ABSTRACT
Introduction: Marketed COVID-19 vaccines showed an overall favourable safety profile in pivotal trials. However, those trials did not include high risk/fragile patient categories;hence, close monitoring of COVID-19 vaccine safety in those special cohorts in real-world setting is needed. The European Medicines Agency-funded "Covid- Vaccine-Monitor" project was set up to prospectively measure the incidence of solicited/unsolicited adverse events following COVID- 19 vaccination in several European Countries as reported by vaccinees through web-based questionnaires. Italy is one of the Countries participating in the project as a large network named "ilmiovaccinocovid19 collaborating group". Objective(s): To measure the incidence of vaccinee-reported adverse events following immunization (AEFIs) with marketed COVID-19 vaccines in pregnant and lactating women, pediatrics, immunocompromised, people with history of allergy and people with prior SARSCoV- 2 infection in Italy. Method(s): We performed a prospective cohort study of the abovementioned categories of vaccinees, who were recruited at multiple vaccination centers within 48 hours from either the first or booster COVID-19 vaccine dose administration. After providing informed consent and get registered into the web-app, vaccinees were asked to fill in an electronic baseline questionnaire and 6 follow-up questionnaires at different time points, within 6-month from vaccine administration, in which information on potential vaccine-related AEFIs were collected. We explored and compared the frequency of local and systemic solicited adverse events following first or booster dose for each special cohort and vaccine brands. Result(s): Overall, 1,331 vaccinees (40.4% first dose and 59.6% booster dose) were included in the analysis. Of these, 8.4% were immunocompromised, 32.0% had history of allergy, 25.5% had prior SARS-CoV-2 infection, 23.4% were children/adolescents, 6.2% were pregnant and 4.6% were lactating women (non-mutually exclusive cohorts). Of subjects belonging to at least one cohort, 52.3% reported at least one AEFI following either the first or booster dose. Among all special cohorts, injection site pain was the most frequently reported solicited local AEFI, after both the first (37.5%) and booster (39.5%) dose. As solicited systemic AEFIs, headache (19.0%) was the most frequently reported after the first dose, while malaise (23.7%) and fatigue (23.7%) after the booster dose. The frequency of severe AEFIs was very low following both first dose (0.8%) and booster dose (0.6%). Conclusion(s): Overall, this study confirmed the favourable safety profile of COVID-19 vaccines also in the above-mentioned special categories who have not (or marginally) been included in pivotal trials.
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: Marketed COVID-19 vaccines showed an overall favourable safety profile in pivotal trials. However, those trials did not include high risk/fragile patient categories;hence, close monitoring of COVID-19 vaccine safety in those special cohorts in real-world setting is needed. The European Medicines Agency-funded "Covid-Vaccine-Monitor" project was set up to prospectively measure the incidence of solicited/unsolicited adverse events following COVID-19 vaccination in several European Countries as reported by vaccinees through web-based questionnaires. Italy is one of the Countries participating in the project as a large network named "ilmiovaccinocovid19 collaborating group". Objective: To measure the incidence of vaccinee-reported adverse events following immunization (AEFIs) with marketed COVID-19 vaccines in pregnant and lactating women, pediatrics, immunocompromised, people with history of allergy and people with prior SARS-CoV- 2 infection in Italy. Methods: We performed a prospective cohort study of the abovementioned categories of vaccinees, who were recruited at multiple vaccination centers within 48 hours from either the first or booster COVID-19 vaccine dose administration. After providing informed consent and get registered into the web-app, vaccinees were asked to fill in an electronic baseline questionnaire and 6 follow-up questionnaires at different time points, within 6-month from vaccine administration, in which information on potential vaccine-related AEFIs were collected. We explored and compared the frequency of local and systemic solicited adverse events following first or booster dose for each special cohort and vaccine brands. Results: Overall, 1,331 vaccinees (40.4% first dose and 59.6% booster dose) were included in the analysis. Of these, 8.4% were immunocompromised, 32.0% had history of allergy, 25.5% had prior SARS-CoV-2 infection, 23.4% were children/adolescents, 6.2% were pregnant and 4.6% were lactating women (non-mutually exclusive cohorts). Of subjects belonging to at least one cohort, 52.3% reported at least one AEFI following either the first or booster dose. Among all special cohorts, injection site pain was the most frequently reported solicited local AEFI, after both the first (37.5%) and booster (39.5%) dose. As solicited systemic AEFIs, headache (19.0%) was the most frequently reported after the first dose, while malaise (23.7%) and fatigue (23.7%) after the booster dose. The frequency of severe AEFIs was very low following both first dose (0.8%) and booster dose (0.6%). Conclusion: Overall, this study confirmed the favourable safety profile of COVID-19 vaccines also in the above-mentioned special categories who have not (or marginally) been included in pivotal trials.
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.