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

In its August meeting, the European Medicine Agency (EMA)’s Pharmacovigilance Risk Assessment Committee (PRAC) agreed to monitor the risk of multisystem inflammatory syndrome (MIS) with COVID-19 vaccines and venous thromboembolism with Janssen COVID-19 Vaccine, in addition to issuing a new safety signal for Imbruvica.

PRAC reviewing cases of multisystem inflammatory syndrome in COVID-19 vaccines

The committee is assessing whether there is a risk of multisystem inflammatory syndrome (MIS) with COVID-19 vaccines following a report of MIS with Comirnaty^®. The case occurred in a 17-year old male in Denmark who has since fully recovered.

Some cases of MIS were also reported in the European Economic Area (EEA) following vaccination with other COVID-19 vaccines. MIS has previously been reported following COVID-19 disease; however, the Danish patient had no history of COVID-19.

The EMA stated that MIS is rare and its incidence rate before the COVID-19 pandemic estimated from five European countries was around two to six cases per 100,000 per year in children and adolescents below 20 years of age and below two cases per 100,000 per year in adults aged 20 years or more. At this stage, there is no change to the current EU recommendations for the use of COVID-19 vaccines.

PRAC encouraged all healthcare professionals to report any cases of MIS and other adverse events in people having these vaccines. The committee will now assess the available data on MIS to determine whether the condition can be caused by the vaccine and recommend whether any changes to the product information of the vaccines are needed. EMA and national authorities will provide further updates as necessary.

Monitoring venous thromboembolism cases associated with Janssen COVID-19 Vaccine

As part of the ongoing close safety monitoring of the COVID-19 vaccines, PRAC is reviewing data on cases of venous thromboembolism with the Janssen COVID-19 Vaccine. The EMA emphasised that this safety issue is distinct from the very rare side effect of thrombosis with thrombocytopenia syndrome (TTS).  

Venous thromboembolism was included in the risk management plan for the Janssen COVID-19 Vaccine as a safety issue to be investigated, based on a higher proportion of cases of venous thromboembolism observed within the vaccinated group versus the placebo group in the first clinical studies used to authorise this vaccine.

The committee will assess additional data from two large clinical trials of the vaccine, which are to be submitted shortly by its marketing authorisation holder, to further evaluate whether the condition is linked to the vaccine.

PRAC issues new safety signal for Imbruvica

This direct healthcare professional communication (DHPC) aims to inform healthcare professionals about a new safety signal of sudden or cardiac death with Imbruvica (ibrutinib) when used in combination with rituximab and angiotensin-converting enzyme (ACE) inhibitors. The signal was recognised following a review of the findings of a clinical study.

Imbruvica is a medicine indicated for treating blood cancers, including mantle cell lymphoma, chronic lymphocytic leukaemia (CLL) and Waldenström’s macroglobulinaemia.

An interim analysis of the clinical trial suggested that the risk of sudden or cardiac death in patients on an ACE inhibitor when entering the study was increased in patients randomised to ibrutinib and rituximab, compared to those randomised to fludarabine, cyclophosphamide and rituximab.

While PRAC is reviewing the signal, as a precautionary measure, for patients with CLL currently receiving ibrutinib plus rituximab together with an ACE inhibitor, the committee advises healthcare professionals to reconsider the treatment strategy.

For patients with CLL on ACE-inhibitors who have not yet started treatment with ibrutinib plus rituximab, the PRAC recommend that the treatment strategy should be reconsidered before commencing ibrutinib.

The committee will communicate final conclusions and recommendations as soon as the evaluation has been completed. The DHPC for Imbruvica will be forwarded to EMA’s human medicines committee, CHMP. Following the decision, the DHPC will be disseminated to healthcare professionals by the marketing authorisation holder, according to an agreed communication plan, and published on EMA’s website and in national registers in EU Member States.

Martin Huber to continue as vice-chair of PRAC

The committee has voted to prolong, for another three years, the mandate of Dr Martin Huber as vice-chair of the committee. Dr Huber’s new mandate will take effect from October 2021.