Update on Herpes Zoster (Shingles) Vaccine for Autoimmune Disease Patients

September 21, 2012

The updated American College of Rheumatology recommendations for the management of rheumatoid arthritis include revised information on the use of the live zoster vaccine. In July 2012, an observational study funded by the Agency for Healthcare Research and Quality was published in the Journal of the American Medical Association, providing new evidence on the safety and effectiveness of the vaccine in patients with autoimmune conditions, including RA. This Hotline will summarize this information and is intended as an update to the previous Hotline “Herpes Zoster (Shingles) Vaccine Guidelines for Immunosuppressed Patients,” released on August 1, 2008.

Shingles: Shingles is a reactivation of latent varicella zoster virus (VZV) that typically affects older adults. The lifetime risk of shingles is about 1 in 3. It can be complicated by post-herpetic neuralgia (up to 20%) or even more severe manifestations such as H. zoster opthalmicus or disseminated infection.

The Vaccine: A live, attenuated vaccine (Zostavax), approved in 2006, is recommended for use in healthy patients ≥ 60. The Shingles Prevention Study, which led to FDA approval, found that the vaccine reduced the incidence of shingles by 51% and post-herpetic neuralgia by 67%.1 The number of patients needed to treat (NNT) with the vaccine to prevent 1 case of shingles each year was 175. In March 2011, the FDA extended approval of this vaccine to include healthy patients age 50-59, based on a large study showing that  the vaccine reduced the incidence of shingles by 70% in this group 2.  Because the vaccine is live, there is theoretical concern that immunosuppressed patients may be at risk for infection related to vaccination, particularly in the first few weeks. Patients with autoimmune diseases, or requiring immunosuppression, were excluded from the vaccine trials described above, leading to uncertainty regarding the safety and effectiveness of the vaccine in these individuals. The CDC recommended in 2008 that patients receiving immunosuppression and biologic agents should not receive the vaccine.

The vaccine costs approximately $200 and is covered by most insurance companies for individuals ≥50. For Medicare patients, the vaccine is a part D (pharmacy) benefit, and out-of-pocket costs may be as little as $20. The vaccine can be given in many states by an immunization pharmacist and does not require a physician’s order/prescription. Patients may not be explicitly or accurately screened for autoimmune conditions or biologic medication use.

2012 ACR Recommendations for RA Patients: The updated ACR Recommendations for Use of Non-biologic and Biologic DMARDs in RA3 included new guidance regarding vaccination. RA patients are advised to receive the shingles vaccine prior to initiating non-biologic DMARD or biologic therapy, or if already taking non-biologic DMARDs. However, vaccination with the shingles vaccine is “not recommended” (i.e., considered inappropriate) for patients currently using biologic therapy. This recommendation was evidence level C (largely based upon expert opinion).

New information on the zoster vaccine: The recent observational study 4 examined data on 463,541 Medicare enrollees ≥ age 60 with autoimmune diseases, including RA (~60%), spondyloarthropathies, psoriasis and inflammatory bowel disease. Consistent with a prior report from a large commercial U.S. health plan, investigators found that <5% of patients had ever received the zoster vaccine. 5 Among those not receiving oral steroids, the rate of zoster in unvaccinated patients ranged from 10 to 17 cases per 1000 patient years, depending on concomitant medications. Prednisone and other steroids further increased the risk for zoster by approximately 1.8 fold. Among patients receiving biologics, non-biologic DMARDs, or steroids, the absolute rate difference in those receiving the zoster vaccine was 7.0 per 1000 patient years, yielding a NNT of 142. This absolute rate reduction and NNT is comparable with the Shingles Prevention Study.  An 80% relative reduction in the risk of post-herpetic neuralgia was observed.

Of note, 633 people were exposed to biologic therapies around the time they received the vaccine, most of who (n=551) were users of anti-TNF biologics. The vast majority of these patients were given the vaccine by non-rheumatologists (e.g. primary care physicians). During the next 6 weeks, the time frame in which any safety concerns would have been expected, there was no increased risk found for zoster or primary varicella infection. This preliminary evidence suggests the possibility that the vaccine might be safe to give to patients receiving treatment with biologics.  Further prospective trials of shingles vaccination in patients with autoimmune disease are indicated.

Bottom Line:

• Patients with RA and other autoimmune conditions have a 1.5 to 2 fold increased risk for shingles compared to the general population.
• The CDC recommends Zostavax) for healthy older adults age ≥60.  Newly published guidance from the ACR recommends the vaccine for older RA patients receiving non-biologic DMARD therapies, or before DMARD or biologic treatments are started. The CDC has recommended that individuals receiving lower dose prednisone (< 20 mg/day) or methotrexate and azathioprine at doses used for rheumatic diseases may safely receive the vaccine. The CDC recommendations may be found here.
• The vaccine is currently considered inadvisable for patients treated with biologic therapies. For these patients, it may be reasonable to hold the biologic for a period of time, vaccinate, and resume the biologic approximately 30 days later. However, patients may be reluctant to do this given concerns for disease flare during the time that the biologic is being held.
• Recent observational data suggests that the effectiveness of the zoster vaccine in a large group of patients with autoimmune diseases, including RA and spondyloarthropathies, is comparable to that in healthy, older patients. In the same study, the vaccine was not associated with short term risks for zoster or varicella, even in patients exposed to biologics around the time they were vaccinated. However, in the absence of a prospective trial, this evidence should not be presumed to supersede the cautions above regarding live virus vaccines in biologic users.
• The duration of long-term immunity conferred by an episode of shingles or the zoster vaccine is not clear6, so it may be reasonable to vaccinate even people who have had shingles in the past (e.g. >= 5 years ago).

Hotline Coauthors: Jeffrey R. Curtis, MD, Kenneth G. Saag, MD, Kevin Winthrop, MD
Hotline Editors: Arthur Kavanaugh, MD, and Eric Ruderman, MD.
Disclosures: Drs. Curtis, Saag and Winthrop have received funding from the ACR Within Our Reach program to plan a prospective trial of the zoster vaccine in patients with rheumatoid arthritis and other inflammatory conditions; they have no other disclosures. Dr. Ruderman: nothing to disclose. Dr. Kavanaugh: nothing to disclose.

This Hotline has been reviewed by the editors, the ACR Executive Committee and the Communications & Marketing Committee.

The ACR Hotline is provided by the ACR Communications and Marketing Committee as a service to members. This Hotline reflects the views of the editors and does not represent a position statement of the American College of Rheumatology.

Bibliography

1. Oxman MN, Levin MJ, Johnson GR, et al. A vaccine to prevent herpes zoster and postherpetic neuralgia in older adults. N Engl J Med. Jun 2 2005;352(22):2271-2284.
2. Schmader KE, Levin MJ, Gnann JW, Jr., et al. Efficacy, safety, and tolerability of herpes zoster vaccine in persons aged 50-59 years. Clin Infect Dis. Apr 2012;54(7):922-928.
3. Singh JA, Furst DE, Bharat A, et al. 2012 update of the 2008 American College of Rheumatology recommendations for the use of disease-modifying antirheumatic drugs and biologic agents in the treatment of rheumatoid arthritis. Arthritis Care Res (Hoboken). May 2012;64(5):625-639.
4. Zhang J, Xie  F, Delzell E, et al. Association between vaccination for herpes zoster and risk of herpes zoster infection among older patients with selected immune-mediated diseases. JAMA. Jul 4 2012;308(1):43-49.
5. Zhang J, Delzell ES, Xie F, et al. The use, safety and effectiveness of herpes zoster vaccination in individuals with inflammatory and autoimmune diseases: a longitudinal observational study. Arthritis Res Ther. Oct 24 2011;13(5):R174.
6. Schmader K, Oxman M, Levin M, et al. Persistence of the Efficacy of Zoster Vaccine in the Shingles Prevention Study and the Short-Term Persistence Substudy. Clin Infect Dis. Jul 24 2012.