• Jeffrey R Curtis, Stacey S Cofield, S Louis Bridges, John Bassler, Atul Deodhar, Theresa L Ford, Joseph Huffstutter, Allen Jankeel, Alan Kivitz, Shaila Kamal, Stephen Lindsey, Ilhem Messaoudi, Norma Mendoza, Kaleb Michaud, Ted R Mikuls, David Ridley, William Shergy, Sarah A R Siegel, and Kevin L Winthrop.
• Division of Clinical Immunology and Rheumatology, The University of Alabama at Birmingham, Birmingham, Alabama (J.R.C., S.K.).
• Ann. Intern. Med. 2021 Nov 1; 174 (11): 151015181510-1518.

BackgroundThe 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).ObjectiveTo evaluate the safety and immunogenicity of the live attenuated zoster vaccine (ZVL) in patients receiving TNFis.DesignRandomized, blinded, placebo-controlled trial. (ClinicalTrials.gov: NCT02538341).SettingAcademic and community-based rheumatology, gastroenterology, and dermatology practices.PatientsAdults aged 50 years or older receiving TNFis for any indication.InterventionRandom assignment to ZVL versus placebo.MeasurementsGlycoprotein 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.ResultsBetween March 2015 and December 2018, 617 participants were randomly assigned in a 1:1 ratio to receive ZVL (n = 310) or placebo (n = 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.LimitationPotentially limited generalizability to patients receiving other types of immunomodulators.ConclusionThis trial informs safety concerns related to use of live virus vaccines in patients receiving biologics.Primary Funding SourceThe National Institute of Arthritis and Musculoskeletal and Skin Diseases and the American College of Rheumatology.

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