Shingles vaccine safe for immunocompromised patients on TNF inhibitors: VERVE Study

Delhi: Biologic drugs that affect the immune system may interfere with the effectiveness of vaccines and therefore should not be used while patients are being treated with biologics.But live zoster vaccine or shingles vaccine has been found to be safe for use in immunocompromised patients receiving tumour necrosis factor inhibitor (TNFi) biologic therapies, according to a recent study presented at the 2019 ACR/ARP Annual Meeting.

The Varicella Zoster Vaccine (VERVE) study comprised of more than 600 patients receiving TNFi for multiple indications. They fond that in the 6-week risk period following live zoster vaccination, there were no cases of vaccine-related varicella infection or reactivation.

Higher levels of TNF, in the blood of those suffering from rheumatic conditions, leads to inflammation and persistent symptoms. TNF inhibitors are the drugs that help to control inflammation in the joints, gastrointestinal tract, and skin.

There is not much data on the safety of live virus vaccines in patients receiving biologic therapies who may be immunocompromised. Jeffrey Curtis, a professor of medicine at the University of Alabama at Birmingham's Division of Clinical Immunology and Rheumatology, and colleagues conducted the VERVE study -- a blinded 1:1 randomized placebo-controlled trial of the live attenuated zoster vaccine (ZV) in patients receiving TNF inhibitors (TNFi) to evaluate safety and immunogenicity.

"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 manifest 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," said Dr Curtis. "While the need for prevention in patients with rheumatic diseases is compelling, the 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 study involved 617 patients, at least 50 years of age, current users of TNFi for any indication, and no prior ZV. Safety follow-up occurred over 6 weeks (the FDA-specified risk window for vaccine-related infection, were it to occur). Suspected cases of varicella infection or shingles had a clinical assessment, PCR collection (with subtyping to differentiate wild-type vs. vaccine [Oka]-related infection), and digital photographs. The review was conducted under the oversight of an NIH-appointed Data Safety Monitoring Board.

Demographics included an average age of 62 where 66 per cent were women, 87 per cent were white, about nine per cent were African American, and four per cent were Hispanic.

Key findings of the study include:

• Most common TNFi indications: rheumatoid arthritis (59.6%), psoriatic arthritis (24.5%); TNFi medication at baseline: adalimumab (32.7%), infliximab (31.3%), etanercept (21.2%), golimumab (9.1%), certolizumab (5.7%).


• Concomitant therapies included background methotrexate (48.0%), and oral glucocorticoids (10.5%).


• 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 < 1%.


• A total of 8 rashes were swabbed for varicella PCR; none were positive, and no clinically adjudicated varicella or shingles reactivation cases were observed through week 6.

"VERVE will close to blinded follow up in Summer 2019 and immunologic effectiveness of ZV will be reported in the full cohort in November 2019," wrote the authors.

"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," said Dr. Curtis. "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."

"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. This trial informs safety concerns of the use of live virus vaccines in this population," concluded the authors.

Read the abstract of the study "Results from a Randomized Controlled Trial of the Safety of the Live Varicella Vaccine in TNF-Treated Patients".