認識帶狀疱疹及預防方式 · 2013-10-01 · HIGH CONTAGIOUS •One study showed a 75%...

桃園縣藥師公會藥師持續教育訓練

認識帶狀疱疹及預防方式

台大醫院家庭醫學部主治醫師台大醫學院一般醫學科臨床助理教授

蔡詩力

帶狀皰疹的病原體

Varicella Zoster Virus, VZV (水痘病毒)的入侵

初識VZV --水痘

• 流行季節在冬季及早春

• 好發年齡:60％個案為3-9歲

• 90％以上民眾在15歲以前曾經感染過水痘

• 絕大部份病患都不會引起併發症

• 併發症的高危險群 : 大於20歲病患、免疫功能不全病患

•3

水痘的治療

• 鑑別 : 一般 VS 重症疑慮

• 一般處置

症狀治療

呼吸道、皮膚、營養、疼痛、情緒…

• 重症疑慮族群?

• 重症疑慮處置

IV Acyclovir -- VZV

Steroid – cytokine storm

Vital sign…

HIGH CONTAGIOUS

• One study showed a 75% secondary attack rate with chickenpox in susceptible household contacts.[1]

• More than 90% of adults have been infected although many will not remember having it or may have had subclinical infection.

• Most adults in Australia are at risk of developing herpes zoster.

• Studies have shown that about 1/3 of the population will experience herpes zoster during the course of their lifetime with the incidence increasing particularly after the age of 60 years.[2]

Varicella-Zoster Virus (VZV): Immune Response

• Both structural and regulatory

proteins of VZV are recognized

during primary varicella infection

by T lymphocytes.1

• Cell-mediated (T-cell) immunity is

required to maintain the balance

between host and latent VZV.1

• Cell-mediated immunity is more

important than humoral immunity

in recovery from varicella.2

• Immunity persists following

disease.2

• T-cell immunity is also aging when

aging…

•1. Gershon AA et al. In: Vaccines. 5th ed. Elsevier; 2008:915–958.

•2. Straus SE et al. In: Freedberg IM et al, eds. Fitzpatrick’s Dermatology in General Medicine. 5th ed. Vol 2. McGraw-Hill; 1999:2427–2450.

Host Factors in Varicella-Zoster Virus (VZV)

Latency and Reactivation

•Reprinted with permission from Arvin A. N Engl J Med. 2005;352:2266–2267. Copyright © 2005 Massachusetts Medical Society. All rights reserved.

•VZ

V M

em

ory

T C

ells

•Age

•Varicella infection

•Herpes zoster

•Zoster threshold

•Exogenous •varicella exposure

•Silent reactivation?

•Zoster vaccination

水痘痊癒後，VZV跑那兒去…

1. Opstelten et al. Herpes zoster and post herpetic neuralgia: incidence and risk indicators using a general practice research database. Family Practice. 19:5;471-475. 2002. 2. CDC Immunization. Immunization: Shingles

Vaccine. www.cdc.gov/vaccines. Accessed 14 Feb 2013. 3. National Institute of Aging. Age Page: Shingles. www.nia.nih.gov/health/publication/shingles. Accessed 14 Feb 2013. 4. ShinglesInfo.com – FAQ. Accessed May 2013.

http://www.shinglesinfo.com/shinglesinfo/shingles-in-depth/questions-about-shingles.jsp#4

水痘病毒被身體免疫壓制

潛伏在背根神經節

病毒沿著神經跑到體表

Chickenpox (VZV) rash

Skin

脊隨

T-cell免疫力下降會發生的事!!!

http://www.nia.nih.gov/health/publication/shingles. Accessed 14 Feb 2013

http://www.shinglesinfo.com/shinglesinfo/shingles-in-depth/questions-about-shingles.jsp









Case I

• 38 歲男性

• 北部某醫學中心婦產科主治醫師

• 小學五年級時，水痘發作

• 高三寒假時，皮蛇發作

症狀 -- 疼痛、注意力不集中、焦慮、失眠…

9

T-cell免疫力下降還會發生什麼事…

你得過帶狀疱疹嗎？

• >50歲都可能會得帶狀疱疹

• 帶狀疱疹(Herpes zoster; HZ)(俗稱皮蛇)是VZV(水痘-帶狀疱疹病毒)再度活化的表現

• 症狀表現: 延著皮節分佈的單側性、疼痛性、水泡性皮疹

• 疼痛症狀可能會發生於感染的前驅期、急性發疹期、以及疱疹後期。

• 曾有報告指出，在急性發疹期間，高達90%會發生局部神經疼痛

• 疼痛期: 可長達兩年




Dorsal root

ganglion

VZV establishes

latency in the

dorsal root ganglion

VZV moves along

the sensory nerve

to the dorsal root

ganglion


Skin

Spinal cord











•帶狀疱疹的發生率台灣：2000-2006

•JHI. et.al. Acta Derm Venereol. 2009. 89: 612-616

年齡－重要因素

• 年齡是罹患帶狀疱疹最重要的一項因素

• 超過50歲後，罹患帶狀疱疹的風險及嚴重性會大幅增加，這是由於免疫力會隨著年齡增長而降低的緣故

- 到了85歲，約有50%的人會出現至少一次的帶狀疱疹

過去50年來，老年人的

數量已增加一倍；在接

下來的50年，老年人增

加的數量將更多

有越來越多的人將達到

易罹患帶狀疱疹的年齡

隨著年齡增長,罹患帶狀

疱疹的風險越高

1. CDC. MMWR. Prevention of Herpes Zoster: Recommendations of the Advisory Committee on Immunization Practices. 2008; 57:1-30. 2. Shinglesinfo.com. FAQ. www.shinglesinfo.com/shinglesinfo/shingles-in-depth/questions-about-shingles.jsp Accessed 28 May

2013 3. Schmader, K. Herpes Zoster in Older Adults. Aging and Infectious Diseases. CID. 2001:32 1481-1486 4. Oxman, M.N. A Vaccine to Prevent Herpes Zoster and Postherpetic Neuralgia in Older Adults. N Engl J Med 2005 352:22, 2271-84. 5. National

Institute of Aging. Age Page: Shingles. www.nia.nih.gov/health/publication/shingles. accessed 14 Feb 2013. 6. Population Division, DESA, United Nations. World Population Ageing: 1950-2050. Chapter II:11. 7. WHO. Ageing and Life Course. 2013

http://www.who.int/ageing/en/ Accessed on 29 May 2013.










http://www.nia.nih.gov/health/publication/shingles. accessed 14 Feb 2013

http://www.who.int/ageing/en/

全世界罹患帶狀疱疹的年齡分布

0

2

4

6

8

10

12

14

16

18

20

0 10 20 30 40 50 60 70 80 90An

nu

al

Incid

en

ce

(pe

r 1,0

00 p

ers

on

-ye

ars

)

Age

Hope-Simpson (UK) Brisson (UK)

Gonzalez (France) Ultsch (Germany)

Insinga (US) Yawn (US)

Stein (Australia) Brisson (Canada)

Jih (Taiwan) Choi (South Korea)

1. Brisson M et al. Epidemiol Infect. 2001;127:305–314. 2. Choi WS et al. J Clin Virol. 2010;47:325–329. 3. Gonzalez Chiappe S et al. Vaccine. 2010;28:7933–7938. 4. Hope-Simpson RE. Proc R Soc Med. 1965;58:9–20. 5 Insinga RP et al. J Gen Intern Med.

2005;20:748–753. 6. Jih JS et al. Acta Derm Venereol. 2009;89:612–616. 7. Stein AN et al. Vaccine. 2009;27:520–529. 8. Ultsch B et al. BMC Infect Dis. 2011;11:173. 9. Yawn BP et al. Mayo Clin Proc. 2007;82:1341–1349.10. Shinglesinfo.com. FAQ.

www.shinglesinfo.com/shinglesinfo/shingles-in-depth/questions-about-shingles.jsp Accessed 28 May 2013 11. Population Division, DESA, United Nations. World Population Ageing: 1950-2050. Chapter II:11. 12. Schmader, K. Herpes Zoster in Older Adults. Aging

and Infectious Diseases. CID. 2001:32 1481-1486 13. Oxman, M.N. A Vaccine to Prevent Herpes Zoster and Postherpetic Neuralgia in Older Adults. N Engl J Med 2005 352:22, 2271-84.

Worldwide Shingles by Age

病毒性疫苗

病毒性疾病疫苗成分使用者麻疹減毒兒童腮腺炎減毒兒童德國麻疹減毒兒童水痘減毒兒童流行性感冒去活化醫護年長 B型肝炎次蛋白新生兒高危險群 A型肝炎去活化兒童流行區腺病毒減毒軍事人員黃熱病減毒軍事人員旅行者狂犬病去活化獸醫處理動物天花痘病毒已不需要日本腦炎去活化旅行者小兒麻痺去活化-沙克兒童減毒-沙賓兒童

減毒疫苗製作概念

18

帶狀疱疹的徵兆及症狀

• 起初的徵兆並不明顯，症狀往往是發癢、疼痛及刺痛

• 幾天之後會出現水泡紅疹，通常會出現在身體或臉部的單側

• 紅疹的出現通常伴隨：

- 焦慮

- 類流感症狀

- 從輕微到嚴重的疼痛，包含：

•發癢、灼熱感或刺痛

•抽痛

• 96%罹患帶狀疱疹的人會感到疼痛

• 45%每天都感到疼痛

• 42%形容此疼痛感為”可怕的”或”難忍受的”

1. Goh, CL. A retrospective study of the clinical presentation and outcome of herpes zoster in a tertiary dermatology outpatient referral clinic. International Journal of Dermatology. 1997, 36, 667-672. 2. Schmader, K. Herpes Zoster in Older Adults. Aging and

Infectious Diseases. CID. 2001:32 1481-1486 3. Oxman MN. Clinical manifestations of herpes zoster. In: Arvin AM, Gershon AA, eds. Varicella-Zoster Virus Virology and Clinical Management. 2000; Cambridge Press: pp.246-75. 4. Stankus et al. Management of

Herpes Zoster (Shingles) and Postherpetic Neuralgia. Am Fam Physician. April 15;61(8):2437-2444 5. Katz, J. Acute Pain in Herpes Zoster and Its Impact on Health-Related Quality of Life. Clinical Infectious Diseases. 2005. 39:342-8

© Phototake. Reprinted with permission.

帶狀皰疹疼痛的原因

我們如何感到疼痛

•大腦

•脊髓背側角

•痛覺受器

•神經連結

• 組織受損時會對痛覺受器

造成刺激。

• 痛覺受器會將訊號傳遞至

大腦，從而使身體產生疼

痛的感覺。

• 疼痛的程度取決於受到刺

激之痛覺受器的數目。 •疼痛的訊息從受傷部位的周邊神經

中的痛覺受器，傳到脊髓神經，再

傳達到大腦感受到疼痛的訊息。

疼痛的病理機轉

帶狀疱疹如何作怪?




水痘病毒被身體免疫壓制

潛伏在背根神經節

病毒沿著神經跑到體表


Skin

脊隨











Total pain

physical

↓

Psychological → Total pain ← Social

↑

Spiritual

26

疼痛評估工具 (1)

•哭笑臉譜疼痛評估表 (Facial Affective Scale)

•0

cm

•10

cm

•視覺同化評估表 (Visual Analogue Scale, VAS)

27

疼痛評估工具 (2)

•疼痛分數評估表 (Numeric rating Scale)

軀體性痛(somatic pain)

• 由於皮膚、軟組織、骨骼傷害而造成的疼痛

• 病人會感到持續的刺痛、銳痛或壓痛,有固定疼痛部位,與體神經分佈有關

臟器痛(visceral pain)

• 由於臟器直接刺激痛覺神經而造成的

• 疼痛部位一般顯較為糢糊,常合併轉移痛(referred pain)

• 若來自中空的器官阻塞,表現為間歇性的鈍痛或絞痛;若來自實質器官的包膜或腸繫膜,則表現為銳痛或脹痛

神經病變性痛(neuropathic pain)

• 由於周邊神經受損或長期受壓迫所造成

• 常見造成原因:腫瘤浸潤或侵犯神經叢、帶狀庖疹感染、手術傷害神經

• 病人會覺得尖銳痛、燒灼痛或刺痛

• 對傳統止痛藥的反應不佳,但部份抗憂鬱劑(antidepression)或抗痙攣藥(anticonvulsant)可能會有幫助

Case II

• 77歲女性，國小教師退休

• 移民台北三個月…

• 感冒症狀一天

• 第二天，右耳癢+痛，女兒發現嘴歪歪

• 第三天，右耳出現小水泡+微微紅疹

• 第四天住院治療

31

帶狀疱疹引起的疼痛對日常活動的影響

0

10

20

30

40

50

60

70

80

90

100

0 1 2 3 4 5 6 7 8 9 10

Worst pain score

Pa

tie

nts

re

po

rtin

g in

terf

ere

nc

e (

%)

General activity

Work

Sleep

Enjoyment of life

1. Adapted from Lydick E, Epstein RS, et al. Neurology; 1995;45 (suppl 8):S52

帶狀疱疹的併發症

• 4位病人當中就有1位會得到1種或多種併發症

• 對某些人來說，帶狀疱疹會導致長期的神經疼痛，稱為帶狀疱疹後神經痛（Postherpetic Neuralgia, PHN)

其它的併發症包含：

• 帶狀疱疹病毒眼症(Zoster opthalmicus)

– 罹患帶狀疱疹的病人有10-25%會發生

– 在這些人當中，50-72%的病人會得到嚴重的眼疾及視力退化

• 皮膚細菌感染

• 肌肉無力

• 留下疤痕

• 聽力損失

1. Lang et al. Stop Shingles in its tracks. Journal Fam Pract. Oct 2009. 58;10:531-534 2. Yawn BP et al. Mayo Clin Proc. 2007;82:1341–1349. 3. CDC Harpaz, R. Prevention of Herpes Zoster. Recommendations of the ACIP. MMWR. 2008: 57: 1-30. 4. Oxman MN.

Clinical manifestations of herpes zoster. In: Arvin AM, Gershon AA, eds. Varicella-Zoster Virus Virology and Clinical Management. 2000; Cambridge Press: pp.246-75. 5. Pavan-Langston, D. Ophthalmic zoster: Varicella-zoster virus. Virology and Clinical

Management. 2000. 276-298. 6. National Institute of Aging. Age Page: Shingles. www.nia.nih.gov/health/publication/shingles. Accessed 14 Feb 2013. 7. US National Library of Medicine. PubMed Health. Shingles. Accessed May 2013. Available at:

http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0001861/


http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0001861/

1. Kost R et al. N Engl J Med. 1996; 355:32-42.

Pati

en

ts r

ep

ort

ing

pain

(%

)

Age (years)

0

100

80

60

40

20

0-19

20-29

30-39

40-49

50-59

60-69

≥79

>1 yr

<1 mo

6 - 12 mo

1 - 6 mo

帶狀疱疹引起疼痛的程度及持續性與年齡層的的關聯性

社會層面

• 退縮

• 孤立

• 社交聚會次數減少

• 喪失獨立性

• 社會角色的改變

帶狀疱疹及帶狀疱疹後神經痛(PHN) 對健康的衝擊

生理層面

• 疲勞

• 缺乏食慾

• 體重減輕

• 行動力下降

• 體能活動不足

• 失眠

心理層面

• 憂鬱

• 焦慮

• 情緒壓力

• 注意力無法集中

• 恐懼感

1. Johnson, R. The impact of herpes zoster and postherpetic neuralgia on quality of life. BMC Medicine. 2010. 8:37. 2. Katz, J. Acute Pain in Herpes Zoster and Its Impact on Health-Related Quality of Life. Clinical Infectious Diseases. 2005.

39:342-8

功能層面

• 穿著、洗澡、飲食、行動

• 旅行、烹飪、家務、購物

帶狀疱疹的治療

• 帶狀疱疹的治療：

– 通常需要全方位的治療

– 通常是複雜的

– 所費不貲

• 帶狀疱疹的抗病毒治療應在紅疹出現後72小時內開始，但病患通常會拖過72小時後才就醫

1. Gnann JW et al. N Engl J Med. 2002;347:340–346. 2. Johnson, R. The impact of herpes zoster and postherpetic neuralgia on quality of life. BMC Medicine. 2010. 8:37 3. Goh, CL. A retrospective study of the clinical presentation and outcome of herpes zoster in

a tertiary dermatology outpatient referral clinic. International Journal of Dermatology. 1997, 36, 667-672. 4. Watson, CP. The prognosis with postherpetic neuralgia. 1991. 46 (2) 195-199. 5. CDC. Prevention of Herpes Zoster: Recommendations of the ACIP. MMWR.

2008: 57: 1-30.

雖然帶狀疱疹後神經痛會隨時間消除，但仍有病患會抗拒所有的治療

帶狀泡疹神經痛

一般止痛劑抗病毒藥

嗎啡類止痛劑神經疼痛控制

局部藥物

類固醇

復健

疼痛的處置

• The WHO analgesic ladder

Strong -

opioid

+/- Non - opioid

+/- Adjuvant

Weak- opioid

+/- Non - opioid

Non – opioid

Anticonvulsants

Steroid

NSAID Aspirin

Acetaminophen

改善皰疹疼痛、肌肉麻痺雞尾酒療法

非藥物治療

使用冷熱療、電刺激、超音波

藥物治療口服外用注射

改善循環消炎止痛劑

Barbara P. Yawn, MD, MSc; Peter C. Wollan, PhD; Marge J. Kurland, RN; Jennifer L. St. Sauver, PhD; and Patricia Saddier, MD, PhD. Herpes Zoster Recurrences More Frequent Than Previously Reported. Mayo Clin Proc. • February 2011;86(2):88-93

Shingles Prevention Study (SPS) • Objectives

– Primary Objective

• To determine whether vaccination with a live attenuated varicella-zoster virus vaccine would decrease the incidence, severity, or both of herpes zoster and postherpetic neuralgia (PHN, pain≧3/10, ≧90 days after the onset of rash)

– Secondary Objectives

• To evaluate adverse events in a subpopulation of subjects

• To evaluate cell-mediated immunity in a subpopulation of subjects

• Design

– Randomized, multicenter (22 sites in US), double-blind, placebo-controlled study

• Randomization was stratified by age: 60–69 years, ≥70 years.

– 38,546 varicella history-positive, herpes zoster-negative adults 60 years of age or older

– Sub-studies: Immunologic (1,395); Adverse Events (AEMS) (6,616)

• Oxman MN et al. N Engl J Med. 2005;352:2271–2284.

Study Design

• Oxman MN et al. N Engl J Med. 2005;352:2271–2284.

SPS: Baseline Study Subjects Characteristics (1)

•Oxman MN et al. N Engl J Med. 2005;352:2271–2284.

SPS: Baseline Study Subjects Characteristics (2)


SPS: Overall Efficacy of ZOSTAVAX on Zoster Incidence

Compared With Placebo

•642

•315

•Placebo

•(n=19,247)

•ZOSTAVAX

•(n=19,254)

•Nu

mb

er

of

Zo

ste

r C

as

es

•51% •(95% CI: 44–58)

•OVERALL LOWER INCIDENCE OF ZOSTER

Overall, ZOSTAVAX significantly reduced the risk of herpes zoster in

subjects 60 years of age and older.

•Oxman MN et al. N Engl J Med. 2005;352:2271–2284. CI = confidence interval; SPS = Shingles Prevention Study.

SPS: Efficacy of ZOSTAVAX on Zoster Incidence

Compared With Placebo by Age Group (Years)

•334

•122

•Placebo

•(n=10,356)

•Nu

mb

er

of

Zo

ste

r C

as

es

•64%

•in subjects 60–69 yrs •(95% CI: 56–71)

•261

•156

•Placebo

•(n=7,559)

•ZOSTAVAX

•(n=7,621)

•Nu

mb

er

of

Zo

ste

r C

as

es

•41%

•in subjects 70–79 yrs •(95% CI: 28–52)

•47 •37

•Placebo

•(n=1,332)

•ZOSTAVAX

•(n=1,263)

•Nu

mb

er

of

Zo

ste

r C

as

es

•18%

•in subjects 80 yrs •(95% CI: –29–48; NS)

•ZOSTAVAX

•(n=10,370)

•Harpaz R et al. MMWR Recomm Rep. 2008;57(RR-5):1–30 CI = confidence interval; SPS = Shingles Prevention Study.

Vaccine efficacy for the prevention of herpes zoster was highest in those

subjects 60 to 69 years of age and declined with increasing age.

SPS: Postherpetic Neuralgia (PHN) in Patients 60 Years Who Developed Herpes Zoster

• PHN = Zoster-associated pain rated as ≥3 on a 10-point scale and occurring or persisting at least 90 days after rash onset.

•Harpaz R et al. MMWR Recomm Rep. 2008;57(RR-5):1–30 HZ = herpes zoster; PHN = postherpetic neuralgia;

• SPS = Shingles Prevention Study.

•aAge-adjusted estimate based on the age strata (60–69 and ≥70 years of age) at randomization.

•0

•Overall

•Number of PHN Cases •80 •27

•8.6

•12.5 •10

•20

•30

•% o

f Z

os

ter

Ca

se

s

Wit

h P

HN

• 39%a

(95% CI: 7–59)

•Placebo

•ZOSTAVAX®

•Number of HZ Cases •642 •315

•The benefit of ZOSTAVAX in the prevention of PHN can be primarily

attributed to the effect of the vaccine on the prevention of herpes zoster.

•SPS Safety Profile for ZOSTAVAX® in Patients 60 Years1

Vaccine-Related Injection-site and Systemic Reactions in ≥1% of Adults Who

Received ZOSTAVAX or Placebo (Days 0-42)

Adverse

Reaction

Solicited (%) Unsolicited (%)

Erythema Pain/

Tenderness Swelling Hematoma Pruritus Warmth

Headache

(Systemic)

ZOSTAVAX (n=3,345)

35.6 34.3 26.1 1.6 7.1 0.3 1.4

Placebo (n=3,271)

6.9 8.6 4.5 1.4 1.0 0.3 0.8

– The Adverse Event Monitoring Substudy (AEMS) (n=6,616)

– Vaccination report cards (VRCs)

– Most of these adverse events (AEs) were reported as mild in intensity

– Overall incidence of vaccine-related injection site AEs was significantly greater with ZOSTAVAX vs. placebo (48% vs. 17%), respectively


SPS: Immunogenicity Substudy

•Harpaz R et al. MMWR Morb Mortal Wkly Rep. 2008; 57(RR-5):1–30.

•gpELISA = glycoprotein enzyme-linked immunosorbent assay; SPS = Shingles Prevention Study.

•aAs measured by gpELISA.

ZOSTAVAX elicited higher varicella-zoster virus (VZV)–specific

antibody responses at 6 weeks after vaccination compared

with placebo.

•95% CI: 1.6–1.8

ZOSTAVAX Efficacy and Safety Trial (ZEST)

Baseline Characteristics

•N=Number of subjects randomized

n=Number of subjects contributing to each category

•SD = standard deviation; ZEST = ZOSTAVAX Efficacy and Safety Trial.

•aOther includes American Indian or Alaska Native, Multiracial, Native Hawaiian, or Other Pacific Islander.

•Schmader KE et al., Clin Infect Dis, 2012;54:922–928.

Characteristic ZOSTAVAX

(N=11,211)

Placebo

(N=11,228)

Sex, n (%)

Male

Female

4298 (38.3)

6913 (61.7)

4256 (37.9)

6972 (62.1)

Age, years

Mean ± SD

Range

54.9 ± 2.8

50 to 59

54.8 ± 2.8

50 to 59

Race, n (%)

White

Black

Asian

Othera

10,588 (94.4)

468 (4.2)

80 (0.7)

75 (0.7)

10,601 (94.4)

476 (4.2)

68 (0.6)

83 (0.7)

ZEST Primary Objective Results: Incidence of Confirmed

Herpes Zoster (HZ) Cases in ITT Population

ZOSTAVAX

(N=11,211)

Placebo

(N=11,228) Vaccine

Efficiency

With

Respect to

HZ

Point

Estimate

(95% CI)

n m

Total

Follow-Up Time

(Person-Years)

Estimated

Incidence

Rate of HZ

(Per 1000

Person-Years)

n m

Total

Follow-Up Time

(Person-Years)

Estimated

Incidence

Rate of HZ

(Per 1000

Person-

Years)

30 11,211 15,043 1.99 99 11,228 15,010 6.60 69.8%

(54.1–80.6)

p-value for testing the vaccine efficacy for HZ being less than 25% is <0.001.

N=Number of subjects randomized.

n=Number of confirmed HZ cases.

m=Number of subjects in the intent-to-treat (ITT) population.

•CI = confidence interval; ZEST = ZOSTAVAX Efficacy and Safety Trial.

• Schmader KE et al. Efficacy, Safety, and Tolerability of Herpes Zoster Vaccine in Persons Aged 50-59 Years, Clin Infect Dis, 2012;54:922–928.

•Efficacy of ZOSTAVAX on Incidence of HZ in Subjects 50 to 59 Years of Age

ZEST Exploratory Objective Results: Severity-by-Duration

Scores of Herpes Zoster (HZ) Pain in ITT Population


•Schmader KE et al. Efficacy, Clin Infect Dis, 2012;54:922–928.

ZOSTAVAX

(N=11,211)

Placebo

(N=11,228)

Relative

Reduction in

Mean HZ

Pain

Severity-by-

Duration

Score

[ZOSTAVAX

–Placebo]

Point

Estimate

(95% CI)

n m

Total

Follow-Up

Time

(Person-

Years)

Mean Severity-

by-Duration

Scores HZ Pain

n m

Total

Follow-Up

Time

(Person-

Years)

Mean Severity-

by-Duration

Scores HZ Pain

30 11,211 15,043 0.13 99 11,228 15,010 0.49 73.0%

(52.7–84.6)

N=Number of subjects randomized.

n=Number of confirmed HZ cases.

m=Number of subjects in the intent-to-treat (ITT) population.

ZEST Analysis of Varicella-Zoster Virus

gpELISA Antibody Responses

N=Number of subjects vaccinated in the Random Subcohort Population.

n=Number of subjects who had results either at prevaccination or 6 weeks postvaccination thus contributing to the

immunogenicity analysis.

•Week 6 Postvaccination

•Random Subcohort Population

•CI = confidence interval; gpELISA = glycoprotein enzyme-linked immunosorbent assay; GMT = geometric mean titer; ZEST = ZOSTAVAX Efficacy and Safety Trial.

•Schmader KE et al. 48th Annual Meeting of the Infectious Diseases Society of America. Poster 1380. October 21–24, 2010, Vancouver, Canada.

End Point

ZOSTAVAX

(N=1136)

Placebo

(N=1133) Estimated

GMT Ratio

(95% CI)

P Value

n Estimated

GMT n

Estimated

GMT

GMT 1124 663.7 1125 288.8 2.3 (2.2–2.4) <0.001

The specific antibody level that correlates with protection from zoster

has not been established.

ZEST Adverse Event Summary (Days 1 to 42 Postvaccination)

ZOSTAVAX Placebo Difference

(95% CI) n (%) n (%)

Subjects vaccinated in population with safety

follow-up

11,094 11,116

With one or more adverse events 8080 (72.8) 4613 (41.5) 31.3 (30.1–32.6)

Injection-site 7089 (63.9) 1596 (14.4) 49.5 (48.4–50.6)

Systemic 3932 (35.4) 3722 (33.5) 2.0 (0.7–3.2)

With vaccine-related adverse eventsa 7213 (65.0) 1988 (17.9) 47.1 (46.0–48.3)

Injection-site 7089 (63.9) 1596 (14.4) 49.5 (48.4–50.0)

Systemic 746 (6.7) 526 (4.7) 2.0 (1.4–2.6)

With serious adverse events 69 (0.6)c 61 (0.5)c 0.1 (–0.1–0.3)

Serious vaccine-related adverse eventsa 1 (0.0) 0 (0.0) 0.0 (0–0.1)

Who diedb 1 (0.0) 3 (0.0) 0.0 (0–0)


• Schmader KE et al. Clin Infect Dis, 2012;54:922–928.

•The same subject may appear in different categories but is counted only once in each category.

•aDetermined by the investigator to be possibly, probably, or definitely related to the vaccination. bAll deaths were determined not vaccine-related by the investigator. cRelative

risk of 1.13 (95% CI: 0.81–1.60).

Summary: ZOSTAVAX is Highly Effective in Reducing the Incidence

of Herpes Zoster and positive effects to Postherpetic Neuralgia

•% o

f Z

os

ter

ca

se

s w

ith

PH

N

•Nu

mb

er

of

HZ

•Placebo

•(n=642)* •ZOSTAVAX

•(n=315)*

•Nu

mb

er

of

HZ

Cases

•Placebo

•(n=11,228)

•ZOSTAVAX

•(n=11,211) •Placebo

•(n=19,247) •ZOSTAVAX

•(n=19,254)

•Overall % of Zoster cases with

Postherpetic Neuralgia (PHN)

In patients who develop HZ

postvaccination ≥60 y.o.

•Overall Incidence of

• Herpes Zoster (HZ)

•In patients ≥60 y.o.2

•Overall Incidence of

•Herpes Zoster (HZ)

• In patients 50-59 y.o.1

•51%

•Reduction •95%(CI: 44-58)

•39%


•70%


• ZOSTAVAX has demonstrated a favorable safety profile The incidence of serious adverse events (SAEs) was comparable to placebo

The most common adverse event is injection site reactions

ZOSTAVAX has demonstrated

a significantly higher varicella-zoster virus gpELISA antibody GMT at 6 weeks post-vaccination compared with placebo

•1. Schmader KE et al. Clin Infect Dis. 2012; 54: 922-928. 2. Oxman MN et al. N Engl J Med, 2005;352:2271–2284.

642

315

0

100

200

300

400

500

600

700

12.5

8.6

0

5

10

15

12.1

2.55

12

•* Number of Herpes zoster cases

•* ZOSTAVAX is not indicated for prevention of PHN

帶狀疱疹及其引起的併發症是可以預防的

• 施打帶狀疱疹疫苗是一項可用來降低患病的重要方式

疾病衛教預防

• 帶狀疱疹疾病的教育

• 罹患帶狀疱疹的風險意識，如年齡及併發症

• 了解預防及治療的途徑

1. National Library of Medicine. Posterherpetic Neuralgia. PubMed Health. NIH. June 28, 2011. 2. CDC Immunization. Immunization: Shingles Vaccine. www.cdc.gov/vaccines. Accessed 14 Feb 2013

帶狀疱疹疫苗的重要研究

兩項重要研究評估帶狀疱疹疫苗的功效、安全性、預防性及減輕疼痛的效果：

•帶狀疱疹預防研究(SPS)

– 38,546位60歲以上(19,270 ZOSTAVAX vs. 19,276 安慰劑)的男性及女性，無帶狀疱疹病史

– 子研究：免疫製劑(1,395); 藥物不良反應(AEMS) (6,616)

•效果及安全性測試(ZEST)

– 22,439位曾得過水痘但無帶狀疱疹病史的男性及女性

– 年齡介於50 至 59 歲之間(11,211 ZOSTAVAX vs. 11,228 安慰劑)

1. Merck & Co. World Product Circular ZOSTAVAX. WPC-V211-ZST-R-I-072011. 2011:1-24

帶狀疱疹預防研究(SPS)

•帶狀疱疹預防研究(SPS)

– 與施打安慰劑相比，ZOSTAVAX明顯地減少罹患帶狀疱疹風險達51%

– ZOSTAVAX 在預防帶狀疱疹的效果上，對60-69歲間的老年人是最顯著的—減少罹患風險達64%

– 與施打安慰劑相比，ZOSTAVAX降低帶狀疱疹後神經痛的整體發生率，達到67%，效果令人滿意

1. Merck & Co. World Product Circular ZOSTAVAX. WPC-V211-ZST-R-I-072011. 2011:1-24. 2. Oxman et al. N Engl J Med. 2005;352:2271-2284

12.5

8.6

0

5

10

15

20

25

30

80

642

% o

f H

Z C

as

es

Wit

h P

HN

27

315

67% (95% CI: 48–79) Number of PHN Cases

Number of HZ Cases

帶狀疱疹預防研究: 減少發生帶狀疱疹後神經痛的效果帶狀疱疹後神經痛 :假如將疼痛程度分為10個等級，帶狀疱疹引起的疼痛程度不

小於等級3，同時疼痛感自水泡紅疹出現後至少持續90天

Placebo

(n=19,247)

ZOSTAVAX

(n=19,254)

Oxman, M.N. A Vaccine to Prevent Herpes Zoster and Postherpetic Neuralgia in Older Adults.

N Engl J Med 2005 352:22, 2271-84.

• ZOSTAVAX 效果及安全性測試的結果顯示， ZOSTAVAX 能大幅降低50-59歲間男女性帶狀疱疹的發生率

• 與施打安慰劑相比，ZOSTAVAX有效降低帶狀疱疹發生率達70%(30個案例 vs. 99個案例)

• 普遍來說，病患對ZOSTAVAX的耐受度佳

效果及安全性測試(ZEST)

1. Merck & Co. World Product Circular ZOSTAVAX. WPC-V211-ZST-R-I-072011. 2011:1-24

A Phase III Clinical Trial to Study the Safety, Tolerability, and Immunogenicity of Zoster Vaccine Live (Oka/Merck) in Subjects With a Prior History of Herpes

Zoster

•Mills R et al. Vaccine 28 (2010) 4204-4209.

Statistical Analysis of VZV gpELISA Antibody Titer:

4 weeks post vaccination

Endpoint ZOSTAVAX

N = 100

Placebo

N = 50

Estimated GMT Ratio

(ZOSTAVAX vs. Placebo)

(95% CI)

p-Value#

n Estimated GMT

n Estimated GMT

GMT 100 811.5 50 392.7 2.07 (1.48, 2.88) <0.001

VZV = Varicella-zoster virus

CI = Confidence Interval

GMT = Geometric Mean Titer

•Mills R et al. Vaccine 28 (2010) 4204-4209

Clinical Adverse Experience Summary (Day 1 to 28)

Following Any Vaccination

ZOSTAVAX®

(N=100)

Placebo

(N=101)

n (%) n (%)

Subjects in population

Subjects with follow-up

Number (%) of subjects:

with no adverse experience

with one or more adverse experience

Injection-site adverse experience

Systemic adverse experience

with vaccine-related adverse experience

Injection-site adverse experience

Systemic adverse experience

With serious adverse experiences

100

98

47 (48.0)

51 (52.0)

45 (45.9)

15 (15.3)

45 (45.9)

45 (45.9)

2 (2.0)

0 (0.0)

101

96

79 (82.3)

17 (17.7)

4 (4.2)

13 (13.5)

4 (4.2)

4 (4.2)

0 (0.0)

0 (0.0)

Post Marketing studies in USA

•Reference: Shingles (Herpes Zoster) Vaccine (Zostavax): A Review of Its Use in the Prevention of Herpes

Zoster and Postherpetic Neuralgia in Adults Aged >50 Years. Gillian M. Keating. Drugs (2013) 73:1227–1244

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