Vaccine 27 (2009) 4656–4661 Contents lists available at ScienceDirect Vaccine journal homepage: www.elsevier.com/locate/vaccine Observational safety study of febrile convulsion following first dose MMRV vaccination in a managed care setting Steven J. Jacobsen a,b,∗ , Bradley K. Ackerson a,b , Lina S. Sy a,b , Trung N. Tran a,b , Tonia L. Jones a,b , Janis F. Yao a,b , Fagen Xie a,b , T. Craig Cheetham a,b , Patricia Saddier a,b a Kaiser Permanente Southern California, 100 S Los Robles Ave, 2nd Floor, Pasadena, CA 91101, United States b Merck Research Labs, 351 North Sumneytown Pike, UG1D-60, North Wales, PA 19454-25059, United States article info Article history: Received 21 February 2009 Received in revised form 9 May 2009 Accepted 21 May 2009 Available online 9 June 2009 Keywords: Febrile convulsion Vaccination MMRV abstract Background: A combined measles, mumps, rubella, varicella live vaccine (MMRV, Merck and Co., Inc., US) was recently licensed in the US. Pre-licensure clinical trial data showed a significant increase in fever in days 5–12 following MMRV vaccination as compared to the vaccines given separately (MMR+V). This post-licensure retrospective cohort study was undertaken to assess the incidence of febrile convulsion following MMRV. Methods: Children ages 12–60 months who received a first dose of MMRV in February 2006–June 2007 in a managed care organization were included in the study. Subjects were optimally matched on age, sex, and calendar date of vaccination to children who received MMR + V concomitantly in November 2003–January 2006, before MMRV licensure. Potential cases of febrile convulsion were identified through administrative data and adjudicated by expert panel, according to pre-specified criteria. Results: During the 30 days post-vaccination, there were 128 and 94 potential convulsion cases among the 31,298 children in the MMRV and MMR+V cohorts, respectively. After review of available medical charts and adjudication, there were 84 cases of confirmed febrile convulsion, 44 (1.41/1000) and 40 (1.28/1000) in the MMRV and MMR + V cohorts, respectively (RR = 1.10, 95% CI = 0.72, 1.69). In days 5–12 following vaccination, a pre-specified period of interest, the respective numbers were 22 (0.70/1000) and 10 (0.32/1000) (RR = 2.20, 95% CI = 1.04, 4.65). Conclusion: These data suggest that the risk of febrile convulsion is increased in days 5–12 following vacci- nation with MMRV as compared to MMR + V given separately during the same visit, when post-vaccination fever and rash are also increased in clinical trials. While there was no evidence of an increase in the over- all month following vaccination, the elevated risk during this time period should be communicated and needs to be balanced with the potential benefit of a combined vaccine. © 2009 Elsevier Ltd. All rights reserved. 1. Background ProQuad TM , a combined formulation of measles, mumps, rubella, and varicella (MMRV) vaccine that contains components of two Merck vaccines, MMR-II TM (MMR) and VARIVAX TM (V), was approved in the United States (US) in September 2005. Before MMRV was available, MMR and V were usually given concomi- tantly as two separate injections [1]. The new combined vaccine offers several advantages [2]. For parents and providers, the admin- istration of a single vaccine, compared to two, can reduce the time, effort and particularly for the child, attendant anxiety. At the same ∗ Corresponding author at: Department of Research and Evaluation, Kaiser Per- manente Southern California, 100 South Los Robles Avenue, 2nd Floor, Pasadena, CA 91101, United States. Tel.: +1 626 564 3478; fax: +1 626 564 3409. E-mail address: steven.j.jacobsen@kp.org (S.J. Jacobsen). time, however, there is the potential for the combined formula- tion to have a different safety profile compared to the separate vaccines. In pre-licensure clinical trials involving the administration of MMRV to healthy infants and children, most, but not all adverse experiences reported for subjects who received MMRV were comparable to those reported among subjects receiving MMR and varicella vaccines concomitantly (MMR + V) [3]. However, post vaccination fever and measles-like rash were more frequent among recipients of MMRV than recipients of MMR + V, consistent with the higher measles antibody titers among recipients of MMRV [3,4]. Data from pooled MMRV studies [5] showed that the percentages of children with fever were significantly higher during days 0–42 and 5–12 post-vaccination among recipients of MMRV than in recipients of MMR + V. In trials of MMRV versus MMR + V [3,4,6,7], the incidence of febrile convulsions during days 0–42 post-vaccination in recipients of MMRV appeared to be comparable 0264-410X/$ – see front matter © 2009 Elsevier Ltd. All rights reserved. doi:10.1016/j.vaccine.2009.05.056