From
Pharmacy Today

Lyme Vaccine Linked to Autoimmune Arthritis
SmithKline Beecham to Defend Vaccine in Class Action Suit

Alex Otto

[Pharmacy Today 7(1):10, 2001. © 2001 American Pharmaceutical Association]

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

The reports suggest that a concern raised in preapproval hearings -- the possibility 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," a company spokesperson 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 Lyme disease and has been administered to 440,000 patients since its approval in 1998.

Deep Questions About Surface Antigens

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 population. 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 Andrea Gaito, MD, president of the International Lyme and Associated Diseases Society. Gaito has treated 22 patients who developed 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 complications.

Preapproval Testimony

LYMErix was generally recommended as safe and effective for adults when approved in 1998, but FDA panelists in preapproval hearings were concerned that it could trigger autoimmune reactions in HLA-DR4-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," an 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."

When Giving IM Shots, Customize Needle Length to Your Patient's Weight

On November 18, the British Medical Journal published an article that might be of particular interest to pharmacists who give immunizations.

Most vaccines should be given intramuscularly, most conveniently in the shoulder, to optimize immune response. However, clinicians don't always use a needle long enough to get the job done.

According to the article, a recent study of 220 adults found that the standard 5/8 inch needle used for flu and other vaccines was too short to penetrate the deltoid fat pad in 17% of men and nearly 50% of women.

Vaccine injected into fat never enters the circulatory system. Instead, it pools and gets broken down by local enzymes. Immune response is poor and antibody titers soon drop.

To solve the problem, author Jane Zuckerman, senior lecturer at the Royal Free and University College Medical School in London, recommended a 1-inch needle in men weighing between 130 and 260 pounds. Women weighing between 130 and 200 pounds may need an inch-long needle, too, and a 1.5-inch needle was recommended for women over 200 pounds. The standard 5/8-inch needle is fine for women under 130 pounds.

Muscle does not contain a lot of pain fibers, so the difference in patient comfort should be minimal. A wider gauge needle, because it dissipates vaccine over a broader area, may cause less redness and swelling.