Live varicella-zoster vaccine effective, 'can be safely used' with TNF inhibitors
The live attenuated varicella-zoster vaccine is safe and provides “reasonable short-term” effectiveness in patients receiving TNF inhibitors for a variety of indications, according to data published in the Annals of Internal Medicine.
“To treat a broad range of chronic autoimmune and inflammatory diseases, including rheumatoid arthritis, psoriasis and psoriatic arthritis, spondyloarthritis, and inflammatory bowel disease (Crohn’s disease and ulcerative colitis), TNF inhibitors (TNFis) are indicated,” Jeffrey R. Curtis, MD, MS, MPH, of the University of Alabama at Birmingham, and colleagues wrote.
“Compared with the general population, patients with these conditions are at higher risk for varicella-zoster virus (VZV) reactivation (shingles) due to their underlying disease states and commonly used immunosuppressive treatments, such as glucocorticoids; thus, prevention of [herpes zoster (HZ)] in these populations is a high priority,” they added. “Despite the demonstrated efficacy and safety of [live attenuated zoster vaccine (ZVL)] in healthy adults aged 50 years or older, no prospective data have examined the safety or the immunologic effectiveness of ZVL in patients receiving TNFis.”
To analyze the safety and immunogenicity of the live attenuated zoster vaccine in patients treated with TNF inhibitors, Curtis and colleagues conducted a randomized, blinded, placebo-controlled trial. Participants included 617 adults aged 50 years or older — recruited from 33 academic and community-based rheumatology, gastroenterology and dermatology practices — receiving TNF inhibitors for any indication. Between March 2015 and December 2018, these participants were randomly assigned 1:1 to receive either the live attenuated zoster vaccine or a placebo. In all, 310 patients received the vaccine.
All participants were followed in the blinded phase until month 6, when the clinical sites and the patients were unblinded. Participants in the vaccine group were followed in the unblinded phase for 1 year. Measurements included glycoprotein enzyme-linked immunosorbent assay (gpELISA) and enzyme-linked immunosorbent spot (ELISpot) from serum and peripheral blood mononuclear cells, both taken at baseline and 6 weeks following vaccination. The researchers assessed suspected varicella infection or herpes zoster using digital photographs and polymerase chain reaction on vesicular fluid.
The most common indications for TNF inhibitors among the participants were RA, at 57.6%, and PsA, 24.1%. Among the patients, 32.7% received adalimumab (Humira, AbbVie), 31.3% were treated with infliximab (Remicade, Janssen), 21.2% received etanercept (Enbrel, Amgen), 9.1% received golimumab (Simponi, Janssen) and 5.7% were treated with certolizumab (Cimzia, UCB). In addition, 48% of participants received concomitant methotrexate, while 10.5% were treated with oral glucocorticoids.
According to the researchers, there were no cases of confirmed varicella infection through week 6, with a cumulative incidence of varicella infection or shingles of 0% (95% CI, 0% to 1.2%). At 6 weeks, the mean increases in geometric mean fold rise, as measured by gpELISA and ELISpot, were 1.33 percentage points (95% CI, 1.17-1.51) and 1.39 percentage points (95% CI, 1.07-1.82), respectively, compared with baseline.
“Although vaccine-induced IgG responses were robust, we found cell-mediated responses to be more variable and not sustained at 1 year after vaccination,” Curtis and colleagues wrote. “Our data suggest that this vaccine, although historically contraindicated in those using TNFis, can be safely used in this setting; however, its long-term efficacy in such patients is unknown.”
The researchers also noted that the immunogenicity data suggested that these patients may require additional evaluations for booster vaccination.
“Results from this study suggest that ZVL was safe and had reasonable short-term effectiveness (based on the 6-week immunogenicity results) in participants receiving TNFis for a broad range of indications,” Curtis and colleagues wrote. “Although country-specific labeling requirements may continue to discourage use of a live virus vaccine in immunosuppressed patients receiving biologic therapies, use of this ZVL in TNFi-treated patients may be a reasonable option, especially in the absence of an alternative zoster vaccine.”