Jan. 31, 2001 (Washington) -- Could a vaccine be more dangerous than the disease it's supposed to prevent? That question was heavy in the air Wednesday, as the Food and Drug Administration's Vaccines and Related Biological Products Advisory Committee held a special session on the safety of Glaxo SmithKline's Lyme disease vaccine LYMErix.
The panel held the meeting to review reports that indicate the vaccine may somehow trigger treatment-resistant Lyme arthritis and other chronic arthritic disorders.
About two-and-a-half years ago, the same committee had recommended that the FDA approve the vaccine, and panel members said they were frustrated that additional studies have failed to clear up uncertainties about adverse events that may be linked to the vaccine.
In the end, most panel members said they supported revisions and possible new warnings on the vaccine's package inserts, as well as heightened public education about the potential risks of the vaccine.
Lyme disease most commonly affects individuals in New England and the mid-Atlantic states. It's transferred to humans via deer ticks that live in grassy and wooded areas, with May and June being the highest-risk months for transmission. The disease was first recognized in 1975, and the vaccine maker says that it is still on the rise. More than 100,000 cases were reported to the federal government between 1982 and 1998.
Lyme disease isn't life threatening, but its long-term effects can include joints destruction, neurological disorders, and other serious conditions.
The LYMErix vaccine was approved late in 1998 for use in those at least 15 years old. It's been marketed in the U.S. since January 1999, and Glaxo SmithKline says that it has distributed 1.4 million doses, although it acknowledged that fewer patients than expected have actually received the vaccine.
The vaccine series, which is administered in three separate doses, is relatively costly. Each dose costs about $50. Despite the cost, its effectiveness is somewhere less than 80%.
Even as panel members noted that science on the vaccine's safety has not advanced in recent years, they said that anecdotal complaints from patients have increased dramatically. A series of Lyme vaccine recipients and patient advocates made often-emotional presentations to the panel, urging that the vaccine be pulled from the market, that it be put on hold until ongoing safety studies are completed, or that stronger warnings go on the product's labeling.
But a series of researchers from Glaxo SmithKline maintained that the vaccine was unrelated to arthritis or other mysterious conditions, and outlined a set of studies that it has under way. The company says that the product's safety profile hasn't changed since it was approved.
The patients' testimonials clearly had an effect on the advisory committee. In his closing remarks, W. Michael O'Fallon, PhD, an invited participant in the panel's discussion, said, "Would I take the vaccine? No."
Benjamin Luft, MD, another invited participant, cited a "twilight zone" of disconnect in the conflicting accounts of the vaccine recipients and the drug firm.
According to panel member David Stephens, MD, a "huge body of anecdotal data" suggests that "we may be missing something."
Almost 1,000 adverse event reports have been filed on the Lyme vaccine, with around 70 citing arthritis-like side effects. Four deaths also have been reported following administration of the vaccine.
But according to Glaxo SmithKline, the events have taken no particular clinical pattern and "no cluster in time to onset."
According to the FDA, the rates of arthritis suffered by those who've taken the vaccine aren't higher than rates among the general population.
The FDA holds that more adverse events are occurring than are reported, but agrees with the vaccine maker that most of the reported events involve side effects already described in the vaccine's physician labeling.
The company says it has experience with more than 18,000 subjects in controlled investigations, including more than 8,000 post-licensure vaccinees.
Glaxo SmithKline presented animal study data that it claimed supported its position that the vaccine is unrelated to the arthritis. But panel member Steve Kohl, MD, and others said the study was irrelevant to the nature of the possible problem in humans.
The drugmaker also said that it was tracking actual vaccinations as delivered by physicians through three HMOs, so it can closely follow thousands of doses, possible side effects, and follow-up medical care. By the end of the year, said Glaxo researcher Richard Platt, MD, "We will have real information about the relative risks."
But several members of the panel said that they were worried that the study would not be large enough to provide definitive data on the supposed connection between the vaccine and arthritis.
The panel did not hold any formal votes and is not responsible for deciding FDA policy.