Question

• Is the recently approved live, trivalent, intranasal influenza vaccine (i.e.; Flumist®) effective in preventing influenza incidence in otherwise healthy children?

Clinical Bottom Lines

1. Although safe and effective, the intranasal vaccine's widespread use and replacement of the traditional intramuscular vaccine is currently limited by its cost, strict storage guidelines, and FDA licensure excluding key influenza vaccination target populations (e.g., healthy children <5 y/o, and children with chronic disease). Consequently, its usage is currently dependent upon the patient's clinical situation and financial resources.
2. The live, trivalent, intranasal vaccine was 93% effective in preventing influenza infection compared to the baseline study population.
3. Among initially seronegative children, the intranasal vaccine produced a significant antibody response to influenza strains contained in the vaccine.
4. The intranasal vaccine is generally well tolerated and safe; only nasal congestion, decreased activity, and mild fevers were significantly associated with the first dosage.
   

Summary of Key Evidence

1. The trial was a prospective, multi-center, double-blind, placebo-controlled, randomized control trial.¹
2. 1602 healthy children, ages 15-71 months old (average age 43 m/o), were randomized in a 2:1 ratio to receive the live, intranasal influenza vaccine versus placebo. Exclusion criteria included egg allergy and respiratory, cardiovascular, and immuno-deficiency related chronic illnesses.
3. The placebo was clinically indistinguishable from the experimental vaccine, containing the same inactive ingredients as the vaccine.
4. After vaccination, both groups were actively monitored for clinical symptoms suggestive of influenza infection (e.g., fever, malaise, headaches, congestion, myalgias, etc.). If subjects demonstrated the aforementioned symptoms, an influenza culture was sent to determine influenza infection to the vaccine's viral strains versus other viral etiology as the cause.
5. Subjects were further monitored for the vaccine's tolerability, and antibody response via scheduled blood draws.
6. Among the 1070 subjects randomized to the vaccination arm, 14 had culture confirmed influenza (1%). Among the 532 control subjects, 95 experienced one or more influenza infections (>17%).
7. The vaccine's overall efficacy, also referred to a Relative Risk Reduction (RRR), was determined to be 93% (95% Confidence Interval=88-96%).
8. Accordingly, the vaccine's Absolute Risk Reduction (ARR) was 17%, and its Number Needed to Treat (NNT) was 6 patients.
   

Additional Comments

• Flumist's current cost is a significant limitation to its widespread utility; the intranasal vaccine costs an average of $42.00/dose (@UMHS=$56.00/dose), compared to the inactivated intramuscular vaccine, which costs $6.25/injection (@UMHS=$20.00/injection).
• Furthermore, the intranasal vaccine has strict storage guidelines; it must be frozen, and if thawed, must either be used immediately, or stored at a low temperature (2-8°C) for <24 hours.
• Although the study supports the vaccine's safety and effectiveness in healthy children <5 years old, Flumist's current FDA licensure does not approve of its use in this age group, excluding a key population prone to influenza's yearly morbidity and mortality.
• There is no published study to date that directly compares the live intranasal vaccine in terms of efficacy and superiority over the traditional, inactivated, intramuscular influenza vaccine.
• The study was partially funded by the vaccine's manufacturer, Aviron Corp.
  

Citation

1. Belshe RB, et.al. The efficacy of live attenuated, cold-adapted, trivalent intranasal influenzavirus vaccine in children. N Engl J Med 1998; 338(20): 1405-12.

CAT Author: William Frese, MD

CAT Appraisers: Alex Kemper, MD

Date appraised: November 19, 2003