National Geographic : 1999 Mar
LYMErix" Lyme Disease Vaccine (RecombinantOspA) Brief Summary. Please see complete prescribing information in SmithKline Beecham Pharmaceuticals literature. INDICATION AND USAGE: LYMErix is indicated for active immunization against Lyme disease in individuals 15 to 70 years of age. Individuals most at risk may be those who live or work in Borrelia burgdorferi-infected tick infested grassy or wooded areas (e.g ., landscaping, brush clearing, forestry, and wildlife and parks management), as well as those who plan travel to or pursue recreational activities (e.g., hiking, camping, fishing and hunting) in such areas. Most cases of Lyme disease in the United States are thought to be acquired in the peri-residential environment, through routine activities of property maintenance, recreation, and/or exercise of pets. Previous infection with B. burgdorferi may not confer protective immunity. Therefore people with a prior history of Lyme disease may benefit from vac cination with LYMErix. Safety and efficacy for this vaccine are 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 (see DOSAGE AND ADMINISTRATION in complete prescribing information). LYMErix is not a treatment for Lyme disease. As with any vaccine, LYMErix may not protect 100% of individuals. Do not administer Lymerix to persons outside of the indicated age range. CONTRAINDICATIONS: Contraindicated in people with known hypersensi tivity to any component of LYMErix. PRECAUTIONS: General: LYMErix will not prevent disease in those who have unrecognized infection at the time of vaccination. LYMErix will not pro vide protection against other tick-borne diseases such as babesiosis or ehrlichiosis. Treatment-resistant Lyme arthritis (antibiotic refractory), a rare complication of B. burgdorferi infection, has been associated with immune reactivity to OspA of B. burgdorferi. Since the underlying etiology is not clearly understood, it is recommended that LYMErix not be administered to such patients. As with other vaccines, although a moderate or severe febrile illness is sufficient reason to postpone vaccination, minor illnesses such as mild upper respiratory infections with or without low-grade fever are not contraindications. Before the injection of any biological, the physician should take all reasonable precautions to prevent allergic or other adverse reac tions, including understanding the use of the product concerned, and the nature of the side effects and adverse reactions that may follow its use. Prior to immunization with any vaccine, the physician should review the patient's immunization history for possible vaccine sensitivity, previous vac cination-related adverse reactions and occurrence of any adverse-event related symptoms and/or signs, in order to determine the existence of any contraindication to immunization and to allow an assessment of benefits and risks. Epinephrine injection (1:1000) and other appropriate agents used for the control of immediate allergic reactions must be immediately available should an acute anaphylactic reaction occur. Packaging for the LYMErix Tip-LokTM syringe contains dry natural rubber, which may cause allergic reactions; packaging for the vial does not contain natural rubber. Use a separate sterile syringe and needle or a sterile disposable unit for each patient to prevent transmission of infectious agents from person to person. Dispose of needles properly and do not recap. As with any vaccine administered to immunosuppressed persons or persons receiving immuno suppressive therapy, the expected immune response may not be obtained. For individuals receiving immunosuppressive therapy, consider deferring vaccination for 3 months after therapy. Laboratory Test Interactions: LYMErix immunization results in the gener ation of anti-OspA antibodies, which can be detected by an enzyme-linked immunosorbent assay (ELISA) for B. burgdorferi. The incidence of positive IgG ELISA tests depends on the sensitivity and specificity of the ELISA assay and the titer of anti-OspA antibody. In general, there is an association between anti-OspA titer and IgG ELISA index or Optical Density (OD) ratio; the higher the titer of anti-OspA achieved, the higher the IgG ELISA index or OD ratio. Therefore, because vaccination may result in a positive IgG ELISA in the absence of infection, it is important to perform Western blot ttttesting if the ELISA test is positive or equivocal invaccinated individuals who are being evaluated for suspected Lyme disease. Following vaccina tion, the appearance of a 31kD OspA band, possibly accompanied by other lower molecular weight bands on an immunoblot (Western blot), should not interfere with the determination of positivity when assessed by CDC/ ASTPHLD criteria. Drug Interactions: No data are available on the immune response to LYMErix when administered concurrently with other vaccines. As with other intramus cular injections, do not give LYMErix to individuals on anticoagulant therapy, unless potential benefit clearly outweighs risk of administration. Carcinogenesis, Mutagenesis, Impairment of Fertility: LYMErix has not been evaluated for carcinogenic or mutagenic potential, or for impairment of fertility. Pregnancy: Teratogenic Effects: Pregnancy Category C. Animal repro ductive studies have not been conducted with LYMErix. It is also not known whether LYMErix can cause fetal harm when administered to a pregnant woman or can affect reproductive capacity. Give LYMErix to a pregnant woman only if clearly needed. Health care providers are encouraged to reg ister pregnant women who receive LYMErix [Lyme Disease Vaccine (Recombinant OspA)] in the SmithKline Beecham Pharmaceuticals vaccina tion pregnancy registry by calling 1-800-366-8900, ext. 5231. Nursing Mothers: It is not known whether LYMErix is excreted in human milk. Because many drugs are excreted in human milk, use caution when LYMErix is administered to a nursing woman. Pediatric Use: Safety and efficacy in pediatric subjects younger than 15 years of age have not been evaluated. Therefore, the vaccine is not indi cated for this age group at this time. ADVERSE REACTIONS: During clinical trials involving 6,478 individuals re ceiving a total of 18,047 doses, LYMErix has been generally well tolerated. Subjects with the following conditions: chronic joint or neurologic illness related to Lyme disease; diseases associated with joint swelling (including rheumatoid arthritis) or diffuse musculoskeletal pain; second- or third degree atrioventricular block or a pacemaker were excluded from the efficacy trial because such conditions could interfere with the assessment of Lyme disease in the trial. Therefore, data are limited regarding the safety of the vaccine in subjects with these conditions (see below). Unsolicited Adverse Events: The most frequently reported (>1%) unsolicited adverse events within 30 days of vaccination for all subjects receiving at least one dose (n=10,936) in the double-blind, placebo-controlled efficacy trial are shown in Table 1. Table1.Incidence (>1%)ofUnsolicited AdverseEventsOccurring Within 30 Days Following EachDose*andOverall(after Doses1,2 or3) Dose 1 2 3 Overall VaccinePlaceboVaccinePlaceboVaccinePlaceboVaccinePlacebo (N=546)(N=567) (N=5397)(N5417) (N500 (N(0N=5018) (N=5469)(N=5467 Events % % % % % % % % Local Injectionsitepain 1796' 490 8.76 295 21.87 691 Injectionsite reaction 154 b 091 General BodyasaWhole Achiness 157 1.19 1.22 0.90 2.78 2.25 Chills/Rigors 2 05' 0.73 Fatigue 203 1.96 1.72 142 3.86 342 Fever 1.35' 0.91 2.58' 1.61 Infectionviral 188 1.66 2.83 245 Influenza-like symptoms 1.44' 093 2.54' 166 Nausea _ 1.12 104 Musculoskeletal System Arthralgia 322 2.67 3.11 260 1.24 1.16 6.78 6.05 Backpain 190 1.55 Myalgia 269' 172 1.52' 0.98 4.83' 294 Stiffness ___ 095 1.21 Nervous System Dizziness 101 1.08 Headache 3.51 2.96 2.39 233 5.61 509 Respiratory System Bronchitis 1.10 1.28 Coughing 150 146 Pharyngitis 139 112 115 1.20 2.52 245 Rhinitis 150 1.46 2.41 247 Sinusitis 174 157 1.26 127 3.16 2.93 Upperrespiratory tractinfection 263 3.22 165 1.75 _4.35 4.98 Skin/Appendage3 Rash 137 108 SIncludeseventsobtainedthroughspontaneous reportsfollowingeachdoseandeventsreported 1monthafter doses1and2 (whenall subjectswerequeriedregardingtheoccurrenceofanyadverseeventsincetheprevi ousvaccination). a. p-value<005 b. p-value<001. c p-value<0.001 The most frequently reported (>1%) unsolicited adverse events occurring more than 30 days (late) after vaccination for all subjects (n=10,936) were similar in nature to those listed in Table 1, and most occurred at a frequency of <5%, in both the vaccine or placebo groups. The only late adverse events occurring with an incidence of >5% in vaccine or placebo recipients were arthralgia (13.64% vs. 13.55%, respectively) and headache (5.06% vs. 4.72%, respectively). No significant differences in late adverse events were noted between treatment groups after any dose and overall. Separate post hoc analyses were conducted to assess two subsets of mus culoskeletal events which occurred either early (530 days) or late (>30 days) post-vaccination. There were no significant differences, either early or late, between the vaccine and placebo recipients with regard to experiencing arthritis, aggravated arthritis, arthropathy or arthrosis. However, vaccine recipients were significantly more likely than placebo recipients to experi ence early events of arthralgia or myalgia after each dose [for dose 1: odds ratio (OR), (95% CI) = 1.35 1.13, 1.61); dose 2: OR = 1.28 (1.05, 1.56); dose 3: OR = 1.59 (1.18, 2.16)]. With regard to late events of arthralgia or myal gia, there were no significant differences between vaccine and placebo recipients. There was no significant difference in the rates of cardiac adverse events between vaccine and placebo recipients. Neurologic adverse events which occurred at a rate <1% in the vaccine group and were noted to occur with a similar frequency in placebo recipients included: carpal tunnel syndrome, migraine, paralysis, tremor, coma, dysphonia, ataxia, multiple sclerosis, myasthenia gravis, meningitis, trigeminal neuralgia, nystagmus, neuritis, neuralgia, nerve root lesion, neuropathy, hyperesthesia, hyperkinesia, and intracranial hypertension. Overall, approximately 18% of subjects enrolled in the study had a prior his tory of some musculoskeletal condition (19% vaccinees, 18% placebo recip ients). In a post hoc subgroup analysis, there was no significant difference between vae anlaccine and placebo recipients with regard to development of musculoskeletal events (defined as arthritis, arthropathy, arthrosis, synovi tis, tendinitis, polymyalgia rheumatica, bursitis or rheumatoid arthritis and lasting more than 30 days) in those with a prior history of musculoskeletal conditions. However, both vaccine and placebo recipients with a prior history of musculoskeletal conditions were more likely to experience muscu loskeletal events than subjects without such prior history. Solicited Adverse Events: The frequency of solicited local and systemic adverse events was evaluated in a subset of subjects (n=938) who com prised the total enrollment at one study center in the efficacy trial. Of these 938 subjects, 800 completed a 4-day diary card following each of three doses, and were evaluable according to protocol. Table 2 shows the per centage of subjects reporting a solicited symptom following any one of the three doses and overall. The majority of the solicited events were mild to moderate in severity and limited in duration.