Document text
Safety of Live Attenuated
Influenza Vaccine in
Children with Asthma
C. Buddy Creech, MD, MPH
Edie Carell Johnson Chair and Professor, Pediatric Infectious Diseases
Director, Vanderbilt Vaccine Research Program
Vanderbilt University Medical Center
Nashville, Tennessee
Advisory Committee on Immunization Practices (ACIP) Meeting
February 28, 2024
Disclaimer
•The findings and conclusions in this presentation are those of the presenter and
do not necessarily represent the official position of the Centers for Disease Control and Prevention
•Mention of a product or company name is for identification purposes only and does not constitute endorsement by CDC
•This study was supported by the CDC Clinical Immunization Safety Assessment (CISA) Project
•Dr. Creech reports the receipt of consulting fees from Pfizer, Moderna, Sanofi, GSK, TD Cowen Investments, and CommenseBio ; grant support from Moderna;
and royalties from UpToDate. None are related specifically to influenza vaccines or asthma
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Duke University
Amy Stallings, MD
Chris Todd, MPH
Sue Doyle, LPN
Lynn Harrington, RN, BSNLori Hendrickson, RN, BSNBeth Patterson, RN, BSN
Luis Ballon
Joyce Gandee
Erica SuarezCincinnati Children’s Hospital
Mary Allen Staat , MD, MPH
Carolyn Kercsmar , MD
Marilyn Rice, MSValerie Sackenheim , RN, CPN
Joe Sorter, BAJeanne Kleiman, BS, ALC, CCRPVanderbilt University Medical Center
C. Buddy Creech, MD, MPHAndrew Sokolow, MD
Kathryn Edwards, MD
Natalia Jimenez, PhD, MSCIShanda Phillips, RN, BSNKate Sokolow, RN, MSN
Braxton Hern, BS
Paula Campbell, MPHYuwei Zhu, MDCDC
Karen Broder, MDTheresa Harrington, MD, MPHTM (retired)
Frank DeStefano, MD, MPH (retired)
Lisa Grohskopf , MD, MPH
Oidda Museru , RN, MPH
Suzanne Beavers, MD A. Patricia Wodi, MD
Bottom Line, Up Front
In a study of 142 children
with persistent asthma,
LAIV4 was not associated with
increased frequency of asthma
exacerbations, increase in asthma -
related symptoms, or decrease in
peak expiratory flow rate (PEFR)
in the 6 weeks following vaccination
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Ann Allergy Asthma
Immunol 2017
Vaccines 2017
In these studies, children with asthma who received LAIV were not found
to have a higher incidence of lower respiratory events
JACI 2020
6Study Population:
5 – 17-year -old
children with
persistent asthma
Primary Objective and Definitions
To compare the proportion of participants experiencing an asthma
exacerbation during the 42 days after LAIV4 vs. IIV4
•Scientific Hypothesis: LAIV4 is non-inferior to IIV4
•Null Hypothesis: Expressed statistically, the hypothesis was that the proportion of
children experiencing an asthma exacerbation in the LAIV4 group would be ≥10% higher than the proportion in the IIV4 group.
Persistent Asthma: Provider diagnosis of asthma + prescription of a long -
acting controller medication
•Note: This is distinct from intermittent asthma , in which children may have
intermittent, mild symptoms or require infrequent doses of albuterol
Asthma Exacerbation : An acute episode of progressively worsening
shortness of breath, cough, wheezing, chest tightness, or respiratory distress
for which the patient seeks medical attention or receives a new prescription for systemic corticosteroids.
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Relevant Exclusion Criteria
•Acute illness (with or without fever) within 72 hours of enrollment or use
of antipyretics within 24 hours led to a temporary delay in vaccination
•Recent receipt of inactivated vaccine (14 days) or live vaccine (28 days) or planned receipt of any vaccine within 42 days of vaccination
•Children with immunosuppression, including those who had received 20 mg of prednisone (or greater) for more than 14 days in the previous month, were excluded.
•Children who had a life- threatening exacerbation in the previous 2 years or
any exacerbation in the month prior to enrollment
•Use of influenza- specific antiviral medication within 48 hours of enrollment
•Currently receiving aspirin
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Additional Eligibility Issues
Post -menarchal females had urine or serum pregnancy testing prior to
enrollment
For children 5 -8 years of age who required two doses of vaccine based
upon ACIP recommendations, enrollment could occur after either the
first or the second dose of vaccine.
•If enrollment occurred after the first dose, the study staff instructed the
family to delay 2nd vaccination until after study follow- up was completed
unless widespread influenza disease activity was detected in the community.
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70% of participants were classified as having moderate or severe asthma
There were slightly more males than females (p=0.5)Black individuals comprised >30% of the study population; approximately 5% were Hispanic or Latino
In the 14 days following vaccination, we observed 3 exacerbations
among LAIV4 recipients and 4 in IIV4 recipients (3.9% vs. 5.7%, p=0.74)
In the 42 days following vaccination, we observed 8 exacerbations in
the LAIV4 group and 10 in the IIV4 group (10.8% vs. 14.7%, p=0.71)
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Given that the upper bound for non- inferiority was 10% (0.1), a difference in
proportion of - 3.9% (CI: 90% CI: - 0.15, 0.07) means that we can reject the null
hypothesis that LAIV4 is inferior to IIV4.
LAIV4 was not associated with increased asthma symptoms
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No significant differences were seen when
comparing across age groups (5 -11 years of
age, 12 -17 years of age), study site, or
asthma severity (mild/moderate vs. severe)
PEFR: Peak Expiratory Flow Rate
Myalgia and sore throat were more common in IIV4 recipients
Strengths and Limitations of the Study
Strengths
•Multicenter, prospective, randomized, and controlled
•Enriched for children with persistent asthma and those with moderate to severe asthma
•Captured asthma symptoms in addition to asthma exacerbations and medical utilization
•Captured reactogenicity data
•Enrolled over two influenza seasons, increasing generalizability
Limitations
•Enrolled fewer participants than originally intended, but posterior power calculations revealed
adequate power (79%) to detect differences between groups
•Enrolled over two influenza seasons, leading to slightly different products
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Summary and Conclusions
LAIV4 was not associated with increased asthma symptoms or
asthma exacerbations in the 14 - or 42 -days following immunization
Rates of reactogenicity were similar between IIV4 and LAIV4, though myalgia and sore throat were more common in the IIV4 arm
LAIV4 may be a suitable option for children ≥5 years with asthma, including moderate to severe asthma
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Duke University
Amy Stallings, MD
Chris Todd, MPH
Sue Doyle, LPN
Lynn Harrington, RN, BSNLori Hendrickson, RN, BSNBeth Patterson, RN, BSN
Luis Ballon
Joyce Gandee
Erica SuarezCincinnati Children’s Hospital
Mary Allen Staat , MD, MPH
Carolyn Kercsmar , MD
Marilyn Rice, MSValerie Sackenheim , RN, CPN
Joe Sorter, BAJeanne Kleiman, BS, ALC, CCRPVanderbilt University Medical Center
C. Buddy Creech, MD, MPHAndrew Sokolow, MD
Kathryn Edwards, MD
Natalia Jimenez, PhD, MSCIShanda Phillips, RN, BSNKate Sokolow, RN, MSN
Braxton Hern, BS
Paula Campbell, MPHYuwei Zhu, MDCDC
Karen Broder, MDTheresa Harrington, MD, MPHTM (retired)
Frank DeStefano, MD, MPH (retired)
Lisa Grohskopf , MD, MPH
Oidda Museru, RN, MPHSuzanne Beavers, MD A. Patricia Wodi, MD
Discussion
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