Highlights of the May 2021 Pharmacovigilance Risk Assessment Committee (PRAC) meeting

The European Medicines Agency (EMA) Pharmacovigilance Risk Assessment Committee (PRAC) has released the highlights of its 2021 May meeting, in which it reviewed several safety signals related to COVID-19 vaccines, including Comirnaty, Janssen COVID-19 Vaccine, Vaxzevria and COVID-19 Vaccine Moderna.

Concluded reviews

Facial swelling with Comirnaty

After reviewing all available evidence, PRAC concluded that there is at least a reasonable possibility of a causal association between the Comirnaty COVID-19 vaccine and the reported cases of facial swelling in people with a history of injections with dermal fillers (soft, gel-like substances injected under the skin). As such the committee has recommended that Comirnaty’s product information be updated to include facial swelling in people with a history of injections with dermal fillers as a side effect in section 4.8 of the summary of product characteristics (SmPC) and in section 4 of the patient information leaflet (PIL). The benefit-risk balance of the vaccine remains unchanged.

Thrombosis with thrombocytopenia syndrome with Janssen COVID-19 Vaccine

Having concluded its review, PRAC confirmed that the benefits of the Janssen COVID-19 Vaccine continue to outweigh the risk of thrombosis (formation of blood clots in the vessels) with thrombocytopenia (low blood platelets) syndrome. Thrombosis with thrombocytopenia syndrome was listed previously in the product information for the Janssen COVID-19 Vaccine. However, the product information will now also include advice that patients who are diagnosed with thrombocytopenia within three weeks of vaccination should be actively investigated for signs of thrombosis. Similarly, patients who present with thromboembolism within three weeks of vaccination should be evaluated for thrombocytopenia. Lastly, thrombosis with thrombocytopenia syndrome will be added as an ‘important identified risk’ in the risk management plan for the vaccine and the marketing authorisation holder must provide a plan to further study the possible underlying mechanisms for these very rare events.

Continuing reviews

Comirnaty and COVID-19 Vaccine Moderna for thrombosis with thrombocytopenia syndrome

PRAC stated it is continuing to closely monitor whether messenger (m)RNA vaccines might also be linked to cases of rare, unusual blood clots with low blood platelets, a side effect that has been reported in Vaxzevria and the Janssen COVID-19 Vaccine. Following a review of reports of suspected side effects, the PRAC considers at this stage that there is no safety signal for the mRNA vaccines, as only few cases of blood clots with low blood platelets have been reported. When seen in the context of the exposure of people to the mRNA vaccines, these numbers are extremely low, lower than that in people who have not been vaccinated. In addition, these cases do not seem to present the specific clinical pattern observed with Vaxzevria and the Janssen COVID-19 Vaccine. Overall, the current evidence does not suggest a causal relation; however the EMA will continue to monitor closely.

Guillain-Barre syndrome with AstraZeneca’s Vaxzevria

As part of the enhanced safety monitoring for COVID-19 vaccines, the EMA requires marketing authorisation holders to submit pandemic summary safety reports every month which are reviewed by PRAC for any areas of concern that may need to be investigated.

The PRAC is currently reviewing data on cases of Guillain-Barre syndrome (GBS) reported following vaccination with AstraZeneca’s COVID-19 vaccine, Vaxzevria. GBS is an immune system disorder that causes nerve inflammation and can result in pain, numbness, muscle weakness and difficulty walking. GBS was identified during the marketing authorisation process as a possible adverse event requiring specific safety monitoring activities. PRAC has requested the marketing authorisation holder to provide further detailed data, including an analysis of all the reported cases in the context of the next pandemic summary safety report.

Myocarditis with Comirnaty and COVID-19 Vaccine Moderna

EMA is aware of cases of myocarditis (inflammation of the heart muscle) and pericarditis (inflammation of the membrane around the heart) mainly reported following vaccination with Comirnaty. There is currently no indication that these cases are caused to the vaccine; however, the committee has requested the marketing authorisation holder to provide further detailed data, including an analysis of the events according to age and gender, in the context of the next pandemic summary safety report and will consider if any other regulatory action is needed. Additionally, the PRAC has requested the marketing authorisation holder for COVID-19 Vaccine Moderna – another mRNA vaccine – to monitor similar cases with their vaccine and to also provide a detailed analysis of the events in the context of the next pandemic summary safety report.