PC1238: Similar Low Rate of Febrile Convulsions and Comparable Safety Data Reported for Gsk’s Measles-mumps-rubella (MMR) Vaccine versus Merck’s MMR Vaccine in Clinical Trials

Background: The Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices recommends two doses of measles-mumps-rubella (MMR) vaccine, with routine administration of a first dose at 12–15 months of age and a second dose at 4–6 years of age. The first dose of MMR vaccine is administered at an age when susceptible children are at highest risk for febrile convulsions (FCs). Therefore, FC may occur unrelated to vaccination following MMR vaccines. The attributable risk of MMR vaccine‐induced FC is estimated to range between 5.9–8.7/10,000 administered doses. We aimed to summarize the safety data of GSK’s MMR vaccine (GSK-MMR) compared to Merck’s MMR vaccine (M-M-R II), focusing on FCs.

Methods: We reviewed the safety data from six clinical trials (CTs); multi-country, including the United States, comparing the GSK-MMR to the M-M-R II vaccines in ≥12-month-olds. Outcomes of interest were solicited local and general adverse events (AEs), unsolicited AEs and serious AEs (SAEs). Meningism (signs of meningeal irritation) including FCs collected up to 43 days post-vaccination and was categorized as FC and meningism without FC. Onset day, severity and outcome of FCs were evaluated.

Results: Of the six CTs included, four were conducted in 12–15-month-olds, one in 4–6-year-olds and one in ≥7-year-olds. Of 41 cases of meningism including FCs recorded in 39 12–15-month-olds (GSK-MMR: 28 [0.3%] children, M-M-R II: 11 [0.3%]), 36 cases in 34 children were categorized as FC (GSK-MMR: 23 [0.3%] children, M-M-R II: 11 [0.3%]). Across studies, the frequency of FCs was ≤0.4% in both GSK-MMR and M-M-R II groups. The day of onset post-vaccination ranged between 6 and 43 days for GSK-MMR and between 1 and 40 days for M-M-R II. The FC rates within 7–10 days post-vaccination were 5/8386 (5.9/10,000) children for GSK-MMR and 4/3561 (11/10,000) children for M-M-R II. Of the 24 FC cases recorded in the GSK-MMR group, eight were severe. In the M-M-R II group, two of 12 FC cases were severe. All children with FC recovered, in both groups. Of the five cases of meningism including FCs in ≥4-year-olds, one was classified as FC (occurring 38 days post-vaccination in the GSK-MMR group, recovered). The frequencies of solicited/unsolicited local and general AEs and SAEs were comparable between the GSK-MMR and M-M-R II groups across all studies (Table).

Conclusion: The FC rates were low and evenly distributed between GSK-MMR and M-M-R II vaccine groups. The rates of FC between 7–10 days post-vaccination were consistent with the rates reported for both vaccines in the literature, and no specific pattern of FC was identified. Overall, the safety of GSK-MMR vaccine did not differ from the known safety profile of M-M-R II vaccine.

Funding: GlaxoSmithKline Biologicals SA