Treatment with tumor necrosis factor inhibitor (TNFi) biologic therapies is not a barrier to receiving the live zoster virus vaccine to protect against shingles.

That’s according to a presentation at the recent 2019 American College of Rheumatology/Association of Rheumatology Professional Annual Meeting in Atlanta. 

Five different inhibitors of TNF, which occurs in higher levels in the blood and joints of patients with rheumatic conditions, have been approved by the FDA for the treatment of a range of conditions.

The Varicella Zoster Vaccine (VERVE) trial, a randomized, placebo-controlled, blinded trial of live, attenuated zoster vaccine (ZV), was conducted with more than 600 U.S. participants receiving TNFi therapies. University of Alabama at Birmingham–led researchers sought to evaluate safety and efficacy of the vaccine among patients who might be immunocompromised because of their TNFi treatment and other concurrent medications, such as low-dose glucocorticoids.

“Because patients with rheumatic diseases are at higher risk for reactivation of herpes zoster, also known as shingles, prevention of this painful condition is exceedingly important. Shingles manifests in most patients as a painful blistering rash that lasts a few weeks, but serious complications such as disseminated disease, eye involvement and even strokes can occur,” explained lead author Jeffrey R. Curtis, MD, MS, MPH, a professor of medicine at the University of Alabama at Birmingham’s Division of Clinical Immunology and Rheumatology. “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. 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 authors point out that the safety of live-virus vaccines in patients receiving biologic therapies who may be immunocompromised has undergone minimal evaluation. To remedy that, they conducted the VERVE study, a blinded, 1:1 randomized placebo-controlled trial of the live attenuated ZV to evaluate safety and immunogenicity.

To be eligible, participants had to be at least age 50 years, current users of TNFi for any indication, and have received no prior ZV. Researchers followed-up on safety issues for 6 weeks, which is the FDA-specified risk window for vaccine-related infection, were it to occur.

In cases where varicella infection or shingles was suspected, patients underwent clinical assessment, polymerase chain reaction collection (with subtyping to differentiate wild-type vs. vaccine [Oka]-related infection), and digital photographs. 

By the time recruitment closed in December 2018, 617 randomized participants had been recruited at 33 centers. The patients had a mean age of 62.4 years, were 66.9% female, 87.2% white, 8.8% African American, and 4.4% Hispanic. 

The most common TNFi indications for participants included rheumatoid arthritis (59.6%) and psoriatic arthritis (24.5%). TNFi medication received at baseline included: adalimumab (32.7%), infliximab (31.3%), etanercept (21.2%), golimumab (9.1%), and certolizumab (5.7%). 

Patients often received concomitant therapies, including background methotrexate (48.0%), and oral glucocorticoids (10.5%). 

Results indicate that, through Week 6, there were zero cases of confirmed disseminated or local varicella infection, either wild type or vaccine strain, yielding an upper bound of the 95% confidence interval for vaccine-related varicella infection of less than 1%. 

With eight rashes swabbed for varicella PCR, none were positive, and no clinically adjudicated varicella or shingles reactivation cases were observed through Week 6, according to the authors, who add that immunologic effectiveness of ZV will be reported in the full cohort at the end of the year. 

“The randomized VERVE trial comprised of more than 600 patients receiving TNFi for multiple indications observed no cases of vaccine-related varicella infection or reactivation in the 6-week risk period following live zoster vaccination,” researchers concluded. “This trial informs safety concerns of use of live virus vaccines in this population.”

“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 added. “It also opens the door for the idea that for TNFi users, perhaps other live virus vaccines also may be safe and might be considered in certain circumstances. Future directions for this research group are to rigorously study the new adjuvanted shingles vaccine to better understand its safety, tolerability and effectiveness in patients with RA and inflammatory bowel disease, using similar methods. A trial of this new shingles vaccine is being planned for these patients and likely will begin in 2020.”

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