By Alex Otto in the January 200l issue of PHARMACY TODAY

SmithKline Beechan To Defend Vaccine In Class Action Suit

Concerns are growing that SmithKline Beecham's Lyme vaccine (LYMErix) may
cause irreversible autoimmune arthritis in some patients. About 15% of the nea
rly 400 LYMErix adverse events reported to FDA in 1999 involved rheumatologic
symptoms ranging from muscle pain and acing joints to severe arthritis.

The reports suggest that a concern raised in preapproval hearings-the possib-
ility that the vaccine could trigger degenerative autoimmune disease-may not
have been unfounded. Although patients who received the vaccine during trials
were no more likely than others to develop long-term rheumatologic or
neurologic disorders, vaccine recipients were significantly more likely to
report arthralgia and myalgia within 30 days of administration.

SmithKline Beecham stands by the safety of its vaccine, currently the only
one on the market for Lyme disease. "We are aware that this debate is out
there about this theoretical risk," the company told PHARMACY TODAY. "But we
are not seeing any unusual, unexpected patterns," she said, noting that the
rates of rheumatologic disease among LYMErix patients are similar to those
in the general population. The vaccine is about 80% effective in preventing
disease and has been administered to 440,000 patients since its approval in


The concerns about arthritis hinge on human leukocyte antigen DR4 (HLA-DR4),
a surface protein found on white blood cells in about 10% to 30% of the pop-
ulation. It is easily detected by a blood test, but the test costs $300.

A class action lawsuit has been filed against SmithKline by scores of
patients who developed severe arthritis after getting the vaccine. The suit
alleges that LYMErix triggers degenerative autoimmune disease in
HLA-DR4-positive patients and that SmithKline knew of the association before
its vaccine was approved but failed to warn doctors.

The spokesperson denies the charge. "We looked at it in our clinical trials,
specifically at this idea that people who tested positive for the HLA-DR4
were more likely to develop arthritis than anyone else, and found no evidence
of it", she said. The company plans a vigorous defense of its product.

But a handful of rheumatologists are already refusing to give the vaccine to
their patients, among them Andra Gaito, MD, president of the International
Lyme and Associated Diseases Society. Gaito has treated 22 patients who deve
loped severe, crippling rheumatologic disorders following vaccination. A
colleague of hers at Yale has treated 40 such patients.

"The rheumatology community was suspicious of this vaccine to begin with,"
 Gaito said. "Before it was ever approved, there were reports published of
autoimmune reactions in rats, mice, and other lab animals. It doesn't seem
limited to DR4 positive patients. There is such a clear-cut problem here that
this (product) needs to come off the market."

In response to such concerns, FDA recently said it would investigate all
cases of vaccine-associated arthritis, a step that indicates heightened
concern. The agency usually only investigates life-threatening vaccine


LYMErix was generally recommended as safe and effective for adults when appr
oved in 1998, but FDA panelists in preapproval hearings were concerned
that it could trigger autoimmune reactions in HLA-DRA4-positive patients.

Two HLA-DR4-positive study patients, did, in fact, develop joint pain that
lasted for months after being immunized. FDA wondered if these cases
pointed to a potential problem and if the clinical trials had been powerful
enough to
detect one if it existed.

"I am not sure that we have the answer to your question," a SmithKline
researcher told the panelists, but the agency was assured that if the vaccine
"induces joint symptoms, it must be a rare phenomenon, much rarer than the
(HLA=-DR4 trait) itself." The idea of testing patients for the trait was
mentioned, but dismissed as "very difficult." Concern about HLA-DR4 status
was deemed more academic than practical, the company researcher argued.

"The concern is more than academic if this vaccine were to be delivered to
millions of people," a FDA panelist shot back. "We don't know for a fact that
the vaccine elicited either one of these episodes of arthritis and
paresthesias, but I think we are all worried about that. I am left with
uncertainties about whether these two cases are in fact a signal of something
that we would have seen if we had been able to follow (patients) longer.