Herpes zoster (HZ) or “shingles” occurs when the varicella zoster virus (VZV), lying latent in the sensory ganglia, becomes reactivated. An HZ outbreak typically presents as a vesicular skin eruption most characteristically forming a painful girdle around one side of the thorax. The rash and pain usually resolve over a few weeks. However, about 10% of patients with shingles develop some degree of persistent HZ-related pain (post-herpetic neuralgia or PHN).1
Health Canada approved a two-dose adjuvanted herpes zoster subunit vaccine (Shingrix) in October 2017.
Zostavax, a live attenuated vaccine, was approved 10 years ago. Both vaccines are for the prevention of HZ in people ≥ 50, but neither is approved for prevention of PHN.
More than 90% of Canadian adults have had chicken pox (VZV) infection.2 A major risk factor for developing HZ is increased age, with an incidence of 6 to 8 per thousand people per year at age 60, and 8 to 12 per thousand people per year at age 80.3 About 5% of people with HZ experience recurrence.4 Population-based data in British Columbia reports that the overall HZ incidence increased from 3.2 per thousand in 1997 to 4.5 per thousand in 2012, but the increase in incidence may reflect an increase in reporting.4
We used Cochrane systematic review methods for the literature search, data collection and analysis, and risk of bias assessment. We included randomized controlled trials (RCTs) of Shingrix versus active vaccine, no vaccine or placebo. We sought out and included related unpublished data from registries5,6 and clinical study reports7,8.
Five RCTs (with about 32,000 participants) met our inclusion criteria.9-13 No trials directly compared Shingrix to Zostavax. Three trials included a placebo comparator and were meta-analyzed.9-11 In our pooled analysis, HZ occurred in 0.28% of patients who received the HZ vaccine versus 3.54% for placebo over about 3.5 years. This translates to a Number Needed to Vaccinate (NNV) of about 31 to prevent 1 case of HZ over 3.5 years. The incidence of post-herpetic neuralgia (PHN) declined in RCTs in proportion to the reduction of HZ, but the absolute reduction is much smaller, NNV = 358.9,10 Not all PHN is severe or lasts for years. Of every 10 patients vaccinated, 8 or 9 had an adverse effect, most commonly injection-site pain, myalgia or fatigue lasting up to a few days. There was no difference in serious adverse events in around 4 years of follow-up, or withdrawals due to adverse events.
Two additional studies did not report on clinical efficacy outcomes of interest and reported insufficient information on safety.12,13
Our full systematic review is available on our website.1
Risk of bias of included studies
All included studies were funded by the manufacturer. Other limitations include the use of data carried from last point of patient contact for patient withdrawals, selective reporting of some patient analyses and substantial inconsistency in the magnitude of vaccine effect when pooling study data. Overall, we graded the certainty of evidence as moderate.1
- Compared to placebo the Shingrix vaccine reduced the incidence of herpes zoster by 3.26 % (NNV = 31) over 3.5 years in all age groups and reduced the incidence of post-herpetic neuralgia by 0.28% (NNV ≈ 350).
- Compared to placebo Shingrix increased grade 3 systemic reactions (which prevented normal daily activities for about 1-3 days) by 4 to 9% (NNH 11 to 25).
- The effectiveness (i.e. maintained protection) and safety of Shingrix are still unknown beyond about four years.
- Discuss the balance of baseline herpes zoster risk, harms, benefits and costs when considering this vaccine.
Shingrix clinical evidence
|Indication||Prevention of herpes zoster (HZ) or “shingles” in people age 50 or older|
|Findings from main
|Duration of HZ protection||Unknown beyond 4 years|
|Cost||Approximately $300 per two-shot series in BC|
The draft of this Therapeutics Letter was submitted for review to 130 experts and primary care physicians in order to correct any inaccuracies and to ensure that the information is concise and relevant to clinicians.
- Therapeutics Initiative. Systematic review report: Efficacy and safety of adjuvanted herpes zoster subunit vaccine. October 2018. https://ti.ubc.ca/shingrix
- Canadian Immunization Guide, Public Health Agency of Canada. Herpes zoster (shingles) vaccine. 2014. https://www.canada.ca/en/public-health/services/publications/healthy-living/canadian-immunization-guide-part-4-active-vaccines/page-8-herpes-zoster-(shingles)-vaccine.html
- Kawai K, Gebremeskel BG, Acosta CJ. Systematic review of incidence and complications of herpes zoster: towards a global perspective. BMJ Open 2014;4:e004833. DOI: 10.1136/bmjopen-2014-004833
- Marra F, Chong M, Najafzadeh M. Increasing incidence associated with herpes zoster infection in British Columbia, Canada. BMC Infectious Diseases. 2016;16(1):589. DOI: 10.1186/s12879-016-1898-z
- ClinicalTrials.gov. Immunogenicity and safety of GlaxoSmithKline (GSK) Biologicals’ herpes zoster subunit (HZ/su) vaccine in adults 18 years of age or older with renal transplant. (updated Aug 2018) https://clinicaltrials.gov/ct2/show/NCT02058589
- ClinicalTrials.gov. Study to evaluate efficacy, safety, and immunogenicity of GlaxoSmithKline (GSK) Biologicals’ herpes zoster vaccine GSK1437173A. (updated Jan 2018) https://clinicaltrials.gov/ct2/show/NCT01610414
- GlaxoSmithKline Biologicals, SA. Clinical Study Report for Study 113077 (ZOSTER-022). GSK Clinical Study Register. https://www.gsk-clinicalstudyregister.com/files2/gsk-113077-clinical-study-report-redact.pdf
- GlaxoSmithKline Biologicals, SA. Clinical Study Report for Study 110390 (ZOSTER-006). GSK Clinical Study Register. https://www.gsk-clinicalstudyregister.com/files2/gsk-110390-clinical-study-report-redact.pdf
- Cunningham AL, Lal H, Kovac M, et al. Efficacy of the herpes zoster subunit vaccine in adults 70 years of age or older. N Engl J Med. 2016;375(11):1019-32. DOI: 10.1056/NEJMoa1603800
- Lal H, Cunningham AL, Godeaux O, et al. Efficacy of an adjuvanted herpes zoster subunit vaccine in older adults. N Engl J Med. 2015;372(22):2087-96. DOI: 10.1056/NEJMoa1501184
- Chlibek R, Bayas JM, Collins H, et al. Safety and immunogenicity of an ASO1-adjuvanted varicella-zoster virus subunit candidate vaccine against herpes zoster in adults ≥50 years of age. J Infect Dis. 2013;208(12):953-61. DOI: 10.1093/infdis/jit365
- Leroux-Roels I, Leroux-Roels G, Clement F, et al. A phase 1/2 clinical trial evaluating safety and immunogenicity of a varicella zoster glycoprotein E subunit vaccine candidate in young and older adults. J Infect Dis. 2012;206(8):1280-90. DOI: 10.1093/infdis/jis497
- Chlibek R, Smetana J, Pauksens K, et al. Safety and immunogenicity of three different formulations of an adjuvanted varicella-zoster virus subunit candidate vaccine in older adults: A phase II, randomized controlled study. Vaccine. 2014;32(15):1745-53. DOI: 10.1016/j.vaccine.2014.01.019
- Berkowitz EM, Moyle G, Stellbrink HJ, et al. Safety and immunogenicity of an adjuvanted herpes zoster subunit candidate vaccine in HIV-infected adults: A phase 1/2a randomized, placebo-controlled study. J Infect Dis 2015;211(8):1279-87. DOI: 10.1093/infdis/jiu606
- Stadtmauer EA, Sullivan KM, Marty FM, et al. A phase 1/2 study of an adjuvanted varicella-zoster virus subunit vaccine in autologous hematopoietic cell transplant recipients. Blood. 2014;124(19):2921-9. DOI: 10.1182/blood-2014-04-573048
- Godeaux O, Kovac M, Shu D, et al. Immunogenicity and safety of an adjuvanted herpes zoster subunit candidate vaccine in adults ≥ 50 years of age with a prior history of herpes zoster: A phase III, non-randomized, open-label clinical trial. Hum Vaccin Immunother. 2017;13(5):1051-58. DOI: 10.1080/21645515.2016.1265715
- Grupping K, Campora L, Douha M, et al. Immunogenicity and safety of the HZ/su adjuvanted herpes zoster subunit vaccine in adults previously vaccinated with a live attenuated herpes zoster vaccine. J Infect Dis. 2017;216(11):1343-51. DOI: 10.1093/infdis/jix482