Comparison of intramuscular and subcutaneous administration of a herpes zoster live-attenuated vaccine in adults aged ≥50 years: A randomised non-inferiority clinical trial
Comparison of intramuscular and subcutaneous administration of a herpes zoster live-attenuated vaccine in adults aged ≥50 years: A randomised non-inferiority clinical trial
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DOI：
10.1016/j.vaccine.2014.12.024
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发表时间：
2015-02-04
期刊：
影响因子：
5.5
通讯作者：
Sadorge, Christine
中科院分区：
文献类型：
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作者：
Diez-Domingo, Javier;Weinke, Thomas;Sadorge, Christine
Zostavax（R）是一种水痘带状疱疹病毒（VZV）减毒活疫苗，专门用于预防≥ 50岁人群的HZ和PHN。在主要在美国进行的Zostavax临床开发期间，疫苗通过皮下（SC）途径给药。在欧洲，许多卫生保健专业人员更喜欢通过肌内（IM）途径接种疫苗。这是一项在354名年龄≥ 50岁的受试者中进行的开放标签、随机试验。主要目的是证明IM给药在接种后4周的几何平均滴度（GMT）方面不劣于SC给药，并证明通过糖蛋白酶联免疫吸附试验测定的抗体滴度的几何平均倍数升高（GMFR）可接受。预先规定的非劣效性设定为GMT比率（IM/SC）的95%置信区间（CI）的下限>0.67。IM途径的可接受GMFR预先规定为其95%CI的下限>1.4。使用干扰素-γ酶联免疫斑点（IFN-γ ELISPOT）试验描述VZV免疫应答和安全性是次要目标。两组之间的基线人口统计学特征相当;平均年龄：62.6岁（范围：50.0-90.5岁）。符合主要免疫原性目的（根据方案分析）：GMT比值（IM/SC）：1.05（95% CI：0.93-1.18）; GMFR：2.7（2.4-3.0）。使用IFN-γ ELISPOT的VZV免疫应答在组之间相当。两组间全身不良事件的频率相当。IM给药的注射部位反应频率低于SC给药：分别为红斑（15.9% vs 52.5%）、疼痛（25.6% vs 39.5%）和肿胀（13.6% vs 37.3%）。在≥ 50岁的成人中，Zostavax IM给药引起的免疫应答与SC给药相似，耐受性良好，注射部位反应少于SC给药。(C)2014作者爱思唯尔有限公司出版
Zostavax (R) is a live, attenuated varicella zoster virus (VZV) vaccine developed specifically for the prevention of HZ and PHN in individuals aged >= 50 years. During the clinical development of Zostavax, which was mainly in the US, the vaccine was administrated by the subcutaneous (SC) route. In Europe, many health-care professionals prefer administering vaccines by the intramuscular (IM) route. This was an open-label, randomised trial conducted in 354 subjects aged >= 50 years. The primary objectives were to demonstrate that IM administration is both non-inferior to SC administration in terms of 4-week post-vaccination geometric mean titres (GMTs), and elicits an acceptable geometric mean fold-rise (GMFR) of antibody titres measured by glycoprotein enzyme-linked immunosorbent assay. Pre-specified non-inferiority was set as the lower bound of the 95% confidence interval (CI) of the GMT ratio (IM/SC) being >0.67. An acceptable GMFR for the IM route was pre-specified as the lower bound of its 95% CI being >1.4. Description of the VZV immune response using the interferon-gamma enzyme-linked immunospot (IFN-gamma ELISPOT) assay and of the safety were secondary objectives.Participants were randomised to IM or SC administration (1:1). The baseline demographics were comparable between groups; mean age: 62.6 years (range: 50.0-90.5). The primary immunogenicity objectives were met (per protocol analysis): GMT ratio (IM/SC): 1.05 (95% Cl: 0.93-1.18); GMFR: 2.7 (2.4-3.0). VZV immune response using IFN-gamma ELISPOT were comparable between groups. Frequencies of systemic adverse events were comparable between groups. Injection-site reactions were less frequent with IM than SC route: erythema (15.9% versus 52.5%), pain (25.6% versus 39.5%) and swelling (13.6% versus 37.3%), respectively. In adults aged >= 50 years, IM administration of Zostavax elicited similar immune responses to SC administration and was well tolerated, with fewer injection-site reactions than with SC administration. (C) 2014 The Authors. Published by Elsevier Ltd.