Herpes Zoster Vaccine and IBD Research at Penn

Image of herpes zoster virus at the molecular level.

Clinician researchers at Penn GI have been investigating herpes zoster (shingles) in patients with inflammatory bowel disease (IBD) exposed to antisuppressants, and the safety of herpes zoster vaccination (HZV) among IBD patients on anti-TNF therapy.


Herpes zoster (HZ), also known as shingles, results from reactivation of latent varicella zoster in the cranial nerves or dorsal root ganglia, and presents as painful unilateral vesicular eruption along a dermatomal distribution, with a lifetime incidence rising to 50% in persons surviving to 85 years. [1] Although HZ resolves by itself in a majority of cases, it can have a complicated course, resulting in neurological and ocular complications as well as post herpetic neuralgia (PHN) which can be debilitating. [2, 3] Patients with inflammatory bowel disease (IBD) are at an increased risk of developing HZ but research in this field is lacking.

To address this concern, Dr. Nabeel Khan† and colleagues from the IBD Center at Penn Gastroenterology conducted three retrospective cohort studies involving more than 56,000 IBD patients over a 16-year period in the US National Veterans Affairs healthcare system (VAHS). The findings of these studies were published in Alimentary Pharmacology & Therapeutics, Inflammatory Bowel Disease and Clinical Gastroenterology and Hepatology. [4, 5, 6]

†Director of GI at the Corporal Michael J. Crescenz VA Medical Center in Philadelphia.


The first study [4] found that IBD by itself was associated with an increased risk of HZ, with the adjusted HRs being 1.81 for ulcerative colitis (UC), 1.56 for Crohn’s disease (CD), and 1.72 for IBD. In multivariable Cox regression analysis, compared to exposure to 5-ASA alone, exposure to thiopurines or a combination of thiopurines and anti-TNF agents was associated with increased risk of HZ. However, exposure to anti-TNF agents alone was not associated with increased risk of HZ.

The second study [5] was conducted to determine the safety of herpes zoster vaccination (HZV) among IBD patients on anti-TNF medications. Among 56,417 IBD patients followed, a total of 59 were on anti-TNF medication when they were administered HZV. Of these, 12 (20%) were also taking a thiopurine. No cases of either acute varicella or herpes zoster were observed in the 42 days after HZV administration. Thus, the authors concluded it was probably safe to vaccinate patients while on anti-TNF therapy.

The third study [6] was conducted to determine the impact of anti-TNF therapy and other factors on the clinical course of HZ. In this study, the authors found that exposure to anti-TNF therapy was not associated with the risk of having severe HZ in unadjusted analysis and in multivariable logistic regression analysis compared to exposure to mesalamine alone.


The data from these studies put forward several important concepts: 1) IBD patients, even without exposure to immunosuppressive medications, are at increased risk of developing HZ; 2) this risk is increased by immunosuppressive medications and disease flares; 3) exposure to anti-TNF agents at the time of developing HZ is not associated with a more severe manifestation of the disease; 4) finally, it appears that it is safe to administer HZV while a person is on anti-TNF therapy, but clinical considerations should be kept in mind. With an aging IBD population and the advent of new drugs to treat the disease that may be associated with an increased risk of HZ, these studies add to the existing body of knowledge in this field.

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1. Schmader K. Herpes Zoster in Older Adults. Clin Infect Dis. 2001;32:1481–1486.

2. Cohen JI. Clinical Practice: Herpes Zoster. New Engl J Med. 2013;369:255-263. doi:10.1056/NEJMcp1302674.

3. Rimland D, Moanna A. Increasing incidence of herpes zoster among veterans.Clin Infect Dis. 2010;50:1000-1005

4. Khan N, Patel D, Trivedi C, Shah Y, Lichtenstein G, Lewis J, Yang YX. Overall and Comparative Risk of Herpes Zoster With Pharmacotherapy for Inflammatory Bowel Diseases: A Nationwide Cohort Study. Clin Gastroenterol Hepatol. 2017;Jan 5. pii: S1542-3565(18)30012-0. doi: 10.1016/j.cgh.2017.12.052.

5. Khan N, Shah Y, Trivedi C, Lewis JD. Safety of herpes zoster vaccination among inflammatory bowel disease patients being treated with anti‐TNF medications. Aliment Pharmacol Ther. 2017;46:668-672.

6. Khan N, Trivedi C, Shah,Y, Patel D, Lewis J, Yang YX. The Severity of Herpes Zoster in Inflammatory Bowel Disease Patients Treated With Anti-TNF Agents. Inflammatory bowel diseases. Inflamm Bowel Dis. 2018 Mar 7. doi: 10.1093/ibd/izx115.

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