in real time and on a weekly basis, a summary of all the declarations and an analysis of safety signals. The national organization put in place made it possible to meet the challenge of real-time pharmacovigilance monitoring of 4 vaccines with conditional marketing authorizations. Short-circuit efficient exchanges with the French Regional Pharmacovigilance Centres Network was paramount for the French National Agency for medicines and health products (Agence nationale de sécurité du médicament et des produits de santé) to develop an optimal collaborative partnership. The RPVC network has shown agility and flexibility, has been able to adapt swiftly and demonstrated its effectiveness in the early detection of safety signals. This crisis confirmed the superiority of manual/human signal detection as the most effective and powerful tool to date, to rapidly detect a new adverse drug reaction and enable to elaborate rapid measures of risk reduction. In order to maintain the performance of French RPVCs in signal detection and to monitor all drugs as they should and as expected by our fellow citizens, a new funding model correcting the inadequacy of RPVCs' expertise resources in relation to the volume of reports should be considered.
ABSTRACT
Résumé Dans le cadre de la campagne de vaccination contre la COVID-19, l'Agence nationale de sécurité du médicament et l'ensemble des 31 centres régionaux de pharmacovigilance ont été mobilisés dans un dispositif exceptionnel de surveillance renforcée de pharmacovigilance des vaccins. Concernant les vaccins à adénovirus, Vaxzévria® et Jcovden®, ce dispositif national basé sur l'analyse quotidienne des cas notifiés d'effets indésirables, a permis d'identifier précocement des signaux de sécurité, certains validés depuis, d'autres encore en cours d'analyse, communs avec les vaccins à ARNm ou plus spécifiques tels que les thrombopénies thrombosantes immunitaires induites par le vaccin. Venu en complément des actions européennes et internationales, ce suivi a contribué à mieux définir le profil de sécurité de ces vaccins et conduit à redéfinir la stratégie vaccinale dans notre pays. Même si aujourd'hui ces vaccins n'ont plus de place dans la stratégie vaccinale nationale, ils restent utilisés dans d'autres pays à qui l'expérience acquise pourra être utile de même qu'elle permettra d'alimenter la réflexion sur de futures thérapeutiques faisant intervenir des vecteurs viraux.
ABSTRACT
As part of the COVID-19 vaccination campaign, the National Agency for the Safety of Medicines and Health Products and all 31 regional pharmacovigilance centers were mobilized in an exceptional reinforced vaccine pharmacovigilance surveillance system. Concerning adenovirus vaccines, Vaxzévria® and Jcovden®, this national system, based on the daily analysis of notified cases of adverse events, has allowed the early identification of safety signals, some of which have been validated, others still under analysis, common to mRNA vaccines or more specific of adenovirus vaccines such as Vaccine Induced Immune Thrombocytopenia. Complementing european and international actions, this follow-up has contributed to a better definition of the safety profile of these vaccines and has led to redefine the vaccine strategy in our country. Although today these two vaccines have no longer place in the national vaccine strategy, they are still used in other countries, where the experience acquired could be useful and will contribute to fuel the reflection on future therapies involving viral vectors.
ABSTRACT
Cases of adult-onset Still's disease (AOSD) have been reported after COVID-19 vaccination. Here we provide a comprehensive description and analysis of all cases of AOSD reported in the literature and in pharmacovigilance databases through April 2022. Disproportionality analyses of pharmacovigilance data were performed in order to further explore the association between vaccination and AOSD. We included 159 patients, 144 from the World Health Organization pharmacovigilance database and 15 from the literature. Detailed clinical characteristics were described for the cases from the literature and from the French pharmacovigilance database (n = 9). The cases of AOSD after COVID-19 vaccination concerned women in 52.2% of cases. The median age was 43.4 years. More than 80% of AOSD reports occurred during the first three weeks and concerned mostly the BNT162b2 mRNA vaccine. We identified 14.5% of disease flare with a median time-to-onset of AOSD flare-up significantly shorter than for the new onset form. More than 90% patients received steroids. Although all cases were considered serious and required hospitalization, most cases presented a favorable outcome (67.1%) with a good response to corticosteroid therapy with a mean time to recovery of 7.2 days. Disproportionality analyses suggested that AOSD was associated with COVID-19 vaccines as well as other vaccines. AOSD was nearly five times more frequently reported with COVID-19 vaccines than with all other drugs. Clinicians should be informed about the potential risk of AOSD onset or flare following COVID vaccines and the importance of its early detection to optimize its management.
Subject(s)
COVID-19 Vaccines , COVID-19 , Still's Disease, Adult-Onset , Adult , Female , Humans , BNT162 Vaccine , COVID-19/epidemiology , COVID-19/prevention & control , COVID-19 Vaccines/adverse effects , Still's Disease, Adult-Onset/diagnosis , Still's Disease, Adult-Onset/drug therapy , Still's Disease, Adult-Onset/epidemiology , Vaccination/adverse effectsABSTRACT
Vaccine-induced immune thrombotic thrombocytopenia is a rare syndrome following the ChAdOx1 nCov-19 or Ad26.COV2.S vaccine. Reported patients developed mainly venous thrombosis. We describe a case of a young healthy women suffering from acute ischemic stroke due to large vessel occlusion without cerebral venous thrombosis 8 days after vaccination and its consequences on recanalization strategy. Considering the thrombocytopenia, intravenous thrombolysis was contraindicated. She underwent mechanical thrombectomy with complete recanalization and dramatically improved clinically. Positive detection of anti-PF4-heparin-antibodies confirmed vaccine-induced immune thrombotic thrombocytopenia diagnosis. In case of acute ischemic stroke after recent ChAdOx1 nCov-19 or Ad26.COV2.S vaccine, platelet count should be systematically checked before giving thrombolysis, and direct mechanical thrombectomy should be proposed in patients with large vessel occlusion.
Subject(s)
COVID-19 Vaccines/adverse effects , Ischemic Stroke/therapy , Purpura, Thrombotic Thrombocytopenic/therapy , Thrombectomy , Vaccination/adverse effects , Adult , Antibodies/blood , Blood Platelets/immunology , COVID-19 Vaccines/administration & dosage , ChAdOx1 nCoV-19 , Female , Heparin/immunology , Humans , Ischemic Stroke/blood , Ischemic Stroke/chemically induced , Ischemic Stroke/diagnosis , Platelet Factor 4/immunology , Purpura, Thrombotic Thrombocytopenic/blood , Purpura, Thrombotic Thrombocytopenic/chemically induced , Purpura, Thrombotic Thrombocytopenic/diagnosis , Treatment OutcomeABSTRACT
In this special issue, we present the main highlights of the first weeks of pharmacovigilance monitoring of coronavirus disease 2019 (COVID-19) vaccines in this unprecedented situation in France: the deployment of a vaccination during an epidemic period with the aim of vaccinating the entire population and the intense pharmacovigilance and surveillance of these vaccines still under conditional marketing authorizations. In this unprecedented situation, the cross approach and interaction between the French pharmacovigilance network and French National Agency for the Safety of Medicines and Health Products (ANSM) has been optimized to provide a real-time safety related to COVID-19 vaccines. Every week, pair of regional pharmacovigilance centers gathered safety data from the French pharmacovigilance network, to acutely expertise all the adverse drug reactions (ADRs) reported with each COVID-19 vaccine within a direct circuit with ANSM. Results of this expertise are presented and discussed with ANSM in order to raise safety signals and take appropriate measures if necessary. These reports are then published online. At the 25th of March 2021, more than 9 815 000 doses were injected and 20,265 ADRs were reported, mostly non-serious (76%). Several potential or confirmed signals were raised at the european level for those vaccines and others ADRs are under special attentions. This underlines the adaptiveness of the French pharmacovigilance system to both the identification of new patient profiles experiencing ADRs and the evolution of the vaccine strategy. Such an efficiency is necessary to manage a careful and acute surveillance of these new COVID-19 vaccines for and to face the pandemic at the same time.