Special Feature
Lyme Disease Vaccine — LYMErix (SmithKline Beecham)
By William T. Elliott, MD, FACP, and James Chan, PharmD, PhD
Lyme disease is the most common vector-borne infection in the United States and the incidence is increasing, with more than 16,000 cases annually.1 The disease, caused by the tick-borne spirochete Borrelia burgdorferi, can be found throughout the nation but is particularly concentrated in rural and wooded areas in the Northeast, upper Midwest, and Pacific Northwest.
Work has been ongoing for years to develop a vaccine for this potentially debilitating, multisystem disease and, in December 1998, SmithKline Beecham received approval from the FDA to market the first Lyme disease vaccine (LYMErix). The vaccine contains an immunodominant outer surface protein (OspA) of B. burgdorferi produced by recombinant DNA technology and expressed by E. coli.
Indications
LYMErix is indicated for active immunization against Lyme disease in individuals 15-70 years of age. Safety and efficacy in children has not been established.
Dosage
Primary vaccination consist of 30 mcg/0.5 mL dose given intramuscularly at 0, 1, and 12 months. LYMErix is supplied as single-dose vials and prefilled syringes.
The efficacy for this vaccine is based on administration of the second and third doses several weeks prior to the onset of the Borrelia transmission season in the local geographic area.2
Patients previously infected may also benefit from the vaccine, as such infection may not confer protective immunity.2,3 However, LYMErix should not be administered to patients with treatment-resistant Lyme arthritis, since these patients are immune reactive to OspA.2
Potential Advantages
LYMErix is the first vaccine found to be safe and effective for the prevention of Lyme disease. Efficacy has been shown to be 50% in the first year (after 2 doses) and 78% in the second year (after 3 doses) as defined by clinical and serologic evidence of Lyme disease.2,4 The incidence of disease was reduced from 0.77% to 0.39% the first year and from 1.27% to 0.27% the second year. The efficacy of preventing asymptomatic disease (defined as seroconversion with no clinical symptoms) was 83% the first year and 100% the second year. The incidence of asymptomatic seroconversion was reduced from 0.23% to 0.04% the first year and 0.27% to 0% the second year.2
Potential Disadvantages
The currently approved regimen requires one year to complete. After two doses, the vaccine provides modest protection of 50% (CI, 14-71%). The second year protection after the third dose increased to 78% (59-88%). SmithKline Beecham is studying several shortened regimens, including 0, 1, and 2 months, which may provide optimal protection,5 but the FDA has not approved these regimens. The vaccine has not been approved by the FDA for use in ages younger than 15 years. The percent of reported cases of Lyme disease in this population is 23%.1
The most commonly reported side effects of LYME-rix were injection site pain (22% vs 7% for placebo). Others included chills/rigors (2% vs 0.7%), fever (2.6% vs 1.6%), myalgia (4.8% vs 2.9%), and flu-like symptoms (2.5% vs 1.7%).2
The duration of immunity has not been established,2 and longer-term studies will be needed to determine whether boosters are necessary and at what interval.
The vaccine may induce a false-positive serologic test for Lyme disease. If Lyme disease is suspected in a vaccinated patient due to a positive ELISA assay, a Western blot test must be performed.2
Comments
LYMErix is the first vaccine marketed against Lyme disease. The vaccine stimulates the production of antibodies against the OspA. B. burgdorferi express OspA while in the midgut of the tick but is no longer detectable once the spirochete is injected into the human host. The vaccine-induced human antibodies must be taken up by the tick during its blood meal and interact with the B. burgdorferi in the midgut of the tick to prevent transmission of the spirochete to the human host.
The efficacy of the vaccine was determined in a multicenter, double-blind, randomized, 20-month trial involving more than 10,000 subjects who lived in endemic areas in the United States.4 Study sites were in Connecticut, Maine, Massachusetts, Rhode Island, Delaware, Maryland, New Jersey, New York, Pennsylvania, and Wisconsin. Since the vaccine does not prevent all cases of Lyme disease, individuals at risk of exposure must be encouraged to take standard preventive measures such has wearing long-sleeved shirts, pants, treating clothing with tick repellent, and checking for and removing ticks. In addition, the vaccine does not prevent other tick-borne infections such as babesiosis or ehrlichosis. LYMErix costs approximately $50 per injection or about $150 per course.
Clinical Implications
Lyme disease is a multisystem inflammatory disease. It usually, but not always, begins with erythema migrans (including the "bull’s-eye rash) and may be accompanied by flu-like symptoms. Weeks later, characteristics of early dissemination includes secondary skin lesions, neurologic involvement (e.g., meningitis, facial palsy), cardiac involvement (e.g., atrioventricular block), or migratory musculoskeletal pain may develop. Late dissemination includes episodes of arthritis and neurologic or psychiatric symptoms.1,6,7 The disease is frequently misdiagnosed, overdiagnosed, and overtreated, but it is also under reported and is a public health concern in endemic area.8,9 Lyme disease prevention, detection, and treatment are associated with substantial health care resources, and the disease can result in long-term morbidity.6,8,10
In the Northeast and Midwest the main vector is the deer tick (Ixodes scapularis) while in the west the vector is the western black-legged tick (Ixodes pacificus). Most cases result from bites by the nymphs which most commonly occur in late spring-summer, although infection is possible at any time of the year. The high-risk season may vary annually according to local weather conditions. The incidence varies from state to state but most cases are reported in the Northeast and upper Midwest. The highest reported case rates (per 100,000 population) in 1996 occurred in Connecticut (94.8), Rhode Island (53.9), New York (29.2), Pennsylvania (23.3), Delaware (23.9), and New Jersey (27.4). Moderate incidences of infection are reported by states such as Oklahoma, Kansas, Missouri, and Oregon (0.52-1.40 cases per 100,000) and the case rate in California in 1996 was only 0.3 cases per 100,000.1,2 The vaccine offers another strategy to prevent Lyme disease along with personal protection, insecticides, and wildlife management. Individuals most likely to benefit from vaccination are those who live, work, or spend their leisure time in endemic areas with frequent and prolonged exposure to wooded or grassy areas infested with Ixodes ticks. Widespread and routine use of the vaccine is not indicated. (Dr. Elliott is Chair, Pharmacy Education, California Division of Kaiser Permanente and Assistant Clinical Professor of Medicine, University of California San Francisco; Dr. Chan is Pharmacy Quality and Outcomes Manager, Kaiser Permanente, Oakland, CA.)
References
1. CDC. MMWR Morb Mortal Wkly Rep 1997;46:531-533.
2. LYMErix Product Information. SmithKline Beecham. December 1998.
3. Nowakowski J, et al. Ann Intern Med 1997;127: 130-132.
4. Steere AC, et al. N Engl J Med 1998;339:209-215.
5. Parenti DL, et al. IDSA 36th Annual Meeting. Abstract 705.
6. Shadick NA, et al. Ann Intern Med 1994;121:560-567.
7. Fallon BA, et al. Am J Psychiatry 1994;151:1571-1583.
8. Reid MC, et al. Ann Intern Med 1998;128:354-562.
9. Coyle BS, et al. J Infect Dis 1996;173:1260-1262.
10. Maes E. Clin Ther 1998;20:993-1008.
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