Study shows shingles vaccine safe in patients taking TNF inhibitors

The safety and effectiveness of live virus vaccines, such as the varicella-zoster vaccine, have been unknown in patients with inflammatory diseases who are receiving immunomodulatory therapy.

Live attenuated zoster vaccine was not associated with any cases of shingles in patients receiving tumor necrosis factor (TNF) inhibitors, a new study found.

In the VaricElla zosteR VaccinE (VERVE) trial, researchers enrolled adult patients ages 50 years and older from 33 academic and community-based rheumatology, gastroenterology, and dermatology practices who were receiving TNF inhibitors for any indication and randomly assigned them to receive the live attenuated zoster vaccine or placebo. Patients were followed in a blinded manner until month six, when clinical sites and participants were unblinded and followed until year one. The trial began in March 2015 and enrolled patients through December 2018.

Glycoprotein enzyme-linked immunosorbent assay (gpELISA) and enzyme-linked immunosorbent spot (ELISpot) from serum and peripheral blood mononuclear cells were measured at baseline and at six weeks after vaccination. Digital photographs and polymerase chain reaction on vesicular fluid were used to clinically assess suspected varicella infection or herpes zoster. Results of the trial were published Sept. 28 by Annals of Internal Medicine.

Three hundred ten patients were assigned to the live vaccine group, and 307 were assigned to the placebo group. The most common indications for TNF inhibitors were rheumatoid arthritis (57.6%) and psoriatic arthritis (24.1%), and the TNF inhibitors used were adalimumab (32.7%), infliximab (31.3%), etanercept (21.2%), golimumab (9.1%), and certolizumab (5.7%). Concomitant therapies included methotrexate (48.0%) and oral glucocorticoids (10.5%).

Through week six of the trial, no cases of confirmed varicella infection were found. Cumulative incidence of varicella infection or shingles was 0.0% (95% CI, 0.0% to 1.2%). At six weeks, the mean increases in geometric mean fold rise from baseline as measured by gpELISA and ELISpot were 1.33 percentage points (95% CI, 1.17 to 1.51 percentage points) and 1.39 percentage points (95% CI, 1.07 to 1.82 percentage points), respectively.

The authors concluded that the live attenuated zoster vaccine can be safely used in patients taking TNF inhibitors, although it historically has been contraindicated in this setting. They noted that its long-term efficacy in such patients is unknown and that immunogenicity data from their trial indicate a potential need for booster vaccination. “Although country-specific labeling requirements may continue to discourage use of a live virus vaccine in immunosuppressed patients receiving biologic therapies, use of this [live attenuated zoster vaccine] in [TNF inhibitor]-treated patients may be a reasonable option, especially in the absence of an alternative zoster vaccine,” the authors wrote.