PMID- 30935742 OWN - NLM STAT- MEDLINE DCOM- 20200916 LR - 20200916 IS - 1873-2518 (Electronic) IS - 0264-410X (Linking) VI - 37 IP - 18 DP - 2019 Apr 24 TI - Safety profile of the adjuvanted recombinant zoster vaccine: Pooled analysis of two large randomised phase 3 trials. PG - 2482-2493 LID - S0264-410X(19)30377-9 [pii] LID - 10.1016/j.vaccine.2019.03.043 [doi] AB - BACKGROUND: The ZOE-50 (NCT01165177) and ZOE-70 (NCT01165229) phase 3 clinical trials showed that the adjuvanted recombinant zoster vaccine (RZV) was >/=90% efficacious in preventing herpes zoster in adults. Here we present a comprehensive overview of the safety data from these studies. METHODS: Adults aged >/=50 (ZOE-50) and >/=70 (ZOE-70) years were randomly vaccinated with RZV or placebo. Safety analyses were performed on the pooled total vaccinated cohort, consisting of participants receiving at least one dose of RZV or placebo. Solicited and unsolicited adverse events (AEs) were collected for 7 and 30 days after each vaccination, respectively. Serious AEs (SAEs) were collected from the first vaccination until 12 months post-last dose. Fatal AEs, vaccination-related SAEs, and potential immune-mediated diseases (pIMDs) were collected during the entire study period. RESULTS: Safety was evaluated in 14,645 RZV and 14,660 placebo recipients. More RZV than placebo recipients reported unsolicited AEs (50.5% versus 32.0%); the difference was driven by transient injection site and solicited systemic reactions that were generally seen in the first week post-vaccination. The occurrence of overall SAEs (RZV: 10.1%; Placebo: 10.4%), fatal AEs (RZV: 4.3%; Placebo: 4.6%), and pIMDs (RZV: 1.2%; Placebo: 1.4%) was balanced between groups. The occurrence of possible exacerbations of pIMDs was rare and similar between groups. Overall, except for the expected local and systemic symptoms, the safety results were comparable between the RZV and Placebo groups irrespective of participant age, gender, or race. CONCLUSIONS: No safety concerns arose, supporting the favorable benefit-risk profile of RZV. CI - Copyright (c) 2019 GlaxoSmithKline Biologicals SA. Published by Elsevier Ltd.. All rights reserved. FAU - Lopez-Fauqued, Marta AU - Lopez-Fauqued M AD - GSK, Wavre, Belgium. Electronic address: marta.x.lopez-fauqed@gsk.com. FAU - Campora, Laura AU - Campora L AD - GSK, Wavre, Belgium. Electronic address: laura.e.campora@gsk.com. FAU - Delannois, Frederique AU - Delannois F AD - GSK, Wavre, Belgium. Electronic address: frederique.x.delannois@gsk.com. FAU - El Idrissi, Mohamed AU - El Idrissi M AD - GSK, Rixensart, Belgium. Electronic address: mohamed.s.elidrissi@gsk.com. FAU - Oostvogels, Lidia AU - Oostvogels L AD - GSK, Wavre, Belgium. Electronic address: cornelia.oostvogels@orange.fr. FAU - De Looze, Ferdinandus J AU - De Looze FJ AD - AusTrials Pty Ltd, Sherwood and School of Medicine, University of Queensland, Brisbane, Queensland, Australia. Electronic address: f.delooze@trialworks.com.au. FAU - Diez-Domingo, Javier AU - Diez-Domingo J AD - Vaccine Research Unit, Fundacion para el Fomento de la Investigacion Sanitaria y Biomedica, Valencia, Spain. Electronic address: jdiezdomingo@gmail.com. FAU - Heineman, Thomas C AU - Heineman TC AD - GSK, King of Prussia, PA, USA. Electronic address: tch3768@gmail.com. FAU - Lal, Himal AU - Lal H AD - GSK, King of Prussia, PA, USA. Electronic address: himallal@yahoo.com. FAU - McElhaney, Janet E AU - McElhaney JE AD - Health Sciences North Research Institute, Sudbury, Ontario, Canada. Electronic address: jmcelhaney@hsnri.ca. FAU - McNeil, Shelly A AU - McNeil SA AD - Canadian Center for Vaccinology, IWK Health Centre and Nova Scotia Health Authority, Dalhousie University, Halifax, Nova Scotia, Canada. Electronic address: Shelly.McNeil@nshealth.ca. FAU - Yeo, Wilfred AU - Yeo W AD - School of Medicine, University of Wollongong, Wollongong, Australia. Electronic address: wilf@uow.edu.au. FAU - Tavares-Da-Silva, Fernanda AU - Tavares-Da-Silva F AD - GSK, Wavre, Belgium. Electronic address: fernanda.tavares@gsk.com. CN - ZOE-50/70 Study Group LA - eng SI - ClinicalTrials.gov/NCT01165177 SI - ClinicalTrials.gov/NCT01165229 PT - Clinical Trial, Phase III PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20190329 PL - Netherlands TA - Vaccine JT - Vaccine JID - 8406899 RN - 0 (Adjuvants, Immunologic) RN - 0 (Herpes Zoster Vaccine) RN - 0 (Vaccines, Synthetic) SB - IM MH - Adjuvants, Immunologic/administration & dosage/adverse effects MH - Aged MH - Cohort Studies MH - Data Interpretation, Statistical MH - Female MH - Herpes Zoster/*prevention & control MH - Herpes Zoster Vaccine/administration & dosage/*adverse effects/genetics MH - Humans MH - Male MH - Middle Aged MH - Vaccines, Synthetic/administration & dosage/*adverse effects OTO - NOTNLM OT - Reactogenicity OT - Safety OT - Vaccine OT - Varicella-zoster virus FIR - Ahonen, Anitta IR - Ahonen A IRAD- University of Tampere, Jarvenpaa Vaccine Clinic, Finland. FIR - Avelino-Silva, Thiago Junquera IR - Avelino-Silva TJ IRAD- University of Sao Paulo Medical School, Brazil. FIR - Barba-Gomez, Jose Fernando IR - Barba-Gomez JF IRAD- Instituto Dermatologico de Jalisco, Mexico. FIR - Berglund, Johan IR - Berglund J IRAD- Blekinge Institute of Technology, Sweden. FIR - Cuixart, Carlos Brotons IR - Cuixart CB IRAD- EAP Sardenya, Spain. FIR - Caso, Covadonga IR - Caso C IRAD- Hospital Clinico San Carlos, Spain. FIR - Chlibek, Roman IR - Chlibek R IRAD- University of Defence, Faculty of Military Health Sciences, Czech Republic. FIR - Choi, Won Suk IR - Choi WS IRAD- Korea University College of Medicine, Republic of Korea. FIR - Cunningham, Anthony L IR - Cunningham AL IRAD- Westmead Institute for Medical Research, University of Sydney, Australia. FIR - Desole, Maria Guiseppina IR - Desole MG IRAD- Servizio di Igiene Pubblica, Italy. FIR - Eizenberg, Peter IR - Eizenberg P IRAD- Doctors of Ivanhoe, Australia. FIR - Esen, Meral IR - Esen M IRAD- Institut fur Tropenmedizin, University Clinic of Tubingen, Germany. FIR - Espie, Emmanuelle IR - Espie E IRAD- GSK, Belgium. FIR - Gervais, Pierre IR - Gervais P IRAD- Q&T Research Sherbrooke, Canada. FIR - Ghesquiere, Wayne IR - Ghesquiere W IRAD- University of British Columbia, Canada. FIR - Godeaux, Olivier IR - Godeaux O IRAD- GSK, Belgium, during the conduct of the ZOE-50/70 trials, Belgium. FIR - Gorfinkel, Iris IR - Gorfinkel I IRAD- York University, Canada. FIR - Hui, David Shu Cheong IR - Hui DSC IRAD- Prince of Wales Hospital, Hong Kong. FIR - Hwang, Shinn-Jang IR - Hwang SJ IRAD- Taipei Veterans General Hospital and National Yang Ming University School of Medicine, Taiwan. FIR - Korhonen, Tiina IR - Korhonen T IRAD- Vaccine Research Centre, University of Tampere Medical School, Tampere, Finland. FIR - Kovac, Martina IR - Kovac M IRAD- GSK, USA. FIR - Ledent, Edouard IR - Ledent E IRAD- GSK, Belgium. FIR - Leung, Edward IR - Leung E IRAD- Hong Kong Association of Gerontology, Hong Kong. FIR - Levin, Myron J IR - Levin MJ IRAD- University of Colorado Anschutz Medical Campus, USA. FIR - Perez, Silvia Narejos IR - Perez SN IRAD- CAP Centelles, Spain. FIR - Neto, Jose Luiz IR - Neto JL IRAD- Instituto A. Z. de Pesquisa e Ensino, Brazil. FIR - Pauksens, Karlis IR - Pauksens K IRAD- Uppsala University Hospital, Sweden. FIR - Poder, Airi IR - Poder A IRAD- Kliiniliste Uuringute Keskus, Estonia. FIR - de la Pinta, Maria Luisa Rodriguez IR - de la Pinta MLR IRAD- Hospital Puerta de Hierro, Spain. FIR - Rombo, Lars IR - Rombo L IRAD- Uppsala University, Sweden. FIR - Schwarz, Tino F IR - Schwarz TF IRAD- Standort Juliusspital, Germany. FIR - Smetana, Jan IR - Smetana J IRAD- University of Defence, Faculty of Military Health Sciences, Czech Republic. FIR - Staniscia, Tommaso IR - Staniscia T IRAD- University G. d'Annunzio of Chieti-Pescara, Italy. FIR - Tinoco, Juan Carlos IR - Tinoco JC IRAD- Hospital General de Durango, Mexico. FIR - Toma, Azhar IR - Toma A IRAD- Manna Research, Canada. FIR - Vastiau, Ilse IR - Vastiau I IRAD- GSK, Belgium. FIR - Vesikari, Timo IR - Vesikari T IRAD- University of Tampere, Finland. FIR - Volpi, Antonio IR - Volpi A IRAD- A.O. Univesitaria Policlinico Tor Vergata, Italy. FIR - Watanabe, Daisuke IR - Watanabe D IRAD- Kobe University Graduate School of Medicine, Japan. FIR - Weckx, Lily Yin IR - Weckx LY IRAD- Federal University of Sao Paulo, Brazil. FIR - Zahaf, Toufik IR - Zahaf T IRAD- GSK, Belgium. EDAT- 2019/04/03 06:00 MHDA- 2020/09/17 06:00 CRDT- 2019/04/03 06:00 PHST- 2018/11/15 00:00 [received] PHST- 2019/03/14 00:00 [revised] PHST- 2019/03/20 00:00 [accepted] PHST- 2019/04/03 06:00 [pubmed] PHST- 2020/09/17 06:00 [medline] PHST- 2019/04/03 06:00 [entrez] AID - S0264-410X(19)30377-9 [pii] AID - 10.1016/j.vaccine.2019.03.043 [doi] PST - ppublish SO - Vaccine. 2019 Apr 24;37(18):2482-2493. doi: 10.1016/j.vaccine.2019.03.043. Epub 2019 Mar 29.