Danish Medicines Agency establishes that chronic urticaria could be a side effect of the Spikevax vaccine

05 April 2024

The European Pharmacovigilance Risk Assessment Committee (PRAC) has reassessed if chronic urticaria could be a side effect after vaccination with the Spikevax vaccine from Moderna. This follows a review from the Danish Medicines Agency, which has investigated data and reports from patients across the European countries.

The PRAC concluded in 2022 that an allergic reaction in the form of non-chronic urticaria in very rare cases might occur as a side effect of the two COVID-19 vaccines that are used in Denmark: Spikevax from Moderna and Comirnaty from Pfizer/BioNTech. However, at that time, evidence was insufficient to conclude that the vaccines might also cause chronic urticaria.

The Danish Medicines Agency has subsequently carried out further investigations to find out if chronic urticaria could be a possible side effect. This required a significant effort throughout 2023; the pharmacovigilance department has partly reviewed all the side effect reports involving chronic urticaria received by the Danish Medicines Agency and has partly collected and analysed data from other sources, including data from the Danish health registers and reports from other EU countries.

The review of these cases led the Danish Medicines Agency to raise, and conclude on, a so-called safety signal, which it submitted to the PRAC, having found that there is sufficient evidence to conclude that chronic urticaria could be a side effect of the Spikevax vaccine. The Danish Medicines Agency has reviewed both the Spikevax vaccine and the far more widely used Comirnaty vaccine. No evidence for corresponding vaccine-related issues were noted for the latter.

In January, the PRAC considered the Danish safety signal and decided, based on the Danish Medicines Agency’s conclusions, that the product information should be updated in future to add chronic urticaria as a side effect of Spikevax.  

Relationship found in 286 of 360 cases

The background for the Danish suspicion is a relatively large number of reports in Denmark. In addition, Denmark is PRAC rapporteur for the Spikevax vaccine, which means that the Danish Medicines Agency assumes special responsibility for the safety monitoring of this particular vaccine for the entire EU. In addition to investigating Danish cases, the Danish Medicines Agency has also collected information on cases from other EU countries.

“We have assessed a total of 360 cases of which the vast majority are from Denmark, but we also received a significant amount of reports from Germany, Switzerland and Italy. In 58 of these cases, we assessed it likely that the patient’s development of chronic urticaria is related to the vaccine, and in 228 cases we assessed that a link to the vaccine is possible,” explains Martin Zahle Larsen, team leader at the Danish Medicines Agency.

It is common practice in the monitoring and evaluation of side effect reports to classify a suspected side effect as either likely, possible or unlikely. The classification depends on the strength of evidence that a symptom may be caused by the medicinal product, or if other factors are considered to be more likely causes in the specific case. 

The Danish investigation shows that the vast majority of cases of chronic urticaria occurred 7-13 days after the third vaccine dose in people given the Spikevax vaccine. The investigation also showed that persons given the Spikevax vaccine have a three times higher risk of developing chronic urticaria compared to the general population and that the risk of developing chronic urticaria after vaccination with Spikevax is particularly higher in younger men.

Chronic urticaria to be included in the package leaflet

The assessment from PRAC has been reviewed by the EMA’s Committee for Medicinal Products for Human Use (CHMP). The CHMP has agreed that the product information of the Spikevax vaccine should be updated to add chronic urticaria as a possible side effect. This now awaits the final approval by the European Commission following which the company responsible for the vaccine will update the vaccine’s product information for healthcare professionals and the package leaflet.


Read more about the Danish investigation in this PDF poster (in Danish only)

Read the assessment of the PRAC (ema.europa.eu)