title: Safety Overview of a Recombinant Live-Attenuated Tetravalent Dengue Vaccine: Pooled Analysis of Data from 18 Clinical Trials.
abstract: A recombinant live attenuated tetravalent dengue vaccine (CYD-TDV) has been shown to be efficacious in preventing virologically-confirmed dengue disease, severe dengue disease and dengue hospitalization in children aged 2-16 years in Asia and Latin America. We analyzed pooled safety data from 18 phase I, II and III clinical trials in which the dengue vaccine was administered to participants aged 2-60 years, including long-term safety follow-up in three efficacy trials. The participants were analyzed according to their age at enrollment. The percentage of participants aged 2-60 years reporting ≥1 solicited injection-site or systemic reactions was slightly higher in the CYD-TDV group than in the placebo group. The most common solicited injection-site reactions were pain. Headache and malaise were the most common solicited systemic reactions. In both groups 0.3% of participants discontinued for safety reasons. The most common unsolicited adverse events were injection-site reactions, gastrointestinal disorders, and infections. Reactogenicity did not increase with successive doses of CYD-TDV. The frequency and nature of SAEs occurring within 28 days of any dose were similar in the CYD-TDV and placebo groups and were common medical conditions that could be expected as a function of age. Baseline dengue virus serostatus did not appear to influence the safety profile. No vaccine-related anaphylactic reactions, neurotropic events or viscerotropic events were reported. In year 3 after dose 1, an imbalance for dengue hospitalization, including for severe dengue, observed in participants aged <9 years in the CYD-TDV group compared with the placebo group was not observed for participants aged ≥9 years. In Year 4, this imbalance in participants aged <9 years was less marked, giving an overall lower risk of dengue hospitalization or severe dengue from dose 1 to Year 4 in the CYD-TDV group. These results have contributed to the definition of the target population for vaccination (≥9 years old) for which CYD-TDV has a satisfactory safety profile. Long-term safety will continue to be monitored in the ongoing follow-up of efficacy trials. Safety and effectiveness in real-life settings will be assessed through post-licensure studies.
authors.affiliation: Sanofi Pasteur, Lyon, France.
authors.forename: Sophia
authors.initials: S
authors.lastname: Gailhardou
authors.affiliation: Sanofi Pasteur, Lyon, France.
authors.forename: Anna
authors.initials: A
authors.lastname: Skipetrova
authors.affiliation: Sanofi Pasteur, Swiftwater, Pennsylvania, United States of America.
authors.forename: Gustavo H
authors.initials: GH
authors.lastname: Dayan
authors.affiliation: Sanofi Pasteur, Swiftwater, Pennsylvania, United States of America.
authors.forename: John
authors.initials: J
authors.lastname: Jezorwski
authors.affiliation: Sanofi Pasteur, Lyon, France.
authors.forename: Melanie
authors.initials: M
authors.lastname: Saville
authors.affiliation: Sanofi Pasteur, Marcy l'Etoile, France.
authors.forename: Diane
authors.initials: D
authors.lastname: Van der Vliet
authors.affiliation: Sanofi Pasteur, Singapore.
authors.forename: T Anh
authors.initials: TA
authors.lastname: Wartel
mesh_terms: D000293:Adolescent; D000328:Adult; D057134:Antibodies, Neutralizing / Q000276:immunology; D000914:Antibodies, Viral / Q000276:immunology; D002648:Child; D002675:Child, Preschool; D003715:Dengue / Q000276:immunology / Q000517:prevention & control* / Q000821:virology; D053059:Dengue Vaccines / Q000008:administration & dosage* / Q000009:adverse effects / Q000235:genetics / Q000276:immunology; D003716:Dengue Virus / Q000235:genetics / Q000276:immunology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D014611:Vaccination; D014613:Vaccines, Attenuated / Q000008:administration & dosage* / Q000009:adverse effects / Q000235:genetics / Q000276:immunology; D055815:Young Adult
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D053059:Dengue Vaccines; D014613:Vaccines, Attenuated