May 2000
ATLANTA - A study of
the Lyme disease vaccine (LYMErix, SmithKline Beecham) in the pediatric
population showed that after two doses, children ranging from 4 to 14 years had
titers similar to those seen in adults who received three doses of vaccine.
The vaccine was administered on a 0-, 1- and 12-month schedule in a large, double-blind trial at 17 sites in the United States to 4,087 children between the ages of 4 and 18 years. The vaccine is currently approved for use among those ages 15 to 70 years.
"The safety profile was similar to what we've already seen in adults," said Dennis Parenti, MD, group director of clinical research and development and medical affairs at SmithKline Beecham, who recently presented the information to the Advisory Committee on Immunization Practices.
Among solicited adverse events, there was a higher incidence of local injection-site reactions, headache, fever, fatigue, arthralgia and influenza-like illness starting on the day of or day after immunization. The adverse events were usually self-limiting, generally lasting two to three days, and the majority were mild to moderate.
"There were no differences in the incidence of adverse events between the two groups after the diary card period," said Parenti. With regard to immunogenicity, data on 4- to 14-year-olds was compared with adults (ages 15 to 70 years) in the efficacy trial.
"Post-dose two, the pediatric study population obtained a titer of >5,000 enzyme-linked immunosorbent assay (ELISA) units/mL with 91% of participants having a sero-protective level >1,400. In the adult study, the titers after two doses were 1,300 ELISA units/mL in approximately one-half of the subjects being sero-protected. After dose three at month 13, the children obtained a geometric mean antibody titer (GMT) of 29,000 with 100% being sero-protected. In the adult efficacy trial, the adults had a titer of 6,000, with 90% being sero-protected."
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The Lyme disease vaccine was licensed on Dec. 21, 1998. According to Ned Hayes, MD, of the Centers for Disease Control and Prevention, more than 1 million doses of LYMErix were distributed between December 1998 and December 1999, and an estimated 500,000 individuals actually received the vaccine. There were 386 adverse event reports during that time and no unexpected patterns of adverse events. The number of these reported adverse events that were in fact caused by vaccination is unknown.
"Of the 386, 163 were in men, 191 were in women and the gender of 32 were unknown," said Hayes. "The preponderance of women has been seen in other reports of adult vaccinees through the Vaccine Adverse Events Reporting System (VAERS). The median age was 50 years, with ages ranging from 15 to 82 years. There were 15 vaccine recipients in the surveillance system that were older than age 70."
Of the 386 adverse event reports, 115 involved an emergency room visit and 20 resulted in hospitalization. Seven were described as life threatening, four were reported as permanent disabilities and there were two deaths. The deaths, however, occurred in a 54-year-old man and a 63-year-old man whose autopsy reports both showed extensive cardiovascular disease, and were probably not related to vaccination, according to Hayes.
The most frequently reported adverse events were myalgia, injection-site reactions, arthralgia, fever, headache, pain, flu-like syndrome, chills and tremors. Time from vaccination to onset of adverse event reported indicated the majority occurred on the day of or day after injection.
"There were 12 reports of arthritis; of those, five had onset three days within vaccination, two were in week two and two were in week three," said Hayes. "The other two had unknown onset days. We didn't think the pattern was particularly concerning. There were eight reports of facial paralysis, one at day zero and one at day two. We were intrigued that four occurred in weeks three to four, one in week eight and one was unknown."
According to Hayes, VAERS data for the first year of the Lyme disease vaccine licensure had no unexpected adverse events. However, he said he would like to see continued surveillance for any unusual patterns of adverse events.
Four studies have been performed to assess the need and timing of booster doses of the vaccine. According to Parenti, in one study approximately 300 subjects out of the original immunogenicity subset of 450 subjects from the efficacy trial received either one or two booster doses. None experienced any serious adverse events related to the booster dose.
In a second study, approximately 450 patients were primed with a 0, 1, 2 schedule and received either one or two booster doses. Two serious adverse events were thought to be related to vaccination.
"If you look at the solicited adverse events immediately after vaccination and compare the data from dose three at month two compared with the first booster at month 12, there is no statistical difference in any of the solicited adverse events," said Parenti.
In an ongoing booster study with approximately 1,200 participants who received their first booster dose in 1999 at month 24 following a 0, 1, 12 primary schedule, preliminary data show no unusual or unexpected pattern of adverse events.
According to Parenti, researchers have 48 months of booster-dose follow-up data on some subjects and month 60 follow-up data from one study will soon be available.
Alternate dosing schedules can provide maximum protection in a shorter period of time, Parenti said, in response to a question. "You can administer the first two doses any time of year, but the important point would be to administer the third dose prior to onset of the season or expected exposure," he noted.
Two studies of dosing on a 0, 1, 6 schedule and a 0, 1, 2 schedule show the vaccine is well tolerated.
"We have proposed to the FDA that a flexible schedule, with the third dose administered prior to the season, is an acceptable alternate schedule," he concluded.
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