Medical Products Agency, PO Box 26, SE-751 03 Uppsala, Sweden.
BMJ. 2011 Oct 12;343:d5956. doi: 10.1136/bmj.d5956.
OBJECTIVE: To examine the risk of neurological and autoimmune disorders of special interest in people vaccinated against pandemic influenza A (H1N1) with Pandemrix (GlaxoSmithKline, Middlesex, UK) compared with unvaccinated people over 8-10 months. DESIGN: Retrospective cohort study linking individualised data on pandemic vaccinations to an inpatient and specialist database on healthcare utilisation in Stockholm county for follow-up during and after the pandemic period. SETTING: Stockholm county, Sweden. Population All people registered in Stockholm county on 1 October 2009 and who had lived in this region since 1 January 1998; 1,024,019 were vaccinated against H1N1 and 921,005 remained unvaccinated. MAIN OUTCOME MEASURES: Neurological and autoimmune diagnoses according to the European Medicines Agency strategy for monitoring of adverse events of special interest defined using ICD-10 codes for Guillain-Barré syndrome, Bell's palsy, multiple sclerosis, polyneuropathy, anaesthesia or hypoaesthesia, paraesthesia, narcolepsy (added), and autoimmune conditions such as rheumatoid arthritis, inflammatory bowel disease, and type 1 diabetes; and short term mortality according to vaccination status. RESULTS: Excess risks among vaccinated compared with unvaccinated people were of low magnitude for Bell's palsy (hazard ratio 1.25, 95% confidence interval 1.06 to 1.48) and paraesthesia (1.11, 1.00 to 1.23) after adjustment for age, sex, socioeconomic status, and healthcare utilisation. Risks for Guillain-Barré syndrome, multiple sclerosis, type 1 diabetes, and rheumatoid arthritis remained unchanged. The risks of paraesthesia and inflammatory bowel disease among those vaccinated in the early phase (within 45 days from 1 October 2009) of the vaccination campaign were significantly increased; the risk being increased within the first six weeks after vaccination. Those vaccinated in the early phase were at a slightly reduced risk of death than those who were unvaccinated (0.94, 0.91 to 0.98), whereas those vaccinated in the late phase had an overall reduced mortality (0.68, 0.64 to 0.71). These associations could be real or explained, partly or entirely, by residual confounding. CONCLUSIONS: Results for the safety of Pandemrix over 8-10 months of follow-up were reassuring -notably, no change in the risk for Guillain-Barré syndrome, multiple sclerosis, type 1 diabetes, or rheumatoid arthritis. Relative risks were significantly increased for Bell's palsy, paraesthesia, and inflammatory bowel disease after vaccination, predominantly in the early phase of the vaccination campaign. Small numbers of children and adolescents with narcolepsy precluded any meaningful conclusions.
目的:在接种抗大流行性流感 A(H1N1)疫苗的人群与未接种疫苗的人群中,比较接种彭萨可韦(葛兰素史克公司,英国米德尔塞克斯) 8-10 个月后,特殊关注的神经和自身免疫疾病的发病风险。
设计:通过将个体化的大流行性流感疫苗接种数据与斯德哥尔摩县住院患者和专科医生数据库相关联,对斯德哥尔摩县的人群进行前瞻性队列研究,以监测大流行期间和之后的医疗保健利用情况。
地点:瑞典斯德哥尔摩县。人群:2009 年 10 月 1 日在斯德哥尔摩县登记并自 1998 年 1 月 1 日起居住在该地区的所有人员;有 1024019 人接种了 H1N1 疫苗,921005 人未接种疫苗。
主要结局指标:根据欧洲药品管理局监测特殊关注的不良事件的策略,使用国际疾病分类第 10 版编码确定神经和自身免疫诊断,包括吉兰-巴雷综合征、贝尔麻痹、多发性硬化症、多发性神经病、麻醉或感觉减退、感觉异常、发作性睡病(新增)和自身免疫性疾病,如类风湿关节炎、炎症性肠病和 1 型糖尿病;并根据接种状态评估短期死亡率。
结果:调整年龄、性别、社会经济地位和医疗保健利用情况后,与未接种疫苗者相比,接种疫苗者的贝尔麻痹(危险比 1.25,95%置信区间 1.06 至 1.48)和感觉异常(1.11,1.00 至 1.23)的风险较低。吉兰-巴雷综合征、多发性硬化症、1 型糖尿病和类风湿关节炎的风险保持不变。在疫苗接种运动的早期(2009 年 10 月 1 日起 45 天内)接种疫苗者的感觉异常和炎症性肠病风险显著增加;风险在接种后 6 周内增加。与未接种疫苗者相比,早期接种疫苗者的死亡风险略低(0.94,0.91 至 0.98),而晚期接种疫苗者的总体死亡率降低(0.68,0.64 至 0.71)。这些关联可能是真实的,也可能部分或全部是由残余混杂因素造成的。
结论:接种彭萨可韦后 8-10 个月的安全性结果令人放心——特别是,吉兰-巴雷综合征、多发性硬化症、1 型糖尿病或类风湿关节炎的风险没有变化。接种疫苗后,贝尔麻痹、感觉异常和炎症性肠病的相对风险显著增加,主要发生在疫苗接种运动的早期阶段。儿童和青少年发作性睡病的数量较少,无法得出任何有意义的结论。
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