A look at the new needle-free flu vaccine
From the October ACP Observer, copyright © 2003 by the American College of Physicians.
By Gina Rollins
As influenza season approaches, many in the medical community are wondering what the newest influenza vaccine—a needle-free way to protect patients from the flu—will bring in the coming months.
Because the new vaccine, FluMist, doesn't have to be injected, it is sure to be popular with patients who don't like shots. A $50 million promotional campaign aimed at consumers and physicians is also expected to generate considerable discussion in physicians' offices in the coming months.
Because the vaccine is administered intranasally, some are saying it's the biggest innovation in influenza vaccines in 50 years. But the vaccine is also unique because it targets healthy individuals who have a fairly low flu risk. Because most flu vaccination campaigns have not historically targeted healthy people, FluMist's huge marketing campaign could encourage a whole new group of patients to come to your office seeking a flu vaccination.
Infectious disease experts who have followed the vaccine's development, however, say that several factors may keep it out of the offices of many physicians.
While no serious adverse events have been identified from the vaccine, patients can experience side effects including mild, flu-like symptoms. It is also unclear whether the live vaccine can be transmitted to patients at high risk for flu complications, who should not receive the new vaccine.
In addition, many insurers have so far refused to cover FluMist, which costs many times more than injectable vaccines. Those factors may put a dent in the number of patients who want to pay for FluMist out of pocket—and limit the number of medical practices that will offer it to their patients this year.
Considerations for high-risk patients
The FDA approved FluMist, a live vaccine, in June for healthy patients between 5 and 49. FluMist is a live-attenuated influenza vaccine (LAIV) that is administered nasally. Like this year's injectable influenza vaccine, it contains the three influenza virus strains targeted by public health officials for the 2003-2004 season: two strains of influenza A, and one B virus.
MedImmune Vaccines Inc., which manufactures FluMist, has said it will produce 4 million to 5 million doses this year. (The vaccine is being marketed jointly by MedImmune and Wyeth Vaccines.)
While no research has directly compared FluMist to other injectable flu vaccines, infectious disease experts say the new vaccine is promising.
"A mucosal immunization virus could theoretically induce a broader immune response because it enters through the respiratory tract," said Kathleen M. Neuzil, FACP, member of the ACP Adult Immunization Initiative advisory board and the College's representative to the CDC Advisory Committee on Immunization Practices. She added that without head to head comparisons of the two vaccines, however, it is not known if enhanced mucosal immunity will translate into improved clinical effectiveness.
Research has yielded some comparisons between FluMist and the injectable vaccine. In a small challenge study of healthy adults, the vaccine was 85% effective at preventing experimental influenza when compared to placebo. In children, a large randomized controlled trial found the vaccine was 87% effective against culture-confirmed influenza when compared to placebo.
For now, however, there are no comparable data for high-risk groups, including patients 65 and older, children under 5, and individuals with chronic medical conditions like pulmonary or cardiovascular diseases, diabetes, kidney disorders or immunosuppression from either medications or HIV. As a result, infectious disease specialists say FluMist should be given only to healthy individuals.
"The vaccine hasn't been shown to work in high-risk groups, so our advice is to remain within the labeling," said John J. Treanor, MD, associate professor of medicine at New York's University of Rochester and a researcher involved in FluMist clinical trials.
FluMist has also not been studied extensively in adults older than age 49, and its safety hasn't been established in patients with asthma or reactive airway disease, pregnant women or nursing mothers. There are also no safety data on FluMist in patients who are using other intranasal preparations like steroids and other vaccines.
And like the injectable flu vaccine, FluMist is not recommended for people who are allergic to eggs. It also shouldn't be given to patients with a history of Guillain-Barre syndrome or children 17 and younger who are taking aspirin or aspirin-containing medications.
Along with a lack of data on some patient groups, FluMist presents other potential clinical, financial and logistical disadvantages that could affect physicians' decision to offer the new vaccine. Here are some factors to keep in mind:
Side effects. Along with the three inactivated flu viruses that are featured in this year's injectable vaccines, FluMist also contains a genetic reassortant of a live master donor virus. The new vaccine is designed to produce an attenuated response.
"It's a live vaccine, but it's been mutated to have a restricted ability to grow in the respiratory tract," Dr. Treanor explained. "It grows enough to provoke an immune response, but not enough to produce the flu."
Clinical studies, however, have shown that compared to placebo, adult FluMist vaccinees experienced significantly more problems involving cough, running nose, sore throat, chills and tiredness or weakness. FluMist recipients also reported more episodes of nasal congestion, rhinitis and sinusitis.
For some physicians, those effects may raise concerns. "The potential for illness is mild," said Robert H. Hopkins Jr., FACP, associate professor of medicine and pediatrics at the University of Arkansas in Little Rock and a member of the College's Adult Immunization Initiative advisory board. "But I still worry that it might interfere with the message that patients can't get the flu from flu vaccine."
Dr. Neuzil said that educating patients about the symptoms they can expect from both the injected vaccine and FluMist may help clarify any misunderstandings about side effects. "We know the main side effect from the influenza shot is arm soreness near the injection site," she explained. With FluMist, on the other hand, "you could have an irritated nose or sore throat.
"These upper respiratory side effects, while mild, are more similar to some flu symptoms, and may be caused by limited viral replication." However, among healthy patients, FluMist hasn't been associated with systemic flu-like illness, she added, and no serious adverse events have been identified.
Transmission. Another concern is the possibility that FluMist recipients may transmit the virus after vaccination. While this issue has not been well-studied in adults, a study of children in a day care setting found the estimated probability of virus transmission to be 2.4%.
"Theoretically, the levels of virus shed by adults is less than the amount required to infect an adult," Dr. Treanor pointed out. "However, no one has designed a study to test that."
Because of the small but real potential for virus transmission, Dr. Hopkins suggested that all family members receive the new vaccine at the same time. "If you hit everybody at once," he said, "you'll avoid the problem of spreading infection one person at a time."
(For more on patients who should not receive FluMist, see "Which patients should not receive FluMist?")
Practices that plan to offer FluMist might want to set up a system to identify and immunize appropriate patients. One strategy is to designate an immunization champion in the office who is familiar with indications for both FluMist and injected flu vaccine. That person can talk to patients about which type of immunization is best for them.
Another strategy: Develop a self-screening tool that can be administered when patients check in for their visit. "You could use a simple form that asks whether or not the person wants a flu vaccine and then if they do or don't mind having an injection," Dr. Hopkins advised. "People who don't like needles could then answer some more questions about their own history and their households."
Cost and reimbursement. FluMist will cost $46 per dose and will be available in 20- and 50-dose lots. (A MedImmune spokesperson said the company will allow returns of up to 20 units.) By contrast, physicians can expect to pay an average of $8.50 per dose this year for injectable vaccine.
Patients who want FluMist instead of an injection will likely have to pay for it themselves, because insurance coverage for the vaccine right now appears to be limited. Aetna, which insures about 13 million people nationwide, has indicated that it will not cover FluMist because the new vaccine has not yet been proven to be more effective in preventing the flu than the injectable vaccine. Aetna also doesn't consider FluMist to be medically necessary for healthy people between the ages of 5 and 49.
Likewise, Tufts Health Plan in Boston is not covering FluMist. Officials say that the injectable vaccine reaches a broader population and is more cost-effective.
According to Dr. Hopkins, one health plan did tell him that it will probably cover FluMist, but only at the level that it reimburses for the injectable vaccine—about $20 for both shot administration and the vaccine. That is less than half what physicians will pay for the vaccine.
A MedImmune spokesperson said that because the company is still negotiating with payers, more health plans may ultimately cover the new vaccine. MedImmune is also in discussions with pharmacies about offering the vaccine, so physicians who don't plan to stock it may be able to refer patients to their local pharmacy to be immunized.
And even without insurance coverage, patient demand for FluMist may still be strong. "Individual patients may be willing to pay for the vaccine out of pocket if the reason they're taking it is to avoid an injection," Dr. Neuzil said.
Storage requirements. Because the FluMist vaccine is cold-adapted and temperature sensitive, it must be stored at or below -15 C (5 F) in a freezer that is not "frost-free." (Frost-free freezers do not maintain a constant temperature.) The vaccine can be thawed in a refrigerator and stored at 2-8 C (36-46 F) for no more than 24 hours.
According to Dr. Neuzil, these temperature requirements could cause problems for average internal medicine practices that don't see children or stock varicella vaccine, which has similar storage requirements.
MedImmune is offering a special storage container that will allow practices to store FluMist in the freezer compartments of frost-free refrigerators. But the container's dimensions (14-5/8 inches long by 9-1/2 inches wide by 8-1/16 inches high) mean it will likely not fit in the freezer compartments of mini-refrigerators used by many practices.
A MedImmune spokesperson said that the container should fit horizontally in the freezer section of a standard-size household refrigerator. (Practices interested in a free freezer storage box should call 800-358-7443 or contact their Wyeth vaccine representative.)
Wal-Mart has announced that it will offer FluMist at its pharmacies beginning Oct. 1, at "the best available price," a Wal-Mart spokesperson said. In states where pharmacists can administer vaccines according to a physician-approved protocol, healthy adults ages 18 to 49 will not need a prescription to get FluMist at Wal-Mart. (Adolescents 12-17 and adults over 50 will need to present a prescription.)
But given the cost and logistical barriers, as well as the lack of data for high-risk populations, many practices may decide to pass on FluMist this season.
"Although it's a promising innovation, the cost is high relative to the usual form of vaccination," said Allan H. Goroll, FACP, a general internist at Boston's Massachusetts General Hospital and a member of the ACP Adult Immunization Initiative advisory board. "The absence of extensive safety and efficacy data, especially data from everyday practice, is also likely to limit initial adoption."
It's not clear how many physicians will actually offer FluMist this year. Dr. Hopkins, for example, said he intends to survey his patients over the next several months and, depending on their interest, he may offer it next year.
Whether or not you plan to offer FluMist, you should expect to spend time discussing it with patients. "We'll get a lot of questions from the public," said Dr. Neuzil, "so we need to be educated."
Gina Rollins is a freelance writer in Silver Spring, Md.
The information included herein should never be used as a substitute for clinical judgment and does not represent an official position of ACP.
Which of your patients should not receive the FluMist vaccine? Kathleen M. Neuzil, FACP, member of the ACP Adult Immunization Initiative advisory board and the College's representative to the CDC Advisory Committee on Immunization Practices, identified the following individuals:
- Patients with egg allergy. Because FluMist is grown in eggs, persons with egg allergy should not receive the vaccine.
- Immunocompromised individuals. Because FluMist is a live virus that is capable of replication, immunocompromised persons should not receive FluMist.
- Patients at high risk for complications of influenza infection. Until researchers have more data, populations at high risk for developing complications from influenza infection (patients with asthma, cystic fibrosis, chronic obstructive pulmonary disease, and people 65 and older) should not be vaccinated with a live-attenuated influenza vaccine.
- Pregnant women.
The recommended dosage of FluMist for children and adults age 9 and older is 0.5 mL per season, delivered via a pre-filled single-use sprayer. Children between the ages of 5 and 8 who haven't received FluMist in the past should have two 0.5 mL doses administered at least six weeks apart. In subsequent seasons, children in this age group need only one 0.5 mL dose.
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