The live zoster vaccine provided optimal safety and efficacy in patients receiving tumor necrosis factor inhibitor (TNFi) biologic therapies for various indications, according to new study results presented at the American College of Rheumatology’s Annual Meeting.1

Increasing evidence has suggested that the risk of herpes zoster is elevated in patients with autoimmune and inflammatory diseases. Previous studies have pointed to the association between herpes zoster and several rheumatic diseases in patients taking specific immunosuppressive medication.2 Shingles typically manifests in patients as a painful blistering rash that lasts a few weeks, and serious complications such as disseminated disease, eye involvement, and even strokes can occur.

To prevent herpes zoster, patients can receive 1 of 2 FDA-approved vaccinations: zoster vaccine live (Zostavax, Merck), which was approved in 2006 for patients age 60 years and older; and the newer, recombinant zoster vaccine (Shingrix, GSK), which was approved in 2017 for adults age 50 years and older. However, the safety and efficacy of live virus vaccines have been questioned in patients taking biologic therapies.

“While the need for prevention in patients with rheumatic diseases is compelling, use of any weakened (attenuated) live virus vaccine is potentially a safety risk,” lead author Jeffrey R Curtis, MD, MS, MPH, professor of medicine at the University of Alabama at Birmingham’s Division of Clinical Immunology and Rheumatology, said in a press release.3 “There is a theoretical risk that a live virus vaccine could give a patient the weakened form of infection. A major goal of the trial was to understand the safety of this live virus vaccine, and to see if it caused infection in any of the participants.”

The Varicella Zoster Vaccine (VERVE) study evaluated the safety and immunogenicity of the live attenuated zoster vaccine in more than 600 US patients receiving TNFis for multiple indications.  

Eligible patients were at least age 50 years, were current users of TNFi therapies, and had no prior zoster vaccination. Fifty-nine percent of patients had rheumatoid arthritis (RA) and 24.5% had psoriatic arthritis (PsA). Patients were taking a variety of TNFis, including adalimumab, infliximab, etanercept, golimumab, and certolizumab. Concomitant therapies included background methotrexate and oral glucocorticoids.

Following vaccination, follow up for safety occurred over a 6-week period, which is the specified risk window for vaccine-related infections that may occur, according to the FDA. The researchers collected polymerase chain reaction (PCR) data with subtyping to differentiate wild-type versus vaccine-related infection, as well as serum and peripheral blood mononuclear cell (PBMC) samples at baseline and week 6 to assess zoster-related immunity. Continued safety follow-ups were conducted through 6 months after vaccination, at which time the patients were unmasked to treatment arm, according to the study.

Overall, the results did not identify any confirmed disseminated or local varicella infection through week 6, either wild-type or vaccine strain, yielding an upper bound of 95% confidence interval for vaccine-relate varicella infection of <1%.

Eight patients developed a rash, but none were positive for varicella infection when tested, according to the study.

“The clinical significance of the trial is to provide high quality direct evidence of the safety of this live virus vaccine in patients who previously were warned not to use it because of the theoretical risk for it to cause infection,” Curtis said in a press release.

According to Curtis, the results may also have implications for the use of other live virus vaccines in TNFi users. Additionally, he noted that further research should evaluate the new adjuvanted shingles vaccine, and that a trial of the new vaccine is being planned for patients with RA and inflammatory bowel disease for 2020.


REFERENCES
  1. Curtis J, Bridges SL, Cofield SS, et al. Results from a randomized controlled trial of the safety of the live varicella vaccine in TNF-treated patients [Abstract number: 824]. Presented at: 2019 ACR/ARP Annual Meeting. November 10, 2019. https://acrabstracts.org/abstract/results-from-a-randomized-controlled-trial-of-the-safety-of-the-live-varicella-vaccine-in-tnf-treated-patients/
  2. Yun H, Yang S, Chen L, et al. Risk of herpes zoster in auto-immune and inflammatory diseases: implications for vaccination. Arthritis Rheumatology. 2016. doi: 10.1002/art.39670
  3. Live Zoster Vaccine Safe and Effective for People Taking TNF Inhibitors [news release]. American College of Rheumatology’s website. https://www.rheumatology.org/About-Us/Newsroom/Press-Releases/ID/1056. Accessed November 11, 2019.