Skip to main content

Main menu

  • Home
  • Content
    • First Release
    • Current
    • Archives
    • Collections
    • Audiovisual Rheum
    • COVID-19 and Rheumatology
  • Resources
    • Guide for Authors
    • Submit Manuscript
    • Payment
    • Reviewers
    • Advertisers
    • Classified Ads
    • Reprints and Translations
    • Permissions
    • Meetings
    • FAQ
    • Policies
  • Subscribers
    • Subscription Information
    • Purchase Subscription
    • Your Account
    • Terms and Conditions
  • About Us
    • About Us
    • Editorial Board
    • Letter from the Editor
    • Duncan A. Gordon Award
    • Privacy/GDPR Policy
    • Accessibility
  • Contact Us
  • JRheum Supplements
  • Services

User menu

  • My Cart
  • Log In
  • Log Out

Search

  • Advanced search
The Journal of Rheumatology
  • JRheum Supplements
  • Services
  • My Cart
  • Log In
  • Log Out
The Journal of Rheumatology

Advanced Search

  • Home
  • Content
    • First Release
    • Current
    • Archives
    • Collections
    • Audiovisual Rheum
    • COVID-19 and Rheumatology
  • Resources
    • Guide for Authors
    • Submit Manuscript
    • Payment
    • Reviewers
    • Advertisers
    • Classified Ads
    • Reprints and Translations
    • Permissions
    • Meetings
    • FAQ
    • Policies
  • Subscribers
    • Subscription Information
    • Purchase Subscription
    • Your Account
    • Terms and Conditions
  • About Us
    • About Us
    • Editorial Board
    • Letter from the Editor
    • Duncan A. Gordon Award
    • Privacy/GDPR Policy
    • Accessibility
  • Contact Us
  • Follow jrheum on Twitter
  • Visit jrheum on Facebook
  • Follow jrheum on LinkedIn
  • Follow jrheum on YouTube
  • Follow jrheum on Instagram
  • Follow jrheum on RSS
Research ArticleOther Arthritides

Longterm Effectiveness of Herpes Zoster Vaccine among Patients with Autoimmune and Inflammatory Diseases

Huifeng Yun, Fenglong Xie, John W. Baddley, Kevin Winthrop, Kenneth G. Saag and Jeffrey R. Curtis
The Journal of Rheumatology July 2017, 44 (7) 1083-1087; DOI: https://doi.org/10.3899/jrheum.160685
Huifeng Yun
From the University of Alabama at Birmingham, Birmingham, Alabama; Oregon Health and Science University, Portland, Oregon, USA.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Fenglong Xie
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
John W. Baddley
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Kevin Winthrop
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Kenneth G. Saag
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Jeffrey R. Curtis
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: jcurtis@uab.edu
  • Article
  • Figures & Data
  • Info & Metrics
  • References
  • PDF
  • eLetters
PreviousNext
Loading

Abstract

Objective. The protection duration of herpes zoster (HZ) vaccination is unclear among patients with autoimmune (AI) diseases.

Methods. Using 2006–2013 Medicare data, HZ vaccinated patients with AI were matched 1:2 to unvaccinated HZ. Incidence rates (IR) and adjusted risk ratios over time were calculated using Poisson regression.

Results. Of 59,627 vaccinated patients, crude IR increased from 0.75/100 person-years during the first year post-vaccination to 1.25 during the seventh year. Vaccinated patients had a significantly lower risk of HZ compared with the unvaccinated through 5 years.

Conclusion. HZ vaccination was significantly protective only for about 5 years among patients with AI.

Key Indexing Term:
  • AUTOIMMUNE DISEASES
  • INFECTION
  • VACCINATION
  • HERPES ZOSTER

The pain caused by herpes zoster (HZ), also known as shingles, is sometimes severe and may have a major effect on quality of life1,2. Although antiviral treatment of HZ can reduce the severity and duration of HZ, it may not prevent postherpetic neuralgia3. To prevent HZ and postherpetic neuralgia, the US Centers for Disease Control recommended the live HZ vaccine for healthy adults aged 60 years and older4.

The Shingles Prevention Study (SPS) showed that HZ vaccine reduced the incidence of HZ by 51% and remained efficacious for several years among immunocompetent patients5,6. In longterm followup of SPS participants, HZ vaccination was shown to lose most of its protective benefit over 10 years7. Although observational studies have reported that HZ vaccine significantly reduces HZ and postherpetic neuralgia in patients with autoimmune or inflammatory (AI) conditions8,9, the duration of protection among patients with AI, who might have an attenuated vaccine response because of immune suppression, is unclear. Therefore, we evaluated the duration of HZ vaccine effectiveness among older patients with AI.

MATERIALS AND METHODS

Data sources and study design

Using 2006–2013 Medicare data, we conducted a retrospective cohort study among 100% of patients with AI diseases, including rheumatoid arthritis (RA), ankylosing spondylitis (AS), inflammatory bowel disease (IBD), psoriasis, and psoriatic arthritis (PsA). Medicare is the US health insurance program for people age 65 or older and for younger people with disabling conditions (e.g., RA). Medicare data include information on diagnoses, procedures, hospitalizations, physician visits, and prescriptions. Both Medicare and the Institutional Review Board of the University of Alabama at Birmingham approved the study: X121029003.

Study population and eligible criteria

After patients with RA (714.x), AS (720.0x), IBD (555.x, 556.x), psoriasis (696.1x), or PsA (696.0x) were identified using ≥ 2 physician International Classification of Diseases, 9th ed (ICD-9) diagnosis codes10, we identified patients who had HZ vaccinations using current procedural terminology (CPT) code 90736 or National Drug Codes (NDC). The vaccination date was determined as the CPT code date or the NDC date if no corresponding CPT was found within 7 days after the NDC date.

Eligible patients were required to have ≥ 12 months continuous Medicare fee-for-service coverage (baseline) before vaccination and throughout followup. We excluded patients with ICD-9 diagnosis codes or prescriptions for HZ during baseline. Vaccinated patients were matched 1:2 to unvaccinated on calendar year, age, sex, race, AI disease, and use of biologics, disease-modifying antirheumatic drugs (DMARD), and glucocorticoids. Biologic and DMARD were categorized as dichotomous, whereas the average glucocorticoid prednisone–equivalent dose during the 6 months before vaccination was categorized as none, < 7.5 mg/day, and ≥ 7.5 mg/day. To understand longterm effectiveness and avoid misclassification related to healthcare associated with vaccine administration, followup started from 30 days after the vaccination date or corresponding calendar date in the matched cohort, and ended at the earliest of first HZ, death, loss of coverage, or December 31, 2013. Matched patients were censored if they were subsequently vaccinated, and then included in the vaccination group and re-matched. The maximum followup time was 7 years post-vaccination.

Outcome

The outcome was first HZ event during followup. We identified HZ using an ICD-9 inpatient diagnosis code alone (053.x) or an outpatient diagnosis code plus antiviral medication (famciclovir, acyclovir, valacyclovir) within 7 days of HZ diagnosis. This previously validated algorithm has high positive predictive value (PPV ≥ 85%)11,12.

Potential confounders

Besides matching factors, we evaluated other potential confounders including baseline medical conditions and concurrent medications, and updated them in each followup year. Medical conditions include diabetes, chronic obstructive pulmonary disease, renal disease, heart failure, and outpatient infections. Concurrent medications included narcotics, antidepressant drugs, and nonsteroidal antiinflammatory drugs.

Statistical analysis

We conducted descriptive analysis for potential confounders by HZ vaccination status. We calculated incidence rates (IR) for each year of post-vaccination stratified by whether patients were vaccinated. Using matched, unvaccinated patients as referent13,14, conditional Poisson regression for repeated measures was applied to calculate the adjusted risk ratio (RR) of HZ each year of post-vaccination, controlling for matched variables and additional potential confounders. Analyses were conducted using SAS 9.3 (SAS Institute).

Sensitivity and subgroup analyses

We conducted a sensitivity analysis that identified HZ only using inpatient or outpatient diagnosis codes (053.x) without requiring antiviral drug use. We conducted subgroup analyses to evaluate HZ vaccine effectiveness stratified by age (< 70 and ≥ 70 years) and glucocorticoid dose category.

RESULTS

The vaccinated cohort consisted of 59,627 patients, whereas the matched unvaccinated cohort included 119,254 patients. The factors on which patients were matched were balanced as expected (Table 1). Mean age in both groups was 73.5 years, and 53.1% of the cohort had RA, 31.6% psoriasis, 4.7% PsA, 20.9% IBD, and 1.4% AS.

View this table:
  • View inline
  • View popup
Table 1.

Baseline characteristics for the vaccinated cohort and matched unvaccinated cohort. Values are % unless otherwise specified.

As shown in Figure 1, HZ IR in the vaccinated group increased from 0.75 per 100 person-years (PY) in the first-year post-vaccination to 1.25 in the seventh year post-vaccination. In contrast, the HZ IR among the unvaccinated remained relatively constant (1.3 to 1.7/100 PY) through 7 years of followup. After adjusting for matched variable and potential confounders (all in Table 1), vaccinated patients had significantly lower risk of HZ compared with unvaccinated patients over 5 years. The relative risk for HZ during years 3–5 ranged from 0.74–0.77, and the upper bound of the 95% CI ranged from 0.87–0.97. This protective effect was not significant during the sixth and seventh years after vaccination (Figure 2).

Figure 1.
  • Download figure
  • Open in new tab
  • Download powerpoint
Figure 1.

IR and 95% CI for herpes zoster over time among vaccinated patients compared with the matched unvaccinated patients. IR: incidence rate.

Figure 2.
  • Download figure
  • Open in new tab
  • Download powerpoint
Figure 2.

Adjusted RR of herpes zoster by years of post-vaccination compared with the matched unvaccinated patients. RR: risk ratio.

Both sensitivity analyses that did not require HZ treatment yielded similar results as our main analysis and subgroup analyses that stratified by patient’s age and glucocorticoid dosage categories yielded consistent trends with the main analysis (not shown).

DISCUSSION

There has been some concern that patients with AI conditions might have a lower immunogenic response to HZ vaccination, especially when treated with immunosuppressive medications such as glucocorticoids15,16. Reassuringly, we found that in older patients with autoimmune diseases, the HZ vaccine was effective in the short term, and that its effectiveness waned over time. HZ risk was most reduced in the first-year post-vaccination and increased back to the unvaccinated rate over about 5–7 years.

The attenuating effectiveness over time of HZ vaccination observed in our analysis has been reported in the general population, although in healthy older people, the protection associated with vaccination appears to last somewhat longer. A previous analysis reported that the vaccine efficacy declined after the first year post-vaccination, but remained significantly protective for at least 5 years6. Likewise, the subsequently published Long Term Persistence Substudy showed that vaccine effectiveness continued to decline, but remained statistically significant through Year 8 post-vaccination7. In addition, an observational study conducted among healthy older members of the Kaiser Permanente Northern California in 2007–2013 also found that HZ vaccine effectiveness in routine use waned over time. In that observational analysis, the protective effects of vaccination remained significant over 7 years following vaccination17. Our study found that HZ vaccination was significantly protective in the short term. The nonsignificant effectiveness during years 6–7 post-vaccination may result from small numbers, but the effect estimates of the vaccine’s benefit by Year 7 were negligible (IRR 0.96), irrespective of the 95% CI.

As expected, our study conducted in patients with AI diseases had higher absolute incidence rates of HZ in each post-vaccination year than those reported in the general population. In unvaccinated healthy older people in the SPS, the absolute IR was 1.1 per 100 PY in patients aged 70 and older. Rates in our study were about 50% increased, consistent with prior observations that have found elevated rates of HZ in patients with AI18.

Unlike randomized trials, our observational study lacked detailed information on disease activity and clinical factors, and thus residual confounding is possible. Although the claims-based algorithm for HZ has been shown to have good PPV, medical records were not available to confirm HZ, so misclassification was possible, although unlikely to be differential by vaccination status. Additionally, misclassification of HZ vaccination was possible if individuals paid for their vaccination without using insurance coverage. However, because all patients were required to have full coverage and given the expense of the vaccine (> $200), vaccination administration not identified by Medicare should have been rare. Finally, the insignificant effectiveness during years 6–7 may be due to the limited events and person-time; however, the clinical benefits in these 2 years are limited, and the reported RR estimates were close to 1.

The duration of HZ vaccine effectiveness waned over about 5 years among older patients with AI conditions, many of whom were treated with immunosuppressive and immunomodulatory agents. This finding raises the possibility that patients might benefit from a booster vaccine at some point after initial vaccination, although no recommendation currently exists that would support such a practice. Further research is needed to determine when and if such a strategy is effective.

Footnotes

  • H. Yun received research support from Amgen. Dr. Baddley received research support from BMS. Dr. Winthrop received research support from Pfizer. Dr. Saag received research support from Amgen, and consulting fees from Amgen and Astra Zeneca. Dr. Curtis received research support from Amgen, Pfizer, Crescendo, Corrona, and consulting fees from Amgen, Janssen, Pfizer, and Corrona.

  • Accepted for publication January 31, 2017.

REFERENCES

  1. 1.↵
    1. Cohen JI
    . Herpes zoster. N Engl J Med 2013;369:1766–7.
    OpenUrlCrossRef
  2. 2.↵
    1. Langan SM,
    2. Smeeth L,
    3. Margolis DJ,
    4. Thomas SL
    . Herpes zoster vaccine effectiveness against incident herpes zoster and post-herpetic neuralgia in an older US population: a cohort study. PLoS Med 2013;10:e1001420.
    OpenUrlCrossRefPubMed
  3. 3.↵
    1. Dworkin RH,
    2. Schmader KE
    . Treatment and prevention of postherpetic neuralgia. Clin Infect Dis 2003;36:877–82.
    OpenUrlAbstract/FREE Full Text
  4. 4.↵
    1. Centers for Disease Control and Prevention
    . Prevention of herpes zoster. Recommendations of the Advisory Committee on Immunization Practices (ACIP). [Internet. Accessed February 8, 2017.] Available from: www.cdc.gov/Mmwr/preview/mmwrhtml/rr57e0515a1.htm
  5. 5.↵
    1. Oxman MN,
    2. Levin MJ,
    3. Johnson GR,
    4. Schmader KE,
    5. Straus SE,
    6. Gelb LD,
    7. et al.
    A vaccine to prevent herpes zoster and postherpetic neuralgia in older adults. N Engl J Med 2005;352:2271–84.
    OpenUrlCrossRefPubMed
  6. 6.↵
    1. Schmader KE,
    2. Oxman MN,
    3. Levin MJ,
    4. Johnson G,
    5. Zhang JH,
    6. Betts R,
    7. et al;
    8. Shingles Prevention Study Group
    . Persistence of the efficacy of zoster vaccine in the shingles prevention study and the short-term persistence substudy. Clin Infect Dis 2012;55:1320–8.
    OpenUrlAbstract/FREE Full Text
  7. 7.↵
    1. Morrison VA,
    2. Johnson GR,
    3. Schmader KE,
    4. Levin MJ,
    5. Zhang JH,
    6. Looney DJ,
    7. et al;
    8. Shingles Prevention Study Group
    . Long-term persistence of zoster vaccine efficacy. Clin Infect Dis 2015;60:900–9.
    OpenUrlAbstract/FREE Full Text
  8. 8.↵
    1. Zhang J,
    2. Xie F,
    3. Delzell E,
    4. Chen L,
    5. Winthrop KL,
    6. Lewis JD,
    7. et al.
    Association between vaccination for herpes zoster and risk of herpes zoster infection among older patients with selected immune-mediated diseases. JAMA 2012;308:43–9.
    OpenUrlPubMed
  9. 9.↵
    1. Zhang J,
    2. Delzell E,
    3. Curtis JR
    . Postherpetic neuralgia after herpes zoster vaccination—reply. JAMA 2012;308:1427–8.
    OpenUrlPubMed
  10. 10.↵
    1. Herrinton LJ,
    2. Curtis JR,
    3. Chen L,
    4. Liu L,
    5. Delzell E,
    6. Lewis JD,
    7. et al.
    Study design for a comprehensive assessment of biologic safety using multiple healthcare data systems. Pharmacoepidemiol Drug Saf 2011;20:1199–209.
    OpenUrlCrossRefPubMed
  11. 11.↵
    1. Donahue JG,
    2. Choo PW,
    3. Manson JE,
    4. Platt R
    . The incidence of herpes zoster. Arch Intern Med 1995;155:1605–9.
    OpenUrlCrossRefPubMed
  12. 12.↵
    1. Mullooly JP,
    2. Riedlinger K,
    3. Chun C,
    4. Weinmann S,
    5. Houston H
    . Incidence of herpes zoster, 1997–2002. Epidemiol Infect 2005;133:245–53.
    OpenUrlCrossRefPubMed
  13. 13.↵
    1. Farrington CP
    . Relative incidence estimation from case series for vaccine safety evaluation. Biometrics 1995;51:228–35.
    OpenUrlCrossRefPubMed
  14. 14.↵
    1. Cameron AC,
    2. Trivedi PK
    . Regression analysis of count data. New York: Cambridge University Press; 1998.
  15. 15.↵
    1. Adler S,
    2. Krivine A,
    3. Weix J,
    4. Rozenberg F,
    5. Launay O,
    6. Huesler J,
    7. et al.
    Protective effect of A/H1N1 vaccination in immune-mediated disease—a prospectively controlled vaccination study. Rheumatology 2012;51:695–700.
    OpenUrlAbstract/FREE Full Text
  16. 16.↵
    1. Bingham CO 3rd,
    2. Looney RJ,
    3. Deodhar A,
    4. Halsey N,
    5. Greenwald M,
    6. Codding C,
    7. et al.
    Immunization responses in rheumatoid arthritis patients treated with rituximab: results from a controlled clinical trial. Arthritis Rheum 2010;62:64–74.
    OpenUrlCrossRefPubMed
  17. 17.↵
    1. Tseng HF,
    2. Harpaz R,
    3. Luo Y,
    4. Hales CM,
    5. Sy LS,
    6. Tartof SY,
    7. et al.
    Declining effectiveness of herpes zoster vaccine in adults aged ≥60 years. J Infect Dis 2016;213:1872–5.
    OpenUrlAbstract/FREE Full Text
  18. 18.↵
    1. Yun H,
    2. Yang S,
    3. Chen L,
    4. Xie F,
    5. Winthrop K,
    6. Baddley JW,
    7. et al.
    Risk of herpes zoster in autoimmune and inflammatory diseases: implications for vaccination. Arthritis Rheumatol 2016;68:2328–37.
    OpenUrl
PreviousNext
Back to top

In this issue

The Journal of Rheumatology
Vol. 44, Issue 7
1 Jul 2017
  • Table of Contents
  • Table of Contents (PDF)
  • Index by Author
  • Editorial Board (PDF)
Print
Download PDF
Article Alerts
Sign In to Email Alerts with your Email Address
Email Article

Thank you for your interest in spreading the word about The Journal of Rheumatology.

NOTE: We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. We do not capture any email address.

Enter multiple addresses on separate lines or separate them with commas.
Longterm Effectiveness of Herpes Zoster Vaccine among Patients with Autoimmune and Inflammatory Diseases
(Your Name) has forwarded a page to you from The Journal of Rheumatology
(Your Name) thought you would like to see this page from the The Journal of Rheumatology web site.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Citation Tools
Longterm Effectiveness of Herpes Zoster Vaccine among Patients with Autoimmune and Inflammatory Diseases
Huifeng Yun, Fenglong Xie, John W. Baddley, Kevin Winthrop, Kenneth G. Saag, Jeffrey R. Curtis
The Journal of Rheumatology Jul 2017, 44 (7) 1083-1087; DOI: 10.3899/jrheum.160685

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero

 Request Permissions

Share
Longterm Effectiveness of Herpes Zoster Vaccine among Patients with Autoimmune and Inflammatory Diseases
Huifeng Yun, Fenglong Xie, John W. Baddley, Kevin Winthrop, Kenneth G. Saag, Jeffrey R. Curtis
The Journal of Rheumatology Jul 2017, 44 (7) 1083-1087; DOI: 10.3899/jrheum.160685
del.icio.us logo Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Google Plus One
Bookmark this article

Jump to section

  • Article
    • Abstract
    • MATERIALS AND METHODS
    • RESULTS
    • DISCUSSION
    • Footnotes
    • REFERENCES
  • Figures & Data
  • Info & Metrics
  • References
  • PDF
  • eLetters

Keywords

AUTOIMMUNE DISEASES
INFECTION
VACCINATION
HERPES ZOSTER

Related Articles

Cited By...

More in this TOC Section

  • Immunoglobulin A Vasculitis Following COVID-19: A French Multicenter Case Series
  • How Is Health Equity Assessed in Cochrane Musculoskeletal Reviews?
  • Immune Response to SARS-CoV-2 Third Vaccine in Patients With Rheumatoid Arthritis Who Had No Seroconversion After Primary 2-Dose Regimen With Inactivated or Vector-Based Vaccines
Show more Other Arthritides

Similar Articles

Keywords

  • autoimmune diseases
  • infection
  • vaccination
  • HERPES ZOSTER

Content

  • First Release
  • Current
  • Archives
  • Collections
  • Audiovisual Rheum
  • COVID-19 and Rheumatology

Resources

  • Guide for Authors
  • Submit Manuscript
  • Author Payment
  • Reviewers
  • Advertisers
  • Classified Ads
  • Reprints and Translations
  • Permissions
  • Meetings
  • FAQ
  • Policies

Subscribers

  • Subscription Information
  • Purchase Subscription
  • Your Account
  • Terms and Conditions

More

  • About Us
  • Contact Us
  • My Alerts
  • My Folders
  • Privacy/GDPR Policy
  • RSS Feeds
The Journal of Rheumatology
The content of this site is intended for health care professionals.
Copyright © 2022 by The Journal of Rheumatology Publishing Co. Ltd.
Print ISSN: 0315-162X; Online ISSN: 1499-2752
Powered by HighWire