Objectives (1) To assess if co-Administration of four-component meningococcal serogroup B vaccine (4CMenB) and other routine vaccines caused an interaction increasing the risk and/or severity of adverse events following immunisation (AEFI) compared with administration at separate visits and (2) to estimate the risk of AEFI recurrence. Design Risk-interval design Setting Three randomised controlled trials conducted in Europe. Participants A total of 5026 healthy 2-month-old to 15-month-old infants. Interventions 4CMenB and routine vaccines (hexavalent combined diphtheria-Tetanus-Acellular pertussis-inactivated polio-Haemophilus influenzae type b-hepatitis B vaccine+seven-valent pneumococcal conjugate vaccine or measles-mumps-rubella-varicella vaccine) administered concomitantly or separately 1 month apart, in regular (2, 4, 6 and 12 months), accelerated (2, 3, 4 and 12 months) or delayed (two doses of 4CMenB at ≥12 months of age) schedules. Outcome measures Primary: Fever (≥38°C) during the first 48 hours post immunisation. Secondary: crying, change in eating habits, diarrhoea, irritability and tenderness at the 4CMenB injection site. Results Compared with separate administration, concomitant administration decreased the overall incidence of fever (≥38°C), 86% versus 75%, and other systemic AEFIs but increased the incidence of 4CMenB injection site tenderness, 55% versus 66%, moderate/severe fevers (≥39°C), 13% versus 18%, and long-lasting (>1 day) fevers, 23% versus 33%. Co-Administration reduced AEFI risk by 4%-49% with the greatest impact among infants with prior AEFI(s). Fever recurrence risk was proportional to the number of prior fever events: 79% at dose 2 with one prior episode; 44% and 74% at dose 3 with one and two prior episodes, respectively; and 29%, 45% and 60% at dose 4 with one, two and three prior episodes, respectively. Severity was not increased at recurrence and a similar pattern of recurrence risk proportional to the number of prior events was observed for other AEFIs. Conclusions The cumulative risk of AEFI is reduced with concomitant versus separate administration of 4CMenB and routine infant vaccines. Infants with a prior AEFI are at higher risk of the same AEFI at subsequent immunisations, but severity with recurrence is usually not increased. Trials registration number NCT00657709, NCT00847145, NCT00721396 and NCT02712177; Pre-results.
- adverse event
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