Casirivimab and imdevimab (Ronapreve®) are two recombinant human monoclonal antibodies (mAbs) that bind to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein, preventing the virus from entering cells. In March 2021, this drug was granted emergency use authorisation (EUA) in France for early treatment of COVID-19 in patients at increased risk of progression to severe COVID-19. In August/September 2021, the indication was expanded to COVID-19 prevention (pre- or post-exposure prophylaxis) and treatment of hospitalised patients requiring non-invasive oxygen therapy. The aim of the study was to better describe the adverse drug reaction (ADR) profile and detect safety signals of this new drug used in COVID-19 treatment. We described ADR profile with casirivimab/imdevimab reported as suspect/interacting drug to the French pharmacovigilance network and the pharmaceutical company between 17/03/2021 and 30/06/2022. Data presented correspond to the 2 periods of the pharmacovigilance survey: the first carried out by the pharmaceutical company for curative and prophylactic uses and the second by Toulouse university regional pharmacovigilance center (RPVC). A total of 384 reports were analysed and 256 were "serious". ADR profile was comparable between the 2 periods and between curative and prophylactic use, corresponding to expected ADRs such as infusion-related reactions and hypersensitivity, inefficiencies or worsened infections and deaths. Two potential pharmacovigilance signals were also studied: acute pulmonary oedemas and sudden deaths. No pharmacovigilance signal emerged from this 15 months French pharmacovigilance survey. Moreover data from published studies are also reassuring. This pharmacovigilance survey was the first one for the new version of EUA and with a new ADR reporting process i.e. declaration to the RPVC instead of the pharmaceutical company. Casirivimab/imdevimab is no longer used in France today but we continue to monitor this drug for any future evidence of resurgent activity on a new variant of Sars-CoV-2.

During the COVID-19 pandemic, EPI-PHARE, a scientific group in pharmaco-epidemiology created by the French National Agency for the Safety of Medicines and Health Products (ANSM) and the French National Health Insurance (Cnam), has reoriented its work program to enlighten health authorities in this health crisis. By exploiting massive and complex data of the French Health Data System (SNDS) from the beginning of the first lockdown in France in March 2020, we were able to publish numerous results on the use, benefits and risks of medicines, on the risk factors of COVID-19 before and after vaccination, and on the benefits and risks of COVID-19 vaccines. Our results were widely taken into account by the French health authorities and allowed them to take informed decision in this pandemic situation in order to ensure the health of the population.

To limit the spread of the coronavirus disease 2019 (COVID 19), sanitary restrictions have been established since March 2020 in France. These restrictions and the waves of contamination may have had consequences on the use of health products in general, and on the use of contraceptives in particular. We aimed to assess the impact of COVID 19 pandemic from March 16th 2020 to April 30th 2021 in France on reimbursed contraceptives. We analyzed data from the French national health insurance database (SNDS) by extracting all oral contraception (OC), emergency contraception (EC), levonorgestrel-intrauterine system (LNG-IUS), copper-intrauterine device (C-IUD) and contraceptive implant dispensations in 2018, 2019, 2020 and to April 30th 2021. We computed the expected use of contraceptives in 2020 and 2021 without pandemic and its associated sanitary restrictions, by taking the annual trend into account. We assessed the evolution of dispensations by type of contraceptive and by age-groups (≤25 years old, between 25 and 35 and >35 years old) between observed and expected dispensations. After 15months of pandemic, a decrease of all reimbursed contraceptives dispensations had been estimated, compared with what was expected: -2.0% for OC, -5.0% for EC, -9.5% for LNG-IUS, -8.6% for C-IUD, -16.4% for implant. Women under 25years old were the most impacted by the decrease. This national study showed that the impact of the COVID 19 crisis was global on all reimbursed contraceptives, with different levels of impact depending on the type of contraceptive, the age-group and the severity of the restriction. OC dispensing decreased marginally compared with expectations. The decrease in long-acting contraceptives dispensing was more pronounced, especially for the implant. These results call for continued monitoring of contraceptive use over the long term and for prioritizing access to sexual health services during crises, especially among the youngest women who were most affected in this study.

Psychotropics are widely used drugs, especially in the elderly, especially in France. This, and the risks associated to their use, logically led to concerns that resulted in numerous studies, reports, and regulatory actions intending to limit this use. This review objective was to provide an overview of psychotropic use in elderly subjects in France for antipsychotics, antidepressants, and benzodiazepines and related drugs. The narrative review performed is structured in two parts. The first reminds the initial steps of psychotropic use monitoring in the general French population. The second provides information on psychotropic use in elderly in France using the latest open data released by the French Health Insurance system and processed using the dedicated DrugSurv tool developed within the DRUGS-SAFE® and DRUGS-SAFE® programs. This was completed examining the most recent studies regarding psychotropic use in elderly in France, whether they consisted in publications or reports. At least before the COVID-19 epidemic, decreases in psychotropic prevalence of use among the elderly in France could be observed, mostly for antipsychotics or benzodiazepines (e.g. antipsychotics, 2006-2013: 10.3% decrease and benzodiazepines 2012-2020: decrease from 30.6% to 24.7% in subjects aged ≥65). Psychotropic prevalence of use remained however very high overall (e.g. antidepressants, 2013: 13% in subjects aged 65-74 and 18% in aged ≥65), exceeding that of most other countries, with a significant proportion of inappropriate use (e.g. in 30% of benzodiazepine users, all ages) carrying a clearly identified risks for uncertain benefit. Initiatives have been multiplied at the national level to reduce psychotropic overuse in the elderly. The reported prevalences demonstrate their effectiveness is obviously insufficient. This limited effectiveness is not specific to psychotropics and might reside in a failure to create strong adherence to messages and recommendations. Other levels should be considered, especially regional, for interventions coupled with pharmacoepidemiologic monitoring allowing impact assessment.

Two severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) messenger RNA (mRNA) vaccines, tozinameran/BNT162b2 (Comirnaty®, Pfizer-BioNTech) and elasomeran/mRNA-1273 (Spikevax®, Moderna), were approved by the Food and Drug Administration (FDA) and the European Medicines Agency (EMA) at the end of 2020, less than a year after the start of the coronavirus disease 2019 (COVID-19) pandemic. In France, the health authorities have requested an intensive vaccination campaign, accompanied by a reinforced and active pharmacovigilance surveillance. This surveillance and analysis of real-life data, based on spontaneous reports received by the French Network of Regional PharmacoVigilance Centers (RFCRPV), has enabled to identify numerous pharmacovigilance signals. Some of them, such as myocarditis and heavy menstrual bleeding, have been confirmed as adverse effects of these vaccines. We propose a descriptive review of the main pharmacovigilance signals identified by the RFCRPV concerning vaccines from the mRNA platform. Most pharmacovigilance signals were common to both mRNA vaccines: myocarditis, menstrual disorders, acquired haemophilia, Parsonage-Turner syndrome, rhizomelic pseudo-polyarthritis and hearing disorders. Other signals were more specific, such as arterial hypertension with tozinameran or delayed reaction site injection with elasomeran. This non-exhaustive review illustrates the experience of RFCRPV in identifying and monitoring pharmacovigilance signals related to mRNA vaccines in France during the COVID-19 pandemics, and the crucial role of pharmacological and clinical expertise in this area. It also highlights the predominant contribution of spontaneous reporting in the generation of pharmacovigilance signals, particularly for serious and rare adverse events not detected before marketing.

Oral HIV pre-exposure prophylaxis (PrEP) has been available and fully reimbursed for people at high risk of sexually acquired HIV infection in France since January 2016. To evaluate the roll-out of PrEP use in France and its real-life effectiveness. The main results of two previously published studies were presented at the second e-congress of the EPI-PHARE scientific interest group on pharmacoepidemiology and public decision support held in June 2022, and are reported in this article. Two studies were carried out using the French National Health Data System (SNDS) covering 99% of the French population. A first study aimed to evaluate the roll-out of PrEP use in France from its implementation until June 2021, globally over the entire study period, including an assessment of the impact of the coronavirus disease 2019 (COVID-19) pandemic that started in February 2020 in France. A second study using a nested case-control design was conducted in a cohort of men at high risk of HIV acquisition included between January 2016 and June 2020 to assess the effectiveness of PrEP in the real world. As of 30 June 2021, a total of 42159 people had initiated PrEP in France. Initiations increased steadily until February 2020, then slowed down sharply from the start of the COVID-19 pandemic and resumed from the first half of 2021. PrEP users were overwhelmingly men (98%), with an average age of 36 years, living in a large urban area (74%), and of whom a minority (7%) were socioeconomically disadvantaged. Throughout the study period, the level of PrEP maintenance from one semester to the next was high (80-90%). However, for 20% of PrEP initiators, no prescription renewals were recorded during the first six months, suggesting a substantial proportion of early treatment discontinuation. A minority (21%) of PrEP renewal prescriptions were made by private practitioners. Among 46706 men at high risk of HIV infection, 256 patients identified with HIV infection were matched with 1213 controls. PrEP was used by 29% of cases and 49% of controls. Overall, PrEP effectiveness reached 60% (95% confidence interval 46% to 71%), and was increased in people with high PrEP use (93% (84% to 97%)), or after excluding periods of treatment discontinuation (86% (79% to 92%)). PrEP effectiveness was significantly reduced in people under 30 years of age (26% (-21% to 54%)) and in socioeconomically disadvantaged people (-64% (-392% to 45%)), for whom low PrEP uptake rates or high PrEP discontinuation rates were frequently observed. PrEP roll-out has been strongly impacted by the COVID-19 pandemic in France. Although it has been substantial among men who have sex with men, additional measures are needed to expand access to PrEP to all other population groups that could benefit from it. Promoting adherence to PrEP (especially among young people and the socioeconomically disadvantaged) will be essential to ensure a higher level of PrEP effectiveness, which has been shown to be lower in real-life settings than in clinical trials.

Post-mRNA coronavirus diseases 2019 (COVID-19) vaccines myocarditis emerged as a rare adverse effect, particularly in adolescents and young adults, and was labeled as such for both vaccines in the summer of 2021. This study aims to summarize the timeline and process of signal detection, substantiation, and quantification of myocarditis cases related to mRNA vaccines in France. The intensive monitoring plan for COVID-19 vaccine safety was based on case-by-case analysis of all cases collected in the French spontaneous reporting database (Base nationale de pharmacovigilance, BNPV). Cases were evaluated by drug safety medical professionals and discussed at a national level for signal detection purposes. Reported cases were compared to the number of vaccine-exposed persons up to September 30th, 2021. Reporting rates (Rr) of myocarditis per 100,000 injections were calculated and stratified according to age, gender, and injection rank of BNT162b2 and mRNA-1273 vaccines. Poisson distribution was used to compute Rrs 95% Confidence Interval (95% CI). The case-by-case analysis detected a possible cluster of myocarditis in April 2021 (5 cases, 4 after the 2nd injection). In June 2021, the signal was substantiated with 12 cases (9 related to BNT162b2, and 3 to mRNA-1273). As of September 2021, almost 73 million BNT162b2 and 10 million mRNA-1273 doses had been injected. The Rr per 100,000 injections was 0.5 (0.5-0.6) for BNT162b2 and 1.1 (95% CI 0.9-1.3) for mRNA-1273. The difference among vaccines was more pronounced after the second injection, particularly in men aged 18-24 years (4.3 [3.4-5.5] for BNT162b2 vs. 13.9 [9.2-20.1] for mRNA-1273) and aged 25-29 years (1.9 [1.2-2.9] vs. 7.0 [3.4-12.9]). The study highlighted the role of the spontaneous reporting system in the detection, assessment, and quantification of myocarditis related to m-RNA vaccines. It suggested from September 2021 that mRNA-1273 was reasonably related to a higher risk of myocarditis than BNT162b2 in people under 30, particularly after the second injection.