ACIP Releases Recommendations for Use of Herpes Zoster Vaccines

The Centers for Disease Control and Prevention (CDC) recently released recommendations made by the Advisory Committee on Immunization Practices (ACIP) for the use of herpes zoster (shingles) vaccines.

About 1 million individuals are infected with herpes zoster each year in the United States and the best protection against the virus remains vaccination. With the US Food and Drug Administration’s (FDA) approval of GlaxoSmithKline’s Shingrix on October 20, 2017, there are now 2 vaccines against the virus available on the market.

Shingrix, the Zoster Vaccine Recombinant, Adjuvanted (RZV), is a 2-dose, subunit vaccine containing recombinant glycoprotein E in combination with a novel adjuvant, AS01_B. The other vaccine, Merck’s Zostavax, or Zoster Vaccine Live (ZVL) was approved in 2006.

To create their recommendations, ACIP members reviewed data pertaining to the effectiveness of each vaccine in providing protection against herpes zoster as well as each vaccine’s cost-effectiveness. The recommendations were published in the CDC’s Morbidity and Mortality Weekly Report.

The effectiveness of RZV in preventing herpes zoster was assessed in a 2-part, phase 3 multicenter clinical trial which included over 30,000 participants randomized into 2 arms: those receiving the vaccine and those receiving placebo. The median follow-up time was 3.2 years for those participants who were 50 or older, and 3.7 years for those participants who were 70 or older. Investigators found that the vaccine was 96.6% effective in individuals between the ages of 50 and 59, 97.4% effective in those aged 60 to 69, and 91.3% effective in those 70 or older. Furthermore, vaccine efficacy in the first year after vaccination was 97.6% and 84.7% or higher 3 years after vaccination in those 70 or older.

Two randomized clinical trials and 7 observational studies evaluated the effectiveness of ZVL in preventing herpes zoster infections. A randomized clinical trial that enrolled individuals between 50 and 59 years of age found the vaccine to be 70% effective, while another randomized trial found the vaccine to be 64% effective in those aged 60 and older, and 38% effective in those aged 70 or older. The authors noted a “substantial decrease” in effectiveness following the first year post-vaccination. By 6 years post-vaccination, vaccines effectiveness falls to less than <35%.

In terms of cost-effectiveness, a CDC analysis conducted from a societal perspective over a lifetime found that “under most assumptions, vaccination with RZV prevented more disease at lower overall costs than did vaccination with ZVL,” the authors write. More information on the cost per quality-adjusted life year (QALY) is available in the study.

Taking into consideration available information, ACIP members approved the following recommendations at the October 2017 meeting:

• RZV is recommended for immunocompetent adults 50 years of age or older (14 voted in favor, 1 opposed)
• RZV is recommended for immunocompetent adults who had been previously vaccinated with ZVL (12 voted in favor, 3 opposed)
• RZV is preferred over ZVL (8 voted in favor, 7 opposed)

Some additional important takeaways from the report include:

• RZV can be used in adults aged 50 or older regardless if they received the varicella vaccine or ZVL in the past. Screening for a history of chickenpox is unnecessary. For immunocompetent adults aged 60 or older, ZVL is still recommended for the prevention of herpes zoster.
• The second dose of RZV should be administered 2 to 6 months after the first dose. If more than 6 months have elapsed since the first dose, the vaccine series does not need to be restarted, although alternative dosing regimens have yet to be evaluated. Therefore, individuals may be at risk for herpes zoster during a longer than recommended interval between doses. If the second dose of RZV is administered <4 weeks after the first dose, the second dose should be repeated. Two doses of RZV are necessary regardless of a history of herpes zoster or having had received ZVL in the past.
• To determine when to vaccinate with RZV in those who have previously been vaccinated with ZVL, age and time since receipt of ZVL should be considered. “Clinical trials indicated lower efficacy of ZVL in adults aged 70 years and older; therefore, a shorter interval may be considered based on the recipient’s age when ZVL was administered,” the authors write. RZV should not be given less than 2 months after ZVL.
• Recombinant and adjuvanted vaccines, such as RZV, can be administered concomitantly, at different anatomic sites, with other adult vaccines.
• Providers should discuss expected systemic and local reactogenicity with recipients prior to vaccination. Those who experience a grade 1-3 reaction after the first dose of RZV are still encouraged to complete the series.

Finally, adults with a history of herpes zoster should still receive RZV; however, not while experiencing an episode. Those with chronic medical conditions such as chronic renal failure and diabetes mellitus, those taking low-dose immunosuppressive therapy and those anticipating immunosuppression or who have recovered from an immunocompromising illness should also receive RZV. Those with a history of severe allergic reaction should not receive RZV.

As more data become available, ACIP will review and revise recommendations accordingly.