Rapid safety assessment of a seasonal intradermal trivalent influenza vaccine

Abstract

Seasonal influenza vaccine formulations must be updated annually to correspond to the influenza viruses in circulation. This was an uncontrolled, open-label, multi-center phase IV study conducted in Belgium to comply with interim European Medicines Agency (EMA) guidelines for rapidly evaluating the safety of newly formulated seasonal influenza vaccines. Adult volunteers received one dose of the 2014-2015 Northern Hemisphere formulation of licensed intradermal trivalent influenza vaccine at either the standard dose (9µg hemagglutinin/strain for 18−59 year-olds) or the high dose (15µg hemagglutinin/strain for ≥ 60 year-olds). Vaccinees recorded their solicited reactions and unsolicited adverse events for 7 d after vaccination. Solicited reaction frequencies were compared to historical reference values obtained from previous clinical trials to determine if the new formulations were excessively reactogenic or allergenic. A total of 210 participants (105 per age group) were included and vaccinated in October 2014. In both groups, pain, erythema, and pruritus were the most common solicited injection site reactions, and headache and myalgia were the most common solicited systemic reactions. Although the frequencies of shivering in 18−59 year-olds and malaise in ≥ 60 year-olds were higher than historical reference values, they were not considered indicative of excessive reactogenicity because almost all of these reactions were mild. The study design was endorsed by the EMA and permitted the reactogenicity of both vaccine formulations to be assessed within one month by collecting adverse events for 7 d. Both formulations exhibited acceptable safety profiles although this should be confirmed through forthcoming enhanced post-marketing safety surveillance systems.

Enhanced Safety Surveillance of Seasonal Quadrivalent Influenza Vaccines in English Primary Care: Interim Analysis

“…This seems to suggest that use of ADR cards together with EHR system weekly data extractions is an appropriate tool for adverse event surveillance. Other approaches have been proposed to meet EMA requirements [ 35 ].…”

Challenges in implementing yearly enhanced safety surveillance of influenza vaccination in Europe: lessons learned and future perspectives

“…4,11,12 Four complete influenza seasons have elapsed since the release of the EMA interim and updated guidance on ESS and several groups (i.e., academic groups, public health representatives, and manufacturers) have reported the outcome of their ESS investigations for the following seasons; 2014/15 (two studies), 2015/16 (three studies), 2016/17 (three studies); and 2017/18 (three studies) ( Table 1). Most studies are published [13][14][15][16][17][18][19][20] (or accepted for publication 21 ), and one additional study evaluating GSKs Fluarix Tetra for the 2017/18 (NCT03278067) season is also completed. 22 The vaccines studied were Sanofi Pasteur's Intanza (9 and 15 µg), Vaxigrip and Vaxigrip Tetra, GSK's Fluarix Tetra/ Alpharix Tetra and AstraZeneca's Fluenz Tetra.…”

“…Of 11 studies reported here, 9 employed the EPS methodology,1 was set up as a non-interventional voluntary PASS, and 1 was a passive surveillance using a population-based description study design (Table 1). To facilitate passive reporting of AEIs, five of the EPS studies used a combination of Adverse Event Reporting Cards (AERCs) and data from patients' EHR,; 15,17,19,21,22 one study used daily diaries and patient interviews, 13 one used a webbased questionnaire with daily reminders via text message, 18 one used telephone interview 20 , and another principally used telephone interview although a minority used web-based questionnaire. 16 The PASS study employed a web-based questionnaire issued 14 days after vaccination.…”

The Skin Immune System and Intradermal Delivery of Vaccines: A Review

“…In the second group, 54% documented a reaction at the site of application and 32% reported a systemic reaction. In both groups the reactions were mild and transitory [32].…”