Meeting highlights from the Pharmacovigilance Risk Assessment Committee (PRAC) 29 November – 2 December 2021

EMA’s safety committee (PRAC) has assessed recent data on the known risk of myocarditis and pericarditis following vaccination with COVID-19 vaccines Comirnaty and Spikevax (previously COVID-19 Vaccine Moderna). This review included two large European epidemiological studies. One study was conducted using data from the French national health system (Epi-phare) and the other one was based on Nordic registry data.

Overall, the outcome of the review confirms the risk of myocarditis and pericarditis, which is already reflected in the product information for these two vaccines, and provides further details on these two conditions.

Based on the reviewed data, the PRAC has determined that the risk for both of these conditions is overall “very rare”, meaning that up to one in 10,000 vaccinated people may be affected. Additionally, the data show that the increased risk of myocarditis after vaccination is highest in younger males.

The PRAC has recommended updating the product information accordingly.

Myocarditis and pericarditis can develop within just a few days after vaccination, and have primarily occurred within 14 days. They have more often been observed after the second vaccination.

The French and Nordic studies provide estimates of the number of extra cases of myocarditis in younger males following the second dose, compared to unexposed persons of the same age and gender.

For Comirnaty, the French study shows that, in a period of seven days after the second dose, there were about 0.26 extra cases of myocarditis in 12- to 29-year old males per 10,000 compared to unexposed persons. In the Nordic study, in a period of 28 days after the second dose, there were 0.57 extra cases of myocarditis in 16- to 24-year old males per 10,000 compared to unexposed persons.

In the case of Spikevax, the French study showed that in a period of seven days after the second dose there were about 1.3 extra cases of myocarditis in 12- to 29-year old males per 10,000 compared to unexposed persons. The Nordic study shows that in a period of 28 days after the second dose of Spikevax there were around 1.9 extra cases of myocarditis in 16- to 24-year-old males per 10,000 compared to unexposed persons.

Myocarditis and pericarditis are inflammatory conditions of the heart that present a range of symptoms, often including breathlessness, a forceful heartbeat that may be irregular (palpitations), and chest pain. Available data suggest that the course of myocarditis and pericarditis following vaccination is not different from myocarditis or pericarditis in general.

EMA will continue to closely monitor this issue and will communicate further when new information becomes available.

EMA confirms that the benefits of all authorised COVID-19 vaccines continue to outweigh their risks, given the risk of COVID-19 illness and related complications, and as scientific evidence shows that they reduce deaths and hospitalisations due to COVID-19.

Glossary:

• Safety signal assessments. A safety signal is information which suggests a new potentially causal association, or a new aspect of a known association between a medicine and an adverse event that warrants further investigation. Safety signals are generated from several sources such as spontaneous reports, clinical studies and the scientific literature. More information can be found under ‘Signal management‘.
• Periodic safety update reports, abbreviated as PSURs, are reports prepared by the marketing authorisation holder to describe the worldwide safety experience with a medicine in a defined period after its authorisation. PSURs for medicinal products that contain the same active substance or the same combination of active substances but have different marketing authorisations and are authorised in different EU Member States, are jointly assessed in a single assessment procedure. More information can be found under ‘Periodic safety update reports: questions and answers‘.
• Risk management plans, abbreviated as RMPs, are detailed descriptions of the activities and interventions designed to identify, characterise, prevent or minimise risks relating to medicines. Companies are required to submit an RMP to EMA when applying for a marketing authorisation. RMPs are continually updated throughout the lifetime of the medicine as new information becomes available. More information is available under ‘Risk-management plans‘.
• Post-authorisation safety studies, abbreviated as PASSs, are studies carried out after a medicine has been authorised to obtain further information on its safety, or to measure the effectiveness of risk-management measures. The PRAC assesses the protocols (aspects related to the organisation of a study) and the results of PASSs. More information can be found under ‘Post-authorisation safety studies‘.
• Referrals are procedures used to resolve issues such as concerns over the safety or benefit-risk balance of a medicine or a class of medicines. In a referral related to safety of medicines, the PRAC is requested by a Member State or the European Commission to conduct a scientific assessment of a particular medicine or class of medicines on behalf of the EU. More information can be found under referral procedures.
• Pandemic summary safety reports have been introduced as part of the enhanced safety monitoring of COVID-19 vaccines. Marketing authorisation holders are required to submit these reports to EMA on a monthly basis. Their submission complements the submission of PSURs. For more information see EMA’s pharmacovigilance plan for COVID-19 vaccines.

Ongoing referrals