Secondary Analysis of the Efficacy and Safety Trial Data of the Tetravalent Dengue Vaccine in Children and Adolescents in Colombia

Abstract

Background: The efficacy of the recombinant, live, attenuated, tetravalent dengue vaccine (CYD-TDV) against virologically-confirmed dengue (VCD) has been documented in a phase 3 trial in Latin America (CYD15, NCT01374516). This is a descriptive secondary analysis of the efficacy and safety of CYD-TDV in participants from Colombia.

Methods: Data from 9740 Colombian participants 9-16 years of age who were randomized 2:1 to receive CYD-TDV or placebo were assessed to describe the vaccine efficacy of CYD-TDV against VCD and severe VCD. Estimation was made of the relative risk (RR) for hospitalized VCD cases and severe hospitalized VCD cases after the first dose of CYD-TDV, as well as a description of the incidence of hospitalized dengue from the start of the study and per year of the study until study completion.

Results: During the active phase of the trial in Colombia, the efficacy of CYD-TDV was 67.5% [95% confidence interval (CI): 58.3-74.7] against symptomatic VCD due to any serotype from injection 1 (month 0) to 25 months postinjection 1. Over 6 years, the RR across all 4 serotypes was 0.166 (95% CI: 0.09-0.29) in hospitalized VCD patients and 0.154 (95% CI: 0.04-0.50) in patients with severe hospitalized VCD.

Conclusions: Analysis of the data from Colombia mimics the efficacy observed in CYD15 during the active surveillance follow-up (25 months), but with a sustained beneficial RR for dengue hospitalizations on the subsequent years of follow-up. In Colombia, where seroprevalence has been demonstrated to be high in several regions of the country, CYD-TDV is a useful tool to consider as part of an integrated control strategy against endemic dengue, a disease with a high economic impact on the health system.

FIGURE 1.

Vaccine efficacy against symptomatic VCD due to any of the 4 serotypes by study phase and dengue serostatus at baseline in Colombia. Serostatus determined by PRNT (measured or imputed) at Month 0. n and N are average numbers from 10 iterations of multiple imputations. Study group classified as randomized (Subjects classified according to the injection assigned at randomization). N indicates total number of subjects selected in sub-cohort; n, number of subjects fulfilling the item listed; N/A, not available.

FIGURE 2.

Risk of dengue hospitalization occurring after Month 0 by time period, in participants who were seropositive (A) or seronegative (B) at baseline in Colombia. Serostatus determined by PRNT (measured or imputed) at Month 0. n and N are average numbers from 10 iterations of multiple imputations. Study group as treated (Subjects classified as CYD-TDV group if received at least 1 injection of CYD-TDV vaccine). Beyond Year 2 Hospital phase means until the end of the study. N indicates total number of subjets selected in sub-cohort; n, number of subjects fulfilling the item listed.

FIGURE 3.

Vaccine efficacy against symptomatic VCD between doses in participants who were seropositive (A) or seronegative (B) at baseline in Colombia. Serostatus Determined By Prnt (Measured Or Imputed) At Month 0 In A Subcohort Of Participants. N And N Are Average Numbers From 10 Iterations Of Multiple Imputations. Study Group Classified As Randomized (Subjects Classified According To The Injection Assigned At Randomization). Eap Indicates End Of The Active Phase; N: Total Number Of Subjets Selected In Sub-Cohort; N, Number Of Subjects Fulfilling The Item Listed.