JAMA：患者接种带状疱疹疫苗与带状疱疹风险增加没有关系

芝加哥–据7月4日刊《美国医学会杂志》JAMA上的一项研究披露，尽管有些资料提示，接受治疗诸如类风湿性关节炎或牛皮癣等免疫介导性疾病的药物的患者可能会在接受带状疱疹疫苗之后增加其罹患带状疱疹（HZ）的风险，但一项包括了近2万名接种了该疫苗的医疗保险投保人的分析发现，带状疱疹活疫苗与目前接受生物制剂治疗的病人在疫苗接种后不久HZ风险的增加之间没有关系，且它与罹患免疫介导性疾病患者的长期HZ风险的显著下降有关。

根据文章的背景资料：“在2则随机双盲的试验中，一种有活性的减毒疫苗可在50-59岁及60岁或以上的免疫功能正常的人中将HZ的风险分别降低70%及51%。在罹患风湿性疾病及诸如类风湿性关节炎和克隆氏病等免疫介导性疾病中，HZ的风险会增加1.5至2倍。这种增加被归因于基础性的疾病过程及对这些疾病的治疗。”目前，食品与药物管理局（FDA）和其它的组织认为活体HZ疫苗在那些接受某些治疗这些疾病的常用免疫抑制性药物——包括所有的免疫调节型生物制剂及某些非生物性的免疫抑制性药物——的病人中的使用是不当的。文章的作者写道，人们对其安全性的担心是这些人可能会因为疫苗中的病毒株而出现水痘感染。

阿拉巴马大学伯明翰分校的Jie Zhang， Ph.D.及其同事对罹患免疫介导性疾病的患者进行了评估。该回顾性的群组研究通过使用2006年1月直至2009年12月间的医疗保险索赔资料，从而包括了46.3541万名医疗保险受益人，他们的年龄在60岁或以上，并患有类风湿性关节炎、牛皮癣、牛皮癣性关节炎、强直性脊柱炎（一种脊柱的慢性炎症形式），或炎症性肠病。研究人员对在疫苗接种后42天内（出于某种安全性考量）及42天之后的带状疱疹的发生率进行了检测。

在疫苗接种42天以后的阶段中，研究人员对138例HZ进行了观察。在对人口特征、免疫介导性疾病类型、医疗的利用及对生物性和非生物性疾病缓解性抗风湿性药物(DMARDs)及口服糖皮质激素进行控制之后，数据表明，在一个中位随访期为2年的时间中，疫苗接种与HZ的风险降低有关。

文章的作者得出结论：“尽管人们认识到罹患免疫介导性疾病的患者发生HZ的风险会增加，但这则研究和从前的研究显示，这些病人中只有一小部分接种了疫苗，这可能部分是因为对疫苗安全性的担心。我们的数据对目前的HZ疫苗禁用于那些接受生物制剂的病人的建议提出了疑问，并提示有必要开展一项随机对照试验来专门解决在接受生物制剂的病人中的HZ疫苗的安全性和有效性的问题。”

doi:10.1001/jama.2012.7304
PMC:
PMID:

Association Between Vaccination for Herpes Zoster and Risk of Herpes Zoster Infection Among Older Patients With Selected Immune-Mediated Diseases

Jie Zhang, PhD; Fenglong Xie, MS; Elizabeth Delzell, ScD; Lang Chen, PhD; Kevin L. Winthrop, MD, MPH; James D. Lewis, MD, MSCE; Kenneth G. Saag, MD, MSc; John W. Baddley, MD, MSPH; Jeffrey R. Curtis, MD, MS, MPH

Context Based on limited data, the live attenuated herpes zoster (HZ) vaccine is contraindicated in patients taking anti–tumor necrosis factor (anti-TNF) therapies or other biologics commonly used to treat immune-mediated diseases. The safety and effectiveness of the vaccine are unclear for these patients. Objective To examine the association between HZ vaccination and HZ incidence within and beyond 42 days after vaccination in patients with selected immune-mediated diseases and in relation to biologics and other therapies used to treat these conditions. Design, Setting, and Patients Retrospective cohort study of 463 541 Medicare beneficiaries 60 years and older with rheumatoid arthritis, psoriasis, psoriatic arthritis, ankylosing spondylitis, or inflammatory bowel disease using Medicare claims data from January 1, 2006, through December 31, 2009. Main Outcome Measures Herpes zoster incidence rate within 42 days after vaccination (a safety concern) and beyond 42 days; hazard ratios estimated using Cox proportional hazards models for HZ comparing vaccinated vs unvaccinated patients. Results Median duration of follow-up was 2.0 years (interquartile range, 0.8-3.0); 4.0% of patients received HZ vaccine. The overall crude HZ incidence rate was 7.8 cases per 1000 person-years (95% CI, 3.7-16.5) within 42 days after vaccination. The rate among the unvaccinated was 11.6 cases per 1000 person-years (95% CI, 11.4-11.9). Among 633 patients exposed to biologics at the time of vaccination or within the subsequent 42 days, no case of HZ or varicella occurred. After multivariable adjustment, HZ vaccination was associated with a hazard ratio of 0.61 (95% CI, 0.52-0.71) for HZ risk after 42 days. Conclusions Receipt of HZ vaccine was not associated with a short-term increase in HZ incidence among Medicare beneficiaries with selected immune-mediated diseases, including those exposed to biologics. The vaccine was associated with a lower HZ incidence over a median of 2 years of follow-up. Herpes zoster (HZ), caused by the reactivation of latent varicella-zoster virus (VZV), manifests as an acute, painful vesicular rash and is often accompanied by chronic pain or postherpetic neuralgia.1 In the United States, the incidence rate of HZ in the unvaccinated general population 50 years or older is estimated to be 7.0 cases per 1000 person-years.2 A live attenuated vaccine reduces HZ risk by 70% and 51% among immunocompetent individuals 50 to 59 years and 60 years and older in 2 randomized blinded trials, respectively.3 - 4 The Advisory Committee on Immunization Practices (ACIP) recommends a single dose of the zoster vaccine for all people 60 years or older.5 The risk of HZ is elevated by 1.5 to 2 times in patients with rheumatic and immune-mediated diseases such as rheumatoid arthritis (RA) and Crohn disease.6 - 9 This increase has been attributed to both the underlying disease process and treatments for these conditions.6 ,8 - 10 Currently, the Food and Drug Administration (FDA), the ACIP, and the American College of Rheumatology consider the live HZ vaccine to be contraindicated in patients receiving some immunosuppressive medications commonly used to treat these conditions, including all immune-modulating biologic agents; some nonbiologic immunosuppressive medications, such as methotrexate at doses of greater than 0.4 mg per kg per week; and glucocorticoids at prednisone-equivalent doses of 20 mg or more per day.11 - 12 The safety concern is that these individuals may develop varicella infection from the vaccine virus strain. Based on the VZV incubation period,13 - 14 the first 42 days following vaccination was chosen as the primary safety risk window in the Shingles Prevention Study, a randomized blinded trial that preceded the FDA approval of the vaccine.4 In light of the uncertainties regarding the safety and effectiveness of zoster vaccine in patients with immune-mediated diseases, we used administrative claims from US Medicare beneficiaries diagnosed with these diseases to evaluate the association between receipt of zoster vaccine and HZ risk within the first 42 days and up to 3.5 years following vaccination.