带状疱疹重组疫苗对自体造血干细胞移植后带状疱疹发病率的影响：一项随机临床试验。
Effect of Recombinant Zoster Vaccine on Incidence of Herpes Zoster After Autologous Stem Cell Transplantation: A Randomized Clinical Trial.
机构信息
GlaxoSmithKline, Wavre, Belgium.
Hospital Universitario 12 de Octubre, Madrid, Spain.
出版信息
JAMA. 2019 Jul 9;322(2):123-133. doi: 10.1001/jama.2019.9053.
IMPORTANCE
Herpes zoster, a frequent complication following autologous hematopoietic stem cell transplantation (HSCT), is associated with significant morbidity. A nonlive adjuvanted recombinant zoster vaccine has been developed to prevent posttransplantation zoster.
OBJECTIVE
To assess the efficacy and adverse event profile of the recombinant zoster vaccine in immunocompromised autologous HSCT recipients.
DESIGN, SETTING, AND PARTICIPANTS: Phase 3, randomized, observer-blinded study conducted in 167 centers in 28 countries between July 13, 2012, and February 1, 2017, among 1846 patients aged 18 years or older who had undergone recent autologous HSCT.
INTERVENTIONS
Participants were randomized to receive 2 doses of either recombinant zoster vaccine (n = 922) or placebo (n = 924) administered into the deltoid muscle; the first dose was given 50 to 70 days after transplantation and the second dose 1 to 2 months thereafter.
MAIN OUTCOMES AND MEASURES
The primary end point was occurrence of confirmed herpes zoster cases.
RESULTS
Among 1846 autologous HSCT recipients (mean age, 55 years; 688 [37%] women) who received 1 vaccine or placebo dose, 1735 (94%) received a second dose and 1366 (74%) completed the study. During the 21-month median follow-up, at least 1 herpes zoster episode was confirmed in 49 vaccine and 135 placebo recipients (incidence, 30 and 94 per 1000 person-years, respectively), an incidence rate ratio (IRR) of 0.32 (95% CI, 0.22-0.44; P < .001), equivalent to 68.2% vaccine efficacy. Of 8 secondary end points, 3 showed significant reductions in incidence of postherpetic neuralgia (vaccine, n=1; placebo, n=9; IRR, 0.1; 95% CI, 0.00-0.78; P = .02) and of other prespecified herpes zoster-related complications (vaccine, n=3; placebo, n=13; IRR, 0.22; 95% CI, 0.04-0.81; P = .02) and in duration of severe worst herpes zoster-associated pain (vaccine, 892.0 days; placebo, 6275.0 days; hazard ratio, 0.62; 95% CI, 0.42-0.89; P = .01). Five secondary objectives were descriptive. Injection site reactions were recorded in 86% of vaccine and 10% of placebo recipients, of which pain was the most common, occurring in 84% of vaccine recipients (grade 3: 11%). Unsolicited and serious adverse events, potentially immune-mediated diseases, and underlying disease relapses were similar between groups at all time points.
CONCLUSIONS AND RELEVANCE
Among adults who had undergone autologous HSCT, a 2-dose course of recombinant zoster vaccine compared with placebo significantly reduced the incidence of herpes zoster over a median follow-up of 21 months.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT01610414.
重要性：带状疱疹是自体造血干细胞移植（HSCT）后的常见并发症，与明显的发病率相关。为了预防移植后带状疱疹，已经开发出一种非活佐剂重组带状疱疹疫苗。
目的：评估重组带状疱疹疫苗在免疫功能低下的自体 HSCT 受者中的疗效和不良事件谱。
设计、地点和参与者：这是一项在 28 个国家的 167 个中心进行的 3 期、随机、观察者盲法研究，于 2012 年 7 月 13 日至 2017 年 2 月 1 日期间入组了 1846 例年龄在 18 岁或以上且近期接受过自体 HSCT 的患者。
干预措施：参与者被随机分配接受 2 剂重组带状疱疹疫苗（n=922）或安慰剂（n=924），肌肉注射于三角肌；第一剂在移植后 50-70 天给予，第二剂在 1-2 个月后给予。
主要终点和测量指标：主要终点是确诊的带状疱疹病例发生情况。
结果：在 1846 例接受 1 剂或安慰剂的自体 HSCT 受者（平均年龄 55 岁；688[37%]为女性）中，1735 例（94%）接受了第二剂，1366 例（74%）完成了研究。在 21 个月的中位随访期间，至少有 1 例带状疱疹发作的情况在 49 例疫苗组和 135 例安慰剂组中得到确认（发生率分别为每 1000 人年 30 和 94 例，发病率比为 0.32，95%CI，0.22-0.44；P<0.001），疫苗的效力为 68.2%。在 8 个次要终点中，有 3 个与带状疱疹后神经痛（疫苗组 n=1；安慰剂组 n=9；发病率比 0.1；95%CI，0.00-0.78；P=0.02）、其他特定的带状疱疹相关并发症（疫苗组 n=3；安慰剂组 n=13；发病率比 0.22；95%CI，0.04-0.81；P=0.02）和严重的最严重带状疱疹相关疼痛的持续时间（疫苗组 892.0 天；安慰剂组 6275.0 天；风险比 0.62；95%CI，0.42-0.89；P=0.01）显著降低相关。其他 5 个次要目标为描述性的。疫苗组 86%的患者和安慰剂组 10%的患者出现注射部位反应，其中疼痛最常见，疫苗组中有 84%的患者出现（3 级：11%）。在所有时间点，疫苗组和安慰剂组的注射部位反应、不良事件、潜在免疫介导性疾病和基础疾病复发均相似。
结论和相关性：在接受自体 HSCT 的成年人中，与安慰剂相比，2 剂重组带状疱疹疫苗显著降低了中位数为 21 个月的带状疱疹发病率。
试验注册：ClinicalTrials.gov 标识符：NCT01610414。
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