Pharmacovigilance Risk Assessment Committee (PRAC) meeting highlights, Oct 2021

In their latest meeting, the European Medicine Agency (EMA)’s Pharmacovigilance Risk Assessment Committee (PRAC) looked at the risk of myocarditis and pericarditis with Comirnaty^® and Spikevax, among other COVID-19 vaccine risks, and finds no link between sudden or cardiac death with Imbruvica (ibrutinib) when used in combination with angiotensin-converting enzyme (ACE) inhibitors.

PRAC assesses risk of myocarditis and pericarditis with mRNA vaccines

EMA’s safety committee is assessing further data providing more information on the risk of myocarditis and pericarditis following vaccination with COVID-19 vaccines Comirnaty and Spikevax. Myocarditis and pericarditis are inflammatory conditions of the heart. Symptoms can vary but often include breathlessness, a forceful heartbeat that may be irregular (palpitations), and chest pain.

The PRAC had previously reviewed cases of myocarditis and pericarditis spontaneously reported in the European Economic Area (EEA) in July 2021. The review concluded with a recommendation to list both conditions as side effects in the product information for these vaccines.

The committee has now asked the companies that market these vaccines to perform an in-depth review of all published data on the association of myocarditis and pericarditis, including clinical trial data, data from the literature and data available in the public domain. EMA will continue to monitor the vaccines’ safety and effectiveness and will communicate further when new information becomes available.

No link between COVID-19 vaccines and multi-system inflammatory syndrome established

The PRAC has concluded that there is currently insufficient evidence on a possible link between COVID-19 vaccines and very rare cases of multi-system inflammatory syndrome (MIS).

The committee’s assessment is based on the available spontaneous reports and currently does not warrant an update of the product information. The committee encouraged all healthcare professionals to report any cases of MIS that may have occurred after vaccination and other adverse events in people receiving these vaccines. EMA stated that it will continue to closely monitor any new reports of the condition and take appropriate measures if necessary.

PRAC starts review of signal of capillary leak syndrome with Spikevax

The committee has started a review of a safety signal to assess reports of capillary leak syndrome in people who were vaccinated with Spikevax.

Six cases of this very rare disorder were reported in the EudraVigilance database. At this stage, it is not yet clear whether there is a causal association between vaccination and the reports of capillary leak syndrome.

The PRAC will evaluate all the available data to decide if a causal relationship is confirmed or not and the EMA will further communicate on the outcome of the review.

PRAC finds risk of sudden or cardiac death not related to Imbruvica with ACE inhibitors

The committee has concluded the review of a safety signal of sudden or cardiac death with Imbruvica (ibrutinib) when used in combination with ACE inhibitors. Imbruvica is a medicine for treating mantle cell lymphoma, chronic lymphocytic leukaemia (CLL) and Waldenström’s macroglobulinaemia.

Interim data from a clinical trial suggested that the risk of sudden or cardiac death in patients on an ACE inhibitor when entering the study may be increased in patients randomised to ibrutinib and rituximab, compared to those randomised to fludarabine, cyclophosphamide and rituximab.

After reviewing additional analyses from different sources including other clinical trials, the PRAC has concluded that the possible association between treatment with Imbruvica with concomitant use of ACE inhibitors and the risk of sudden or cardiac death does not seem to be plausible.

However, the committee has also decided that although some cardiac adverse reactions are already known for Imbruvica, a further analysis of serious cardiac events is considered necessary in order to determine if these events might be linked to the use of Imbruvica alone and better characterise the risk of cardiotoxicity with the medicine, regardless of ACE inhibitor use.