ATLANTA – The shingles vaccine Zostavax significantly reduced the incidence of herpes zoster and was generally well tolerated in a randomized, double-blind, placebo-controlled phase III trial involving more than 22,000 adults aged 50-59 years.
However, there was an elevated risk of local reactions with Zostavax among adults in that age group in both Merck’s phase III study and a separate analysis conducted by the CDC. Zostavax has been licensed in the United States for adults aged 60 years and older since 2006, and a supplemental biological license application for the 50- to 59-year age group is now under review by the Food and Drug Administration.
The Merck study enrolled 22,439 varicella history–positive, herpes zoster–negative 50- to 59-year olds who were followed for at least 1 year after receipt of a single Zostavax dose. Subjects were asked to notify investigators if they developed a rash or other symptoms suggestive of shingles. Those reporting signs or symptoms were contacted every 3 days for 21 days for assessment, said Dr. Janie Parrino, director of vaccine clinical research at Merck Research Laboratories.
Two-thirds of the subjects were female, and nearly all (94%) were white. More than 20% had hypertension, while 10%-20% had other medical conditions including hypercholesterolemia, drug hypersensitivity, and seasonal allergy.
There were 30 confirmed cases of herpes zoster among the 11,211 Zostavax recipients, compared with 99 among the 11,228 who got placebo, for a vaccine efficacy of about 70%. Zostavax also elicited a higher varicella zoster virus-specific antibody response, and a demonstrated an estimated 73% relative reduction in mean zoster pain severity-by-duration score, Dr. Parrino reported.
Compared with placebo, Zostavax recipients had a higher overall incidence of adverse events within 6 week postvaccination (73% vs. 42%). Injection-site reactions were reported by 64% vs. 14%, and systemic adverse events – primarily pain in the extremity and headache – by 35% vs. 34%. However, rates of serious adverse events were similar: 0.6% Zostavax vs. 0.5% placebo within 42 days post vaccination and 2.1% vs. 1.9% by 182 days. One Zostavax recipient had an anaphylactic reaction.
Mortality rates were also similar, at 1.18 vs. 1.90 deaths per 1000 person-years in the Zostavax and placebo groups, respectively.
In a separate analysis of 2007-2008 data collected from the CDC’s Vaccine Safety Datalink, local reactions were considerably higher among the 6,832 adults aged 50-59 years who received Zostavax compared with the older age groups. Compared with those receiving placebo, the relative risk for inflammation and/or allergic reaction within 1-7 days of vaccination was 9.5 in the 50- to 59-year age group, compared with 3.0 among 60- to 65-year olds and 1.59 among those aged 70-79.
In the overall study group of 192,467 vaccinees, there were no other increased rates of prespecified conditions, including stroke, cardiovascular events, meningitis, encephalitis, encephalopathy, neurologic conditions, or serious reactions such as cellulitis and infection, said Hung Fu Tseng, Ph.D., of Southern California Kaiser Permanente, a participating site in the Vaccine Safety Datalink.
"The data provide reassurance that the zoster vaccine is generally safe and well tolerated ... The elevated risk of local reaction among the 50- to 59-years group needs further investigation," said Dr. Tseng.
Merck anticipates an FDA response about the 50- to 59-year age group indication by the end of the first half of the year, according to a company spokeswoman.
Dr. Tseng has received research funding from Merck for other vaccine-related studies.