The Safety and Immunologic Effectiveness of the Live Varicella-Zoster Vaccine in Patients Receiving Tumor Necrosis Factor Inhibitor Therapy : A Randomized Controlled Trial.

BACKGROUND

The safety and effectiveness of live virus vaccines, such as the varicella-zoster vaccine, are unknown in patients with inflammatory diseases receiving immunomodulatory therapy such as tumor necrosis factor inhibitors (TNFis).

OBJECTIVE

To evaluate the safety and immunogenicity of the live attenuated zoster vaccine (ZVL) in patients receiving TNFis.

DESIGN

Randomized, blinded, placebo-controlled trial. (ClinicalTrials.gov: NCT02538341).

SETTING

Academic and community-based rheumatology, gastroenterology, and dermatology practices.

PATIENTS

Adults aged 50 years or older receiving TNFis for any indication.

INTERVENTION

Random assignment to ZVL versus placebo.

MEASUREMENTS

Glycoprotein enzyme-linked immunosorbent assay (gpELISA) and enzyme-linked immunosorbent spot (ELISpot) from serum and peripheral blood mononuclear cells measured at baseline and 6 weeks after vaccination. Suspected varicella infection or herpes zoster was clinically assessed using digital photographs and polymerase chain reaction on vesicular fluid.

RESULTS

Between March 2015 and December 2018, 617 participants were randomly assigned in a 1:1 ratio to receive ZVL ( = 310) or placebo ( = 307) at 33 centers. Mean age was 62.7 years (SD, 7.5); 66.1% of participants were female, 90% were White, 8.2% were Black, and 5.9% were Hispanic. The most common TNFi indications were rheumatoid arthritis (57.6%) and psoriatic arthritis (24.1%); TNFi medications 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 6, 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 6 weeks, compared with baseline, the mean increases in geometric mean fold rise as measured by gpELISA and ELISpot were 1.33 percentage points (CI, 1.17 to 1.51 percentage points) and 1.39 percentage points (CI, 1.07 to 1.82 percentage points), respectively.

LIMITATION

Potentially limited generalizability to patients receiving other types of immunomodulators.

CONCLUSION

This trial informs safety concerns related to use of live virus vaccines in patients receiving biologics.

PRIMARY FUNDING SOURCE

The National Institute of Arthritis and Musculoskeletal and Skin Diseases and the American College of Rheumatology.