From Cipto Mangunkusumo Hospital, University of Indonesia, Jakarta (S.R.H.); Instituto Nacional de Pediatria, Mexico City (J.L.A.-G.); Research Institute for Tropical Medicine, Muntinlupa City, the Philippines (M.R.C.); Caribbean Travel Medicine Clinic, San Juan, Puerto Rico (C.D.); Queen Sirikit National Institute of Child Health (T.C.), Faculty of Tropical Medicine, Mahidol University (K.L.), and Sanofi Pasteur (D.C.) - all in Bangkok, Thailand; Nucleo de Doencas Infecciosas, Universidade Federal do Espirito Santo, Vitoria, ES, Brazil (R.D.); Hospital Kuala Lumpur, Kuala Lumpur, Malaysia (H.I.H.M.I.); Centro de Atencion e Investigacion Medica SAS-CAIMED (H.R.), and Sanofi Pasteur (M.C.) - both in Bogota, Colombia; Organizacion para el Desarrollo y la Investigacion Salud en Honduras (ODIS), Tegucigalpa (D.M.R.-M.); Pasteur Institute in Ho Chi Minh City, Ho Chi Minh City, Vietnam (H.N.T.); Sanofi Pasteur, Singapore, Singapore (A.B., C.F., T.A.W.); Sanofi R&D, Chilly-Mazarin (K.F.), Marcy l'Etoile (R.F., E.P.), and Lyon (S.G., N.J., M.S.) - all in France; Sanofi Pasteur, Swiftwater, PA (F.N.); and Sanofi Pasteur, Montevideo, Uruguay (B.Z.).
N Engl J Med. 2015 Sep 24;373(13):1195-206. doi: 10.1056/NEJMoa1506223. Epub 2015 Jul 27.
A 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.
We 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.
Follow-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.
Although 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.).
候选四价登革热疫苗正在亚洲太平洋和拉丁美洲国家的三项涉及超过 35000 名 2 至 16 岁儿童的临床试验中进行评估。我们报告了长期随访的中期分析和综合疗效分析的结果。
我们正在评估在 CYD14 和 CYD15 的两项 3 期试验以及 CYD23/57 的一项 2b 期试验的第 3 年至第 6 年随访期间，通过病毒学确诊的登革热住院作为替代安全性终点。我们使用 CYD14 和 CYD15 的前 25 个月的数据进行了疫苗疗效的估计。
在 CYD14 中，10275 名参与者中的 10165 名（99%）和 CYD15 中的 20869 名参与者中的 19898 名（95%）可获得随访数据。在包括在 CYD57 中的 4002 名参与者中，有 3203 名（80%）可获得 CYD23 试验的数据。在 CYD14、CYD15 和 CYD57 试验联合的第 3 年期间，疫苗组中有 65 名（22177 名参与者中）和对照组中有 39 名（11089 名参与者中）因经病毒学确诊的登革热住院。所有参与者中，登革热住院的相对风险为 0.84（95%置信区间[CI]，0.56 至 1.24），年龄在 9 岁以下的参与者为 1.58（95%CI，0.83 至 3.02），年龄在 9 岁或以上的参与者为 0.50（95%CI，0.29 至 0.86）。在第 3 年，根据独立数据监测委员会标准，疫苗组中有 18 名（22177 名参与者中）和对照组中有 6 名（11089 名参与者中）因严重登革热住院。在第 25 个月期间，有症状登革热的疫苗疗效率为所有参与者 60.3%（95%CI，55.7 至 64.5），9 岁或以上的参与者为 65.6%（95%CI，60.7 至 69.9），年龄在 9 岁以下的参与者为 44.6%（95%CI，31.6 至 55.0）。
虽然在年龄小于 9 岁的儿童中，第 3 年中登革热住院率的升高原因尚不清楚，但需要在长期随访中仔细监测，2 至 16 岁儿童的风险低于对照组。（由赛诺菲巴斯德公司资助；临床试验.gov 编号，NCT00842530、NCT01983553、NCT01373281 和 NCT01374516。）。
