60~69岁接种带状疱疹疫苗效力和成本效益最高

美国疾病预防控制中心免疫实践咨询委员会(ACIP)会议上公布的信息显示，由于带状疱疹疫苗的效力随时间推移而降低，不应对50~59岁的人进行常规接种。

ACIP是在审查默克公司的带状疱疹长期持续性研究的最新数据后提出这一建议的。ACIP发现，在接种后10年，带状疱疹总发生率从4例/1,000人-年增至11例/1,000人-年。在历史对照中观察到的带状疱疹发生率为13例/1,000人-年。



带状疱疹长期持续性研究是带状疱疹预防研究 的8年随访研究。在带状疱疹预防研究中，受试者随机接种默克公司的Zostavax疫苗或安慰剂。结果显示，在60岁以上成人中，该疫苗可显著降低带状疱疹和带状疱疹后遗神经痛(PHN)发生率及带状疱疹疾病负担。

去年进行的一项短期随访研究对超过14,000人的原始队列进行了额外4年随访，结果显示，在接种后6~7年，疫苗效力逐渐降低。在接种后每年对疫苗在所有终点方面的效力进行分析发现，疫苗效力在第1年后降低，并且此后进一步降低。疫苗在带状疱疹发生率和带状疱疹疾病负担方面的效力在接种后第5年仍有统计学显著性，但此后的疫苗效力不确定。

此次亚特兰大会议上公布的长期研究涉及原始队列中近7,000人的12年数据。结果显示疫苗效力随时间推移而不断降低。该研究除了发现带状疱疹年发生率不断增加之外，还发现PHN不断增加，从接种当年的＜1例/1,000人-年增至第10年的1例/1,000人-年。而第10年时，安慰剂受试者和历史对照中的发生率＞2例/1,000人-年。带状疱疹疾病负担(急性疼痛指标)也随时间推移而增加。

综合考虑临床效力和成本，在60~69岁和70~79岁这两个年龄段接种带状疱疹疫苗最有效。在50~59岁接种，每年将可预防20,000例带状疱疹。但在60~69岁接种，每年可预防26,000例，在70~79岁接种，每年可预防21,000例。在PHN病例方面也观察到相似趋势：在50~59岁接种可预防1,000例，在60~69岁接种可预防4,000例，在70~79岁接种可预防8,000例。

在这3个年龄段中，也观察到其他终点(紧急就诊、门诊就诊、住院、住院时间和处方)随时间推移而显著增加。

对来自3个年龄队列的600万人(每个队列各100万接种者和100万未接种者)建立价值评估模型，发现与未接种相比，在50~59岁接种每年可节省1680万美元，在60~69岁接种可节省2430万美元，在70~79岁接种可节省3190万美元。由于较年轻的人可能发生较多的全身反应，因此接种后产生的费用较多。一个计算疫苗、接种操作及治疗局部和全身反应方面的费用的模型发现，在50~59岁接种产生的总费用为1.93亿美元，在60~69岁和70~79岁接种产生的总费用均为1.9亿美元。

在50~59岁队列中，为预防1例带状疱疹、PHN或非PHN并发症的需治数高于60~69岁队列和70~79岁队列(为预防1例带状疱疹，需治数分别为51、38和47；为预防1例PHN，需治数分别为988、247和124)。

ACIP带状疱疹工作组组长Jeff Duchin医生表示，虽然带状疱疹的最大风险出现在较老年的时候，但上述研究结果并非告诉人们不要及早接种带状疱疹疫苗，而是提醒他们注意风险和获益。由于目前尚无有关加强接种带状疱疹疫苗的数据，因此目前仅接种1剂。需把重点放在那些最高危的人身上。

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By: MICHELE G. SULLIVAN, Clinical Neurology News Digital Network

Because efficacy of the shingles vaccine appears to wane over time, it should not routinely be given to people in their 50s, according to information presented at a meeting of the Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices.

"At this time, there is insufficient evidence supporting long-term protection of the vaccine, so if people younger than 60 [years] are vaccinated, they might not be protected when chance of disease is highest," said Dr. Jeff Duchin, chair of the ACIP’s herpes zoster working group. "We will continue to monitor data as they becomes available, but at this point we are reaffirming that vaccination be done in those age 60 [years] and older."
 
The committee made its recommendation after reviewing newly released data from Merck’s Long-Term Persistence Study for shingles. It found that, 10 years after vaccination, the overall incidence rate of shingles had increased from about 4/1,000 person-years to 11/1,000 person-years. The observed incidence rate of shingles in historical controls is about 13 cases/1,000 person-years.

Dr. Janie Parrino, director of vaccine clinical research at Merck Research Laboratories, presented results of the company’s latest study of the vaccine’s extended efficacy. The shingles Long-Term Persistence Study is an 8-year follow-up of the Shingles Prevention Study, in which subjects were randomized to Merck’s Zostavax vaccine or placebo. It showed that the vaccine significantly reduced the incidence of herpes zoster and postherpetic neuralgia (PHN) as well as the shingles burden of illness, in adults older than 60 years.

A short-term follow-up study appeared last year; it added 4 more years of follow-up data on more than 14,000 of the original cohort.

It found a gradual decrease in vaccine efficacy by 6-7 years after vaccination. "Analysis of vaccine efficacy in each year after vaccination for all outcomes showed a decrease after year 1, with a further decline thereafter," the investigators said. "Vaccine efficacy was statistically significant for the incidence of herpes zoster and herpes zoster burden of illness through year 5 after vaccination, but vaccine efficacy is uncertain beyond that point."

The long-term study presented at the Atlanta meeting involved up to 12 years of data on almost 7,000 people in the original cohort. It demonstrated a continuous time-bound waning of efficacy.

In addition to the increasing annual incidence of shingles, the study found an increasing incidence of PHN, from less than 1/1,000 person-years during the year of vaccination to about 1/1,000 person years by year 10. However, the incidence among placebo subjects and historical controls was more than 2/1,000 person years by that time. The shingles burden of illness (a measure of acute pain) also increased as time passed, Dr. Parrino noted.

Taking into account both clinical efficacy and cost, Ismael Ortega-Sanchez, Ph.D., a health economist with the CDC, concluded that the shingles vaccine is most effective when given to people in their 60s and 70s.

Vaccinating from age 50-59 years would prevent about 20,000 shingles cases annually. But vaccinating in the 60s would prevent 26,000 and, in the 70s, 21,000. The trend was similar for cases of PHN: prevention of 1,000 cases for vaccinating in the 50s, 4,000 for vaccinating in the 60s, and 8,000 for vaccinating in the 70s.

Other outcomes – emergency visits, ambulatory visits, hospitalizations, length of hospital stay, and prescriptions – also increased significantly over the 3 decades.

Savings tracked clinical outcomes in a value assessment model of 6 million people: 1 million vaccinated and unvaccinated in each of the three age cohorts.

Compared with not vaccinating, vaccinating those in their 50s would save $16.8 million annually. Vaccinating during the 60s would save about $24.3 million, and during the 70s, $31.9 million.

And, because younger people are likely to have more systemic reactions, they cost more to vaccinate. A model that accounted for the cost of the vaccine, administration, and treating local and systemic reactions, put the total price tag at $193 million for those in their 50s, and $190 million for each of the two older groups.

Finally, the number needed to treat to prevent one case of shingles, PHN, or non-PHN complication case was higher in those in their 50s than in those in their 60s or 70s (one shingles case – 51, 38, and 47 respectively; one PHN case – 988, 247, and 124).

"This isn’t intended to tell people not to get the vaccine early, but to make them aware of the risks and benefits, given that the greatest risk of the disease is later in life," Dr. Duchin said. Since there are no data on booster shingles vaccines, he said "we only have one shot at this and we need to focus our efforts on those at the greatest risk."