Document text
Monitoring the Safety of Nirsevimab
in Infants Birth through <8 Months
June 25, 2025Matthew F. Daley, MDPreliminary Results from the Vaccine
Safety Datalink for the 2024 -2025 Season
KAISER PERMANENTE INSTITUTE FOR HEALTH RESEARCH
•No conflicts of interest
•Presenting on behalf of the Vaccine Safety Datalink (VSD) teamDisclosures and Acknowledgments
Nirsevimab Safety Surveillance Slide 2
Background
Slide 3
KAISER PERMANENTE INSTITUTE FOR HEALTH RESEARCH
•Long -acting monoclonal antibody, licensed for prevention of lower
respiratory tract disease in infants caused by RSV
•Recommendations for use:
oAll infants aged birth through <8 months (if no RSV vaccine during pregnancy)
oHigh-risk infants aged 8 -19 months
•High efficacy in phase 3 trial, high effectiveness post -licensure
•Severe shortage during 2023 -2024 season
•RSV prevention ( nirsevimab or vaccine): 72% uptake in VSDNirsevimab Overview
Nirsevimab Safety SurveillanceRef: 1) Muller WJ et al, N Engl J Med 2023;388(16):1533 -1534; 2) Jones JM et al, MMWR 2023;72(34):920 -925.
3) Moline HL et al, JAMA Pediatr 2025;179(2):179 -187. 4) Irving SA et al, Pediatrics 2025;155(6):e2024070240.
Slide 4
KAISER PERMANENTE INSTITUTE FOR HEALTH RESEARCH
•Across 3 randomized trials: n=3,184 received nirsevimab , n=1,284
received placebo, n=304 received palivizumab
•Adverse events generally balanced among infants who received
nirsevimab versus comparator
•Adverse events of special interest included 7 nirsevimab -exposed
infants with rashes, primarily papular or maculopapular
•No anaphylaxis, no serious hypersensitivity -type reactions reported
•No immune complex diseases reportedNirsevimab Safety, Clinical Trials
Nirsevimab Safety SurveillanceRef: 1) Muller WJ et al, N Engl J Med 2023;388(16):1533 -1534. 2) Mankad VS et al, Pathogens 2024;13(6):503.
Slide 5
KAISER PERMANENTE INSTITUTE FOR HEALTH RESEARCH
•Additional post -licensure safety data needed, including assessment
of rare adverse events, and when nirsevimab given during routine
care in a general patient population
•Objective: To investigate the safety of nirsevimab , by examining pre -
specified adverse events among nirsevimab recipients in the Vaccine
Safety Datalink (VSD)
•Nirsevimab is a passive immunization; CDC and ACIP requested that
VSD evaluate its safetyPost -Licensure Safety of Nirsevimab
Nirsevimab Safety Surveillance Slide 6
KAISER PERMANENTE INSTITUTE FOR HEALTH RESEARCH
•Collaboration between CDC and 13 healthcare organizations
•Observational; uses electronic health record (EHR) data
•Has ~15.5 million individuals overall; annual birth cohort ~115,000
•Data characteristics:
oElectronic health records, claims, immunization information systems
oDiagnoses, vaccines, medications ordered
oInpatient, emergency departments, outpatient
•VSD applies a range of analytic methods to address confounding,
including self -controlled designsVaccine Safety Datalink (VSD)
Nirsevimab Safety SurveillanceRef: 1) McNeil MM et al, Vaccine. 2014 Sep 22;32(42):5390 -8.
Slide 7
KAISER PERMANENTE INSTITUTE FOR HEALTH RESEARCH
VSD in 2025
Nirsevimab Safety Surveillance
Slide 8
KAISER PERMANENTE INSTITUTE FOR HEALTH RESEARCH
•Received nirsevimab , n=36,719
•Adverse events monitored, self -controlled risk interval (SCRI):
oAll analyses stratified by age group (neonates; infants)
oSeizures, ITP, drug reaction, fever or sepsis (neonate cohort only)
oNone showed elevated risk
•Exposure -dependent events: monitored case counts
oAnaphylaxis: no cases detected
oNon-anaphylactic allergic reactions: urticaria, often same day as nirsevimabSafety Results, VSD, 2023 -2024 Season
Nirsevimab Safety Surveillance Slide 9
Methods
Slide 10
KAISER PERMANENTE INSTITUTE FOR HEALTH RESEARCH
•Setting: all VSD data -contributing sites
•Population: all infants 0 days through <8 months of life who received
nirsevimab between October 1, 2024, and February 1, 2025
•Same -day vaccines: study included all nirsevimab -exposed infants,
regardless of whether they received vaccines same day as nirsevimab
•Health insurance enrollment: through control window
•Study design: primarily used SCRI
•Excluded infants born to someone who received RSV vaccine during
pregnancyMethods Overview
Nirsevimab Safety Surveillance Slide 11
KAISER PERMANENTE INSTITUTE FOR HEALTH RESEARCH
•Self-controlled risk interval is a form of self -controlled case series study
•Commonly used design in vaccine safety studies
•Rationale: exposed (to vaccine, or to nirsevimab ) often differ in important
characteristics from unexposed; these characteristics typically not
measured in electronic health record (EHR) data and can confound safety
assessments
•These are within -individual designs; control for measured and unmeasured
confounders that do not vary over time; example, a prevalent chronic
conditionSelf-Controlled Designs in Safety Studies
Nirsevimab Safety Surveillance Slide 12Ref: 1) Nie X et al, Expert RevVaccines 2022;21(3):313 -324. 2) Weldeselassie YG et al, Epidemiol Infect 2011;139(12):1805 -
17. 3) Li R et al, J Biopharm Stat 2016;26(4):686 -93. 4) Bots SH et al, Am J Epidemiol. 2025;194(1):208 -219.
KAISER PERMANENTE INSTITUTE FOR HEALTH RESEARCH
•Diagnoses in first month of life often related to pregnancy, delivery,
newborn -specific conditions
•Health care utilization different in first month of life
•Lags in health insurance enrollment
•With the exception of birth dose of hepatitis B vaccine, earliest all
other vaccines recommended: 38 days of age
•Separate safety analyses:
oNewborns: defined as 0 days through 37 days of age
oInfants (out of newborn period): 38 days through <8 months of ageAge Effects
Nirsevimab Safety Surveillance Slide 13
KAISER PERMANENTE INSTITUTE FOR HEALTH RESEARCH
•Rationale for pre -specified adverse events:
oBiologic plausibility
oClinical trial data
oExpert opinion
oFeedback from ACIP RSV Work Group
•Identified based on ICD -10 diagnosis codes, laboratory data
(platelet counts)Adverse Events Monitored
Nirsevimab Safety Surveillance Slide 14
KAISER PERMANENTE INSTITUTE FOR HEALTH RESEARCH
Outcomes for Nirsevimab Safety Surveillance Study
Nirsevimab Safety SurveillanceAdverse event Design
Seizures Self-controlled risk interval
Immune thrombocytopenia (ITP) Self-controlled risk interval
Drug reaction Self-controlled risk interval
Fever or sepsis (neonates only) Self-controlled risk interval
Anaphylaxis Counts monitored
Non-anaphylactic serious allergic reaction Counts monitored
Autoimmune, immune complex disease Outcomes rare, may have long latency; examine as
case -control at end of surveillance
Slide 15
KAISER PERMANENTE INSTITUTE FOR HEALTH RESEARCH
Self-Controlled: Risk and Control Windows
Nirsevimab Safety SurveillanceAdverse eventAge at nirsevimab
administrationRisk
window
(days)Control
window
(days) Setting
Seizure 0-37 days 0-7 8-21 Inpatient, ED
38 days to <8 months 0-7 8-21 Inpatient, ED
Immune thrombocytopenia 0-37 days 1-21 22-42 Inpatient, ED, outpatient
38 days to <8 months 1-21 22-42 Inpatient, ED, outpatient
Drug reaction 0-37 days 0-7 8-15 Inpatient, ED
38 days to <8 months 0-7 8-15 Inpatient, ED
Fever or sepsis (neonates
only)0-37 days 0-7 8-15 Inpatient, ED
Slide 16
KAISER PERMANENTE INSTITUTE FOR HEALTH RESEARCH
Exposure -Dependent Events: Case Counts Monitored
Nirsevimab Safety SurveillanceAdverse eventAge at nirsevimab
administrationRisk
window
(days) Setting Manual review
Anaphylaxis 0-37 days 0-2 Inpatient,
EDAll cases will be manually
reviewed
38 days to <8 months 0-2 Inpatient,
EDAll cases will be manually
reviewed
Non-anaphylactic allergic
reactions0-37 days 0-7 Inpatient,
EDCases reviewed if
indicated
38 days to <8 months 0-7 Inpatient,
EDCases reviewed if
indicated
Slide 17
KAISER PERMANENTE INSTITUTE FOR HEALTH RESEARCH
Outcomes for Nirsevimab Safety Surveillance Study
Nirsevimab Safety SurveillanceAdverse event ICD-10 codes Additional information
Seizure G40, R56, P90 First episode in 30 days
Immune
thrombocytopeniaD69.3, D69.6, P61.0 Also required platelets <50,000; first episode in
90 days
Drug reaction P93, T80.22, T80.29,
T80.8, T80.9Example: “Infection following…therapeutic
injection”; first episode in 30 days
Fever or sepsis
(neonates only)P36.9, R50.82, R50.83,
R50.9, T81.1, T81.4First episode in 30 days
Anaphylaxis T80.5, T78.2, T88.6, P81.1 First episode in 30 days
Non-anaphylactic serious
allergic reactionT80.6, T78.3, L50.0,
L50.1, L50.9, P83.88First episode in 30 days
Slide 18
KAISER PERMANENTE INSTITUTE FOR HEALTH RESEARCH
•For each pre -specified outcome:
oIdentify cases that occur within either risk or control window
oTwo observations per individual: One per control window and risk
window
oInformative cases have outcome in one window but not the other
oCohort must have at least one outcome in each window to estimate
effect
•Models stratified by age group
•Fixed -effects Poisson regression
oIndividual: Within person comparison across windows controls for
measured and unmeasured time -invariant factorsAnalytic Methods: SCRI Analysis
Nirsevimab Safety Surveillance Slide 19
Results
Slide 20
KAISER PERMANENTE INSTITUTE FOR HEALTH RESEARCH
Children 0 days old to < 8 months old 01OCT24 -01FEB25
(n=117,427)
Enrolled from at least 38 days old and at least 1 day between 01OCT24 -01FEB25
(n=92,418, 79%)
Nirsevimab
(n=43,532, 47%)
No RSV vaccine during pregnancy
(n=41,869, 96%)
38 days to < 8 months at index
(n=28,208, 67%)
Administered prior to season
(n=154, <1%)Administered this season
(n=28,054, 99%)0-37 days old at index
(n=13,661, 33%)
Administered this season
(n=9,855, 81%)Administered prior to season
(n=3,806, 19%)RSV vaccine during pregnancy
(n=1,663, 4%)No nirsevimab
(n=48,886, 53%)
Nirsevimab Safety SurveillanceStudy Flow
Slide 21
KAISER PERMANENTE INSTITUTE FOR HEALTH RESEARCH
Doses by
Week of Age
Nirsevimab Safety SurveillanceNote :
0 week=aged 0 -6 days
1 week=aged 7 -13 days
And so forth
Slide 22
KAISER PERMANENTE INSTITUTE FOR HEALTH RESEARCH
Neonate
Cohort:
Doses by
Days of Age
Nirsevimab Safety Surveillance Slide 23
KAISER PERMANENTE INSTITUTE FOR HEALTH RESEARCH
•Among neonates (0 -37 days old) who received nirsevimab :
oN=2,954 (20%): received on same day as hepatitis B vaccine
•Among infants 38 days through <8 months who received nirsevimab :
oN=24,847 (84%): received on same day as vaccines
oMost common combination: nirsevimab plus hepatitis B, rotavirus, DTaP, Hib,
pneumococcal, and polio vaccines (n=15,252)Simultaneous (Same -Day) Receipt of Vaccines
Nirsevimab Safety Surveillance Slide 24
KAISER PERMANENTE INSTITUTE FOR HEALTH RESEARCH
Self-controlled Risk Interval Results: Seizures
Nirsevimab Safety SurveillanceAdverse
eventAge
groupn Risk
window
(days)Control
window
(days)N cases
in risk
windowN cases
in
control
windowRR 95% CI P-value
Seizures 0-37
days9,855 0-7 8-21 4 2 3.50 0.64, 19.11 0.148
38 days
to <8
months28,054 0-7 8-21 5 2 4.38 0.85, 22.55 0.078
•2023 -2024 season: non -significant also; no elevated risk of seizures
Slide 25
KAISER PERMANENTE INSTITUTE FOR HEALTH RESEARCH
Self-controlled Risk Interval Results: ITP
Nirsevimab Safety SurveillanceAdverse
eventAge
groupn Risk
window
(days)Control
window
(days)N cases
in risk
windowN cases
in
control
windowRR 95% CI P-value
ITP 0-37
days9,817 1-21 22-42 0 0 N/A N/A N/A
38 days
to <8
months28,023 1-21 22-42 1 0 N/A N/A N/A
•Case definition required a diagnosis, and a platelet count below 50,000, within
21 days of each other, taking first of 2 dates
Slide 26
KAISER PERMANENTE INSTITUTE FOR HEALTH RESEARCH
Self-controlled Risk Interval Results: Drug Reaction
Nirsevimab Safety SurveillanceAdverse
eventAge
groupn Risk
window
(days)Control
window
(days)N cases
in risk
windowN cases
in
control
windowRR 95% CI P-value
Drug
reaction0-37
days9,855 0-7 8-15 0 0 N/A N/A N/A
38 days
to <8
months28,054 0-7 8-15 0 0 N/A N/A N/A
Slide 27
KAISER PERMANENTE INSTITUTE FOR HEALTH RESEARCH
Self-controlled Risk Interval Results: Sepsis and Fever
Nirsevimab Safety SurveillanceAdverse
eventAge
groupn Risk
window
(days)Control
window
(days)N cases
in risk
windowN cases
in
control
windowRR 95% CI P-value
Sepsis
and fever0-37
days9,855 0-7 8-15 4 9 0.44 0.14, 1.44 0.18
•Only for newborn cohort (not conducted for 38 days to <8 months of age)
•Additional exploratory analysis performed to assess whether nirsevimab could
cause fever, leading to sepsis workup (blood, CSF cultures)
oAn imbalance detected in cultures obtained in risk vs. control windows
oManual review of sample of charts showed no consistent pattern of concern (neonates
typically had reasons other than fever for cultures being done)
Slide 28
KAISER PERMANENTE INSTITUTE FOR HEALTH RESEARCH
Exposure -Dependent Events: Hypersensitivity Reactions
Nirsevimab Safety SurveillanceAdverse event Age group n Risk
window
(days)N cases
in risk
windowRate per
10K person
month
Anaphylaxis 0-37 days 9,855 0-2 0 0
38 days to <8
months28,054 0-2 0 0
Other allergic
reaction0-37 days 9,855 0-7 14 54.93
38 days to <8
months28,054 0-7 4 5.46
•Anaphylaxis and other allergic reactions: exposure -induced outcomes; only
assess within potential risk windows
•“Other allergic reaction” cases: n=17 with diagnosis code for urticaria and n= 1
“serum reaction” (also for urticaria); majority on same day as nirsevimab
Slide 29
Summary
Slide 30
KAISER PERMANENTE INSTITUTE FOR HEALTH RESEARCH
•Among a population of >74,000 (across two seasons) neonates and
infants exposed to nirsevimab :
oNo evidence of increased risk of seizures, ITP, drug reaction, fever and sepsis
oNo cases of anaphylaxis
oSmall number of cases of non -anaphylactic allergic reactions in both years,
primarily coded as urticaria
•Provides reassuring data regarding the safety profile of nirsevimab
when used in routine clinical practice
•Additional data extraction needed for late -season nirsevimab use;
findings preliminarySummary
Nirsevimab Safety Surveillance Slide 31
KAISER PERMANENTE INSTITUTE FOR HEALTH RESEARCH
•Three planned assessments
oAfter 2023 -2024 respiratory season
oPreliminary assessment 2024 -2025 season (through January, presented today)
oEnd of surveillance assessment (data extraction July 2025)
•Manual record review of any anaphylaxis cases
•Planned case -control study of autoimmune and immune complex
disease; however, appear to have too few cases to study this group of
outcomes at presentSurveillance Continues
Nirsevimab Safety Surveillance Slide 32
Questions?
Slide 33
KAISER PERMANENTE INSTITUTE FOR HEALTH RESEARCH
Doses by
Week, All
Formulations
Nirsevimab Safety Surveillance Slide 34
KAISER PERMANENTE INSTITUTE FOR HEALTH RESEARCH
Doses by
Week by
Formulation
Nirsevimab Safety Surveillance Slide 35
KAISER PERMANENTE INSTITUTE FOR HEALTH RESEARCH
•SmartVax (Western Australia):
o4,340 parents texted hyperlink to report adverse events (27.5% responded)
o18 (1.5%) respondents sought medical attention within 3 days of nirsevimab
oSymptoms at presentation included gastrointestinal issues, fatigue, local
reaction, fever, refusal to feed, unsettled behavior
oNo serious adverse events reported
•Maternity department, French hospital
oExposed accepted nirsevimab (n=477); unexposed declined (n=40)
oSurveyed at 2 hours, days 7, 14, 30
oMore frequent reports of regurgitation in nirsevimab -exposed on day 30Other Nirsevimab Safety Surveillance
Nirsevimab Safety SurveillanceRef: 1) Carcione D et al, PIDJ, 2025 (in press). 2) Ocana de Sentuary C et al, eClinicalMedicine 2025;79:102986
Slide 36
KAISER PERMANENTE INSTITUTE FOR HEALTH RESEARCH
•Misclassification of exposure: missing nirsevimab doses
•Misclassification of outcomes
•Safety assessment limited to pre -specified outcomes of interest
•Main analyses were regardless of vaccines received on same day; if
positive safety signal, can be difficult to disentangle effect of vaccines
from effect of nirsevimab
•Although risk and control windows are short, time -varying covariates
could bias results
•In a population size of >74,000, unable to assess risk of very rare
adverse eventsStudy Limitations
Nirsevimab Safety Surveillance Slide 37