[HTML][HTML] Four-year efficacy of RTS, S/AS01E and its interaction with malaria exposure

A Olotu, G Fegan, J Wambua… - … England Journal of …, 2013 - Mass Medical Soc
A Olotu, G Fegan, J Wambua, G Nyangweso, KO Awuondo, A Leach, M Lievens…
New England Journal of Medicine, 2013Mass Medical Soc
Background The candidate malaria vaccine RTS, S/AS01E has entered phase 3 trials, but
data on long-term outcomes are limited. Methods For 4 years, we followed children who had
been randomly assigned, at 5 to 17 months of age, to receive three doses of RTS, S/AS01E
vaccine (223 children) or rabies vaccine (224 controls). The end point was clinical malaria
(temperature of≥ 37.5° C and Plasmodium falciparum parasitemia density of> 2500
parasites per cubic millimeter). Each child's exposure to malaria was estimated with the use …
Background
The candidate malaria vaccine RTS,S/AS01E has entered phase 3 trials, but data on long-term outcomes are limited.
Methods
For 4 years, we followed children who had been randomly assigned, at 5 to 17 months of age, to receive three doses of RTS,S/AS01E vaccine (223 children) or rabies vaccine (224 controls). The end point was clinical malaria (temperature of ≥37.5°C and Plasmodium falciparum parasitemia density of >2500 parasites per cubic millimeter). Each child's exposure to malaria was estimated with the use of the distance-weighted local prevalence of malaria.
Results
Over a period of 4 years, 118 of 223 children who received the RTS,S/AS01E vaccine and 138 of 224 of the controls had at least 1 episode of clinical malaria. Vaccine efficacies in the intention-to-treat and per-protocol analyses were 29.9% (95% confidence interval [CI], 10.3 to 45.3; P=0.005) and 32.1% (95% CI, 11.6 to 47.8; P=0.004), respectively, calculated by Cox regression. Multiple episodes were common, with 551 and 618 malarial episodes in the RTS,S/AS01E and control groups, respectively; vaccine efficacies in the intention-to-treat and per-protocol analyses were 16.8% (95% CI, −8.6 to 36.3; P=0.18) and 24.3% (95% CI, 1.9 to 41.6; P=0.04), respectively, calculated by the Andersen–Gill extension of the Cox model. For every 100 vaccinated children, 65 cases of clinical malaria were averted. Vaccine efficacy declined over time (P=0.004) and with increasing exposure to malaria (P=0.001) in the per-protocol analysis. Vaccine efficacy was 43.6% (95% CI, 15.5 to 62.3) in the first year but was −0.4% (95% CI, −32.1 to 45.3) in the fourth year. Among children with a malaria-exposure index that was average or lower than average, the vaccine efficacy was 45.1% (95% CI, 11.3 to 66.0), but among children with a malaria-exposure index that was higher than average it was 15.9% (95% CI, −11.0 to 36.4).
Conclusions
The efficacy of RTS,S/AS01E vaccine over the 4-year period was 16.8%. Efficacy declined over time and with increasing malaria exposure. (Funded by the PATH Malaria Vaccine Initiative and Wellcome Trust; ClinicalTrials.gov number, NCT00872963.)
The New England Journal Of Medicine