ABSTRACT
Introduction: Web reporting is mandatory in Europe, but in the surveillance of COVID-19 vaccines specific web forms or apps were developed in several EU member states [1]. In UK for example, a native app for reporting was introduced in 2015. In Germany, a specific native app (SafeVac) was introduced in 2021, associated to an active surveillance project. In both countries a modified web form for covid-19 vaccines is present. In Italy no different web form or app for covid-19 vaccines-AEFI reporting were developed. In the Italian Veneto region, a progressive web app (Vigicovid) was developed and added to the Italian web form (Vigifarmaco) from February 2021. Objective(s): To investigate the impact of Apps on spontaneous reporting for COVID-19 vaccines in these three countries in 2021. Method(s): The reports from UK and Germany in the period January- December 2021 were analyzed in VigiBase, the WHO global database of reported potential side effects of medicinal products, developed and maintained by Uppsala Monitoring Centre. Reports from the Apps were identified through the national country code. Reports in Veneto Region were analyzed in the regional database in the period February-December 2021. Reports sent from the Veneto vaccination registry through a direct link to spontaneous reporting database were excluded. Result(s): In 2021 UK submitted 450,819 AEFIs (56% serious, 85% from patients) to VigiBase, out of which 13,834 (3%) via the App (56% serious). In the same period Germany submitted 176,063 AEFIs (18% serious, 94% from patients) to VigiBase, 13,043 (7%) of which were sent via SafeVac (6% serious). Patients also contributed to Appreporting (86% in the UK vs 85% on the global level and 100% vs 94% on the global level) in UK and Germany, respectively. During the study period February 2021-December 2021 VigiBase received 10,885 (15% serious, 48% from patients) AEFI reports from the Veneto region, 4,568 (42%) of which submitted by App Vigicovid (10% serious) with 2,634 (58%) reports submitted by citizens. Conclusion(s): The Apps developed in UK and Germany had a limited impact on spontaneous reporting in comparison to the usual reporting (with specific web forms). The progressive web app Vigicovid had a more relevant impact, particularly among citizens.
ABSTRACT
Introduction: After many months from the COVID-19 pandemic beginning, several anti-spike monoclonal antibodies (mAbs) and, more recently, other antiviral drugs for COVID-19 treatment in nonhospitalized patients have been marketed. Specifically, those drugs are indicated for SARS-CoV-2 infection early treatment in outpatient adults at high risk of developing severe COVID-19 [1]. Objective(s): To evaluate the post-marketing safety profile of antivirals drugs used for early COVID-19 treatment, using the World Health Organization global spontaneous reporting database (VigiBase). Method(s): From VigiBase we identified all the individual case safety reports (ICSRs) of marketed mAbs (regdanvimab, sotrovimab, casirivimab/imdevimab, bamlanivimab/etesevimab and, specifically for COVID-19 prevention in immunocompromised patients, tixagevimab/ cilgavimab) and other antiviral therapies for COVID-19 early treatment (remdesivir, nirmatrelvir/ritonavir, molnupiravir). We performed a descriptive analysis of ICSRs recorded in VigiBase of patients' demographics (age, sex, continent of origin) type of reporter, adverse drug reactions (ADRs) (Preferred Term level) and the Important Medical Events (IMEs), from their marketing date to May 4, 2022. In addition, we conducted a disproportional analysis using Reporting Odds Ratio (ROR), along with 95% confidence intervals (CIs), by comparing the frequency of ADRs (System Organ Class level) for each drug of interest with distribution of all ADRs from the whole database, excluding vaccines, reported in the same period. Result(s): Overall, up to 4th May,2022, 15,437 ICSRs of anti-spike mAbs (casirivimab/imdevimab: 27.2%;bamlanivimab/etesevimab: 7.3%;sotrovimab 3.3%;tixagevimab/cilgavimab 2.7% regdanvimab: 0.2%) and other antivirals (remdesivir: 54.5%;nirmatrelvir/ritonavir: 4.3%;molnupiravir 0.5%) from VigiBase were retrieved. ICSRs mainly involved females and 45-64 years old. The percentage of ICSRs that included IMEs was 32.4%. Overall, the most frequently reported ADRs were infusion-related reaction for both casirivimab/ imdevimab (20.1%) and bamlanivimab/etesevimab (19.3%), pyrexia for regdanvimab (30.0%) and sotrovimab (8.1%), increased alanine aminotransferase for remdesivir (13.3%), dysgeusia for nirmatrelvir/ ritonavir (39.5%), and diarrhoea for molnupiravir (18.8%). Overall, statistically significant RORs were observed for "Investigations" with remdesivir (N = 3163;ROR: 5.56;95% CI 5.32-5.81), "Gastrointestinal disorders" for molnupiravir (N = 178;ROR: 3.43;95% CI 2.82-4.17) and "Vascular disorders" for sotrovimab (N = 51;ROR: 2.07;95% CI 1.55-2.76). Conclusion(s): This study shows that the safety profile of anti-spike mAbs and other newly marketed antiviral therapies for the early treatment of COVID-19 is overall favourable. The most frequently reported ADRs in VigiBase are in line with those reported in the pivotal trials and Summary of Product Characteristics for all investigated antiviral drugs. The disproportional analysis identified some potential signals requiring further investigation.
ABSTRACT
Introduction: Web reporting is mandatory in Europe, but in the surveillance of COVID-19 vaccines specific web forms or apps were developed in several EU member states [1]. In UK for example, a native app for reporting was introduced in 2015. In Germany, a specific native app (SafeVac) was introduced in 2021, associated to an active surveillance project. In both countries a modified web form for covid-19 vaccines is present. In Italy no different web form or app for covid-19 vaccines-AEFI reporting were developed. In the Italian Veneto region, a progressive web app (Vigicovid) was developed and added to the Italian web form (Vigifarmaco) from February 2021. Objective: To investigate the impact of Apps on spontaneous reporting for COVID-19 vaccines in these three countries in 2021. Methods: The reports from UK and Germany in the period JanuaryDecember 2021 were analyzed in VigiBase, the WHO global database of reported potential side effects of medicinal products, developed and maintained by Uppsala Monitoring Centre. Reports from the Apps were identified through the national country code. Reports in Veneto Region were analyzed in the regional database in the period February-December 2021. Reports sent from the Veneto vaccination registry through a direct link to spontaneous reporting database were excluded. Results: In 2021 UK submitted 450,819 AEFIs (56% serious, 85% from patients) to VigiBase, out of which 13,834 (3%) via the App (56% serious). In the same period Germany submitted 176,063 AEFIs (18% serious, 94% from patients) to VigiBase, 13,043 (7%) of which were sent via SafeVac (6% serious). Patients also contributed to Appreporting (86% in the UK vs 85% on the global level and 100% vs 94% on the global level) in UK and Germany, respectively. During the study period February 2021-December 2021 VigiBase received 10,885 (15% serious, 48% from patients) AEFI reports from the Veneto region, 4,568 (42%) of which submitted by App Vigicovid (10% serious) with 2,634 (58%) reports submitted by citizens. Conclusion: The Apps developed in UK and Germany had a limited impact on spontaneous reporting in comparison to the usual reporting (with specific web forms). The progressive web app Vigicovid had a more relevant impact, particularly among citizens.
ABSTRACT
Introduction: After many months from the COVID-19 pandemic beginning, several anti-spike monoclonal antibodies (mAbs) and, more recently, other antiviral drugs for COVID-19 treatment in non-hospitalized patients have been marketed. Specifically, those drugs are indicated for SARS-CoV-2 infection early treatment in outpatient adults at high risk of developing severe COVID-19 [1]. Objective: To evaluate the post-marketing safety profile of antivirals drugs used for early COVID-19 treatment, using the World Health Organization global spontaneous reporting database (VigiBase). Methods: From VigiBase we identified all the individual case safety reports (ICSRs) of marketed mAbs (regdanvimab, sotrovimab, casirivimab/imdevimab, bamlanivimab/etesevimab and, specifically for COVID-19 prevention in immunocompromised patients, tixagevimab/cilgavimab) and other antiviral therapies for COVID-19 early treatment (remdesivir, nirmatrelvir/ritonavir, molnupiravir). We performed a descriptive analysis of ICSRs recorded in VigiBase of patients' demographics (age, sex, continent of origin) type of reporter, adverse drug reactions (ADRs) (Preferred Term level) and the Important Medical Events (IMEs), from their marketing date to May 4, 2022. In addition, we conducted a disproportional analysis using Reporting Odds Ratio (ROR), along with 95% confidence intervals (CIs), by comparing the frequency of ADRs (System Organ Class level) for each drug of interest with distribution of all ADRs from the whole database, excluding vaccines, reported in the same period. Results: Overall, up to 4th May,2022, 15,437 ICSRs of anti-spike mAbs (casirivimab/imdevimab: 27.2%;bamlanivimab/etesevimab: 7.3%;sotrovimab 3.3%;tixagevimab/cilgavimab 2.7% regdanvimab: 0.2%) and other antivirals (remdesivir: 54.5%;nirmatrelvir/ritonavir: 4.3%;molnupiravir 0.5%) from VigiBase were retrieved. ICSRs mainly involved females and 45-64 years old. The percentage of ICSRs that included IMEs was 32.4%. Overall, the most frequently reported ADRs were infusion-related reaction for both casirivimab/imdevimab (20.1%) and bamlanivimab/etesevimab (19.3%), pyrexia for regdanvimab (30.0%) and sotrovimab (8.1%), increased alanine aminotransferase for remdesivir (13.3%), dysgeusia for nirmatrelvir/ritonavir (39.5%), and diarrhoea for molnupiravir (18.8%). Overall, statistically significant RORs were observed for "Investigations" with remdesivir (N = 3163;ROR: 5.56;95% CI 5.32-5.81), "Gastrointestinal disorders" for molnupiravir (N = 178;ROR: 3.43;95% CI 2.82-4.17) and "Vascular disorders" for sotrovimab (N = 51;ROR: 2.07;95% CI 1.55-2.76). Conclusion: This study shows that the safety profile of anti-spike mAbs and other newly marketed antiviral therapies for the early treatment of COVID-19 is overall favourable. The most frequently reported ADRs in VigiBase are in line with those reported in the pivotal trials and Summary of Product Characteristics for all investigated antiviral drugs. The disproportional analysis identified some potential signals requiring further investigation.