Efficacy and Long-Term Safety of a Dengue Vaccine in Regions of Endemic Disease
Efficacy and Long-Term Safety of a Dengue Vaccine in Regions of Endemic Disease
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DOI：
10.1056/nejmoa1506223
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发表时间：
2015-09-24
影响因子：
158.5
通讯作者：
Saville, M.
中科院分区：
文献类型：
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作者：
Hadinegoro, S. R.;Arredondo-Garcia, J. L.;Saville, M.
背景候选四价登革热疫苗正在三项临床试验中进行评估，涉及亚太和拉丁美洲国家超过35，000名2至16岁的儿童。我们报告的结果长期随访中期分析和综合疗效analysis.METHODSWe正在评估的发病率住院治疗病毒学证实登革热作为一个替代的安全性终点，在随访期间，在3年至6年的两个3期试验，CYD 14和CYD 15，和2B期试验，CYD 23/57。我们使用CYD 14和CYD 15前25个月的汇总数据估计疫苗有效性。CYD 14和CYD 15的随访数据分别为10，275例受试者中的10，165例（99%）和20，869例受试者中的19，898例（95%）。CYD 23试验纳入CYD 57的4002例受试者中有3203例（80%）的数据可用。在CYD 14，CYD 15和CYD 57试验的第3年，疫苗组22，177名参与者中有65名因病毒学证实的登革热住院治疗，对照组11，089名参与者中有39名。所有参与者中因登革热住院的合并相对风险为0.84（95%置信区间[CI]，0.56至1.24），9岁以下人群为1.58（95% CI，0.83至3.02），9岁或以上人群为0.50（95% CI，0.29至0.86）。在第3年，根据独立数据监测委员会的标准，疫苗组22,177名参与者中有18名因严重登革热住院，对照组11,089名参与者中有6名因严重登革热住院。前25个月内症状性登革热的合并有效率为60.3%（95% CI，55.7至64.5），所有受试者，65.6%（95% CI，60.7至69.9），对于9岁或以上的患者，（95%CI，31.6至55.0）对于那些年龄小于9岁的儿童。结论：尽管在长期随访期间需要仔细监测年龄小于9岁的儿童中第3年因登革热住院的不明原因的较高发病率，接种疫苗组2至16岁儿童的风险低于对照组。（由赛诺菲巴斯德资助; ClinicalTrials.gov编号，NCT 00842530、NCT 01983553、NCT 01373281和NCT 01374516。）
BACKGROUNDA candidate tetravalent dengue vaccine is being assessed in three clinical trials involving more than 35,000 children between the ages of 2 and 16 years in Asian-Pacific and Latin American countries. We report the results of long-term follow-up interim analyses and integrated efficacy analyses.METHODSWe are assessing the incidence of hospitalization for virologically confirmed dengue as a surrogate safety end point during follow-up in years 3 to 6 of two phase 3 trials, CYD14 and CYD15, and a phase 2b trial, CYD23/57. We estimated vaccine efficacy using pooled data from the first 25 months of CYD14 and CYD15.RESULTSFollow-up data were available for 10,165 of 10,275 participants (99%) in CYD14 and 19,898 of 20,869 participants (95%) in CYD15. Data were available for 3203 of the 4002 participants (80%) in the CYD23 trial included in CYD57. During year 3 in the CYD14, CYD15, and CYD57 trials combined, hospitalization for virologically confirmed dengue occurred in 65 of 22,177 participants in the vaccine group and 39 of 11,089 participants in the control group. Pooled relative risks of hospitalization for dengue were 0.84 (95% confidence interval [CI], 0.56 to 1.24) among all participants, 1.58 (95% CI, 0.83 to 3.02) among those under the age of 9 years, and 0.50 (95% CI, 0.29 to 0.86) among those 9 years of age or older. During year 3, hospitalization for severe dengue, as defined by the independent data monitoring committee criteria, occurred in 18 of 22,177 participants in the vaccine group and 6 of 11,089 participants in the control group. Pooled rates of efficacy for symptomatic dengue during the first 25 months were 60.3% (95% CI, 55.7 to 64.5) for all participants, 65.6% (95% CI, 60.7 to 69.9) for those 9 years of age or older, and 44.6% (95% CI, 31.6 to 55.0) for those younger than 9 years of age.CONCLUSIONSAlthough the unexplained higher incidence of hospitalization for dengue in year 3 among children younger than 9 years of age needs to be carefully monitored during long-term follow-up, the risk among children 2 to 16 years of age was lower in the vaccine group than in the control group. (Funded by Sanofi Pasteur; ClinicalTrials.gov numbers, NCT00842530, NCT01983553, NCT01373281, and NCT01374516.)