Lyme Vaccine Fears
Concerns newly approved drug can cause arthritis
By Ridgely Ochs
Staff Writer
Newsday.com News, March 9, 2000
LYME DISEASE VACCINATIONS led to 298 reports of adverse reactions last year,
the first year the vaccine was on the market, according to reports to the
Food and Drug Administration obtained by Newsday under the Freedom of
Information Act. Of those, about 10 percent reported symptoms of chronic
arthritis, which some doctors and scientists fear could be a potential side
effect of the vaccine.
The theoretical possibility of the vaccine's prompting such an autoimmune
response, in which the body attacks its own tissue, was known to the
scientists, drug makers and the FDA before the vaccine was approved, although
it is not included in the warning label.
[Photo by Tom Forschner and Karen Vanderhoof-Forschner]
"I'm stunned. Looking at these data, I'm highly concerned by the number of
the reactions and the severity of the reactions," said Karen
Vanderhoof-Forschner, chairwoman of the board of directors of the nonprofit
Lyme Disease Foundation
in Hartford. Vanderhoof-Forschner testified in May, 1998, before the FDA
advisory panel urging the vaccine's approval by the FDA. "This is a voluntary
reporting system, so this is probably the tip of the iceberg. How is the
public supposed to evaluate this data?"
Most of the other events reported--a very small number of the 600,000
people who took the vaccine in its first year--appear to be allergic
reactions, some quite severe, or failures of the vaccine to work. About
one-third of the patients who had a reaction ended up in the emergency room.
Both the FDA and SmithKline Beecham Pharmaceuticals of Philadelphia, maker of
the vaccine marketed as LYMErix, say that the reports of adverse events don't
raise any red flags.
An FDA spokeswoman, Lenore Gelbsaid the reports are not proof the adverse
events were caused by the vaccine. "If we do have concerns, we make an effort
to change the labeling to reflect that ... There is no effort to change the
label," she said. She declined to comment further.
Dennis Parenti, group director of adult vaccines for SmithKline Beecham, said
600,000 people got the vaccine in 1999, after it was approved in December,
1998; 20,000 more had participated in trials testing it, and there is no
evidence of an increase in arthritis because of it.
"We've sliced it and diced it and every way looked at it and repeated some
tests, and we and the FDA found there was no association," Parenti said.
But several lawsuits, including a class action suit in Pennsylvania, have
been filed against SmithKline Beecham alleging the vaccine can cause
arthritis in some people. The suit charges that the drug-maker failed to warn
doctors and the public that LYMErix exposes people of a certain genetic
type--20 to 30 percent of the population--"to the risk of a chronic,
degenerative
and incurable autoimmune disease which is much greater than the risk posed to
these individuals by an ordinary Lyme-carrier tick bite."
The suit wants the company to relabel its vaccine, warn the public and tell
doctors to screen for those who might be susceptible to a reaction. And it
wants the drug manufacturer to create a trust fund to pay for blood tests for
those who already have had the vaccine to see if they are at risk.
"There is a lot of smoke here, and underneath we believe there is a fire.
This is a chance for SmithKline Beecham to do the right thing and do it early
on their liability," said Albert Brooks of Sheller, Lugwig & Bader of
Philadephia,
which filed the suit.
A New Jersey minister, Zelma Johnson, is also in the process of filing a
lawsuit against the drug company alleging that the vaccine caused her
arthritis.
Ira Maurer, a White Plains lawyer representing Johnson as well as three
others who were in the clinical trials for the vaccine, said, "You go under
the assumption that side effects will be the typical aches and pains, but
when you look at these reports [of adverse events], many are far more
serious."
All drugs have potential side effects that may not show up until used in a
large population. What is unusual about this vaccine is that the chief
researcher, the drug company, the FDA advisory panel that recommended its
approval and the FDA knew beforehand there was the theoretical possibility
this one could lead to arthritis.
The question, some say, is whether the risks of the vaccine's side effects
outweigh the potential benefits.
"I wouldn't take the vaccine," said Ronald Schell, a Lyme disease researcher
from the University of Wisconsin. "I recognize that's a prejudice based on my
animal research." He recently published a study that found hamsters injected
with the vaccine were more likely to get arthritis.
"I want people to be aware; they should know of the potential [to cause
arthritis]. Right now, there's a lack of choice," said Dr. Charlene DeMarco,
an emerging-diseases specialist in Egg Harbor, N.J., who has served as a
consultant in the class action suit. DeMarco believes people who carry a gene
that may predispose them to an autoimmune response should be warned before
getting the vaccine.
The vaccine works by stimulating the immune system to produce antibodies to a
protein found on the outer surface of the bacterium B. burgdorferi, which
causes Lyme disease.
But the lead researcher for the SmithKline vaccine, Dr. Allan Steere of New
England Medical Center in Boston, knew--and indeed published the fact six
months before the vaccine was approved--that a part of that outer-surface
protein, called OspA, has the potential of inducing a "cross-reaction" with a
human protein (hLFA-1) in about 20-30 percent of the population (those people
who have the HLA-DR4 gene). Cross-reacting means that in these people, the
body's immune system could attack the human protein, thinking it was part of
an invading bacterium. Some experts think it is this part of the bacterium
that induces so-called Lyme arthritis, which resembles rheumatoid arthritis.
Steere's study, published in the journal Science in July, 1998, was a test
tube study, not proof it could occur in humans. But it has added fuel to
concern about the possibility.
In it, three groups of four to seven hamsters each were given different doses
of a Lyme vaccine suspended in aluminum hydroxide. The vaccine was not
LYMErix but was very similar to it. Seven others were injected with a
commercially available canine version of the vaccine. A group of
nonvaccinated hamsters and a group injected with just aluminum hydroxide were
comparison groups.
All were then infected with the Lyme bacteria.
All the vaccinated hamsters developed "severe destructive Lyme arthritis;" in
some groups 100 percent of the vaccinated hamsters were afflicted. By
comparison, none of the unvaccinated hamsters developed higher than normal
levels of arthritis typical of hamsters with Lyme disease.
The study, published last month in the journal Infection and Immunity, has
caused a stir among Lyme experts. In fact, Schell initially refused to
discuss the article, saying it was "too political." But he and his colleagues
state unequivocally in the study:
"Recently the Food and Drug Administration approved the use of OspA for
vaccination of humans despite indirect evidence and concerns that OspA is
associated with arthritis. In this study, we present direct evidence that
vaccination ... can induce severe destructive arthritis in hamsters after
challenge with the Lyme borreliosis spirochete." Schell says his study does
not prove the vaccine can induce arthritis in people, but "it raises the
flag, and I am concerned."
While Schell was reluctant to discuss his findings, others were quick to
assail them. Dr. Neal Halsey, director of Johns Hopkins University's
Institute of Vaccine Safety, questioned the study's relevance, saying that
hamsters are prone to develop arthritis and that the vaccine used was not
LYMErix.
Schell countered that hamsters are not particularly prone to arthritis.
"There's no evidence of that in the literature," he said. And he said he
avoided using LYMErix in the study "for political reasons." His own
formulation was different by "one amino acid."
But Halsey and others said that animal studies are not as significant as the
results of clinical trials in humans. Halsey was head of the data monitoring
and safety board for the SmithKline vaccine trials.
In that trial of 10,936 people begun in 1995, most side effects were minor,
and only about 1 percent of those vaccinated and 1 percent of those in the
placebo group developed arthritis, Halsey said. A trial of 10,305 of a
similar vaccine made by Pasteur Merieux Connaught of Swiftwater, Pa.--never
brought for FDA approval--showed similar results.
"No way would I have gone on to the pediatric studies if I had seen anything
in the study to show there were worries," he said.
Members of the FDA's advisory panel also said the data they saw showed no
pattern of serious side effects in the clinical trial vaccine.
"The advisory panel was aware of the theoretical risk of this vaccine causing
autoimmunity. A careful evaluation of study patients did not reveal any
problems, but the panel recommended the vaccine be monitored post-approval to
see if anything occurred as greater numbers were vaccinated," said panel
member Raymond Dattwyler, director of the Lyme disease research center at the
State University of New York at Stony Brook.
"Regarding cross-reactivity, we were all very aware, and we looked at it very
carefully," said Kathyrn Edwards, a vaccinologist at Vanderbilt University in
Nashville and a panel member. "I think we take the very best data we can; we
think about it very seriously ... No one has a crystal ball."
Dr. Leonard Sigal, chief investigator for the Connaught vaccine trial, said
there were no untoward side effects in his study. "Cross-reactivity wasn't
seen in the Connaught trial under very controlled conditions."
But there were signs that some participants felt they were having bad
reactions.
Before the vaccine was approved, at least four lawsuits were filed by people
who had participated in the vaccine trials -- highly unusual since
participants sign informed consents. Three were filed against Connaught; the
other was filed against SmithKline. In two of the Connaught suits and the
SmithKline case, the participants said they had had debilitating
arthritic-like problems. One case was settled for an undisclosed amount,
another dropped and two are pending, said Maurer, the lawyer in those suits.
And others who have experience with the vaccine since its approval are sure
it has done them more harm than good, regardless of the clinical studies.
An East Northport woman who did not want to be identified decided to have her
son, 16, get the vaccine after the repeated urging of his doctor. He had been
diagnosed with Lyme disease in January, 1998. Now she thinks it has made his
knee swell, sidelining the promising track star at a time when colleges are
looking to offer athletic scholarships.
"Had I known then what I know now, I never would have let him have it," the
mother said.
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