Transcript Use of Synagis

Bronchiolitis and Synagis
Pretest

Which of the following children should receive RSV
prophylaxis during RSV season?
A. 5 month former 34 weeker who attends day care and has a 5
yo brother
B. 11 month former 27 weeker
C. 7 month former 31 weeker
D. 18 month patient with cystic fibrosis on home 02
E. 14 month Tetrology of Fallot patient
F. 22 month former 32 weeker with BPD who required diuretics
and steroids in October
CONTINUITY CLINIC
Background



Respiratory syncytial virus (RSV) is the
primary cause of lower respiratory tract
illness in young children.
Generally resolves uneventfully in otherwise
healthy children.
High risk populations may develop severe
and sometimes fatal lower respiratory tract
infections.
:
CONTINUITY
CLINIC
)
Background



RSV infection annually contributes up to
126,300 pediatric hospitalizations in the U.S.
Estimated annual hospitalization costs for
RSV pneumonia in children <=4 years: $300
- $400 million (1998 $), now much greater.
Annual mortality due to RSV in infants and
children is estimated to range from 200 to
over 2,700.
CONTINUITY CLINIC
Microbiology Basics


RSV is single-stranded RNA virus of
Paramyxoviridae family
Two subtypes, A and B
A subtypes cause more disease
 Within subtypes are several genotypes


Strains have shifts each year, accounting for reinfections
CONTINUITY CLINIC
Prematurity

Prematurity increases risk of severe RSV
infection. RSV Hospitalization Rate by Gestational Age at Birth
25%
20.60%
20%
Percent RSV
Hospitalization
14.60%
15%
11.30%
10%
6.40%
5%
0%
=< 26 W.
27 - 28 W.
> 28 - 30 W.
Gestational Age at Birth
CONTINUITY CLINIC
> 30 - 32 W.
Epidemiology

Worldwide RSV epidemics occur yearly




United States: November – April
Peak: January – March (most areas)
Peak: 2 – 3 months earlier (Southeast)
80% RSV admissions occur within 4 months
of discharge from NICU.
Respiratory Illness Hospitalization Rate by
Month of Discharge from NICU in Infants <= 32 Weeks GA
45%
42%
41%
40%
35%
30%
27%
Probability of 25%
hospitalization 20%
15%
15%
10%
5%
0%
Jan.
Feb. - Apr.
May - Aug.
Month of Discharge
CONTINUITY CLINIC
Sept. - Dec.
Transmission





Inoculation of nasal or ocular membranes after contact
with virus containing secretions or fomites
Virus can survive for several hours on hands and
fomites (WASH HANDS!!!)
Direct contact most common, large aerosol drops also
implicated
Incubation is 2-8 days
Patients usually shed 3-8 days but can shed up to 4
weeks in young infants
CONTINUITY CLINIC
Immunity




Almost everyone has been infected with RSV by age 3
Does not convey total protection against reinfection
Can be infected more than once in same RSV season
but usually 2d infection milder
Transplacental Ab does not protect completely against
infection but high Ab’s imply milder disease and usually
is only in upper respiratory tract
CONTINUITY CLINIC
Pathologic findings






Necrosis of epithelial cells
Proliferation of bronchiolar epithelium
Infiltrates of monocytes and T cells around arterioles
Neutrophils between vasculature and small airways
Leads to airway obstruction, air trapping, increased
airway resistance
Increased incidence of wheezing as children grow older
CONTINUITY CLINIC
Hospital therapy for RSV





Care is mainly supportive (fluids, respiratory
support)
Trial (one dose) of beta-agonist if
bronchospasm. D/C if not improvement
Steroids not recommended
Ribavirin not recommended unless severe LRT
infection
Neither RSVIG nor Synagis is effective in
treatment of hospitalized children
CONTINUITY CLINIC
RSVIG





Was developed as hyperimmune globulin from donors
with high titers of RSV antibody
In trials reduced hospitalizations in high risk infants by
41-63%
Increased morbidity and mortality in CHD patients
Interfered with immune response to live vaccines
(MMR and varicella)
No longer used frequently
CONTINUITY CLINIC
Palivizumab (Synagis)




Is monoclonal antibody (not blood product)
against RSV F glycoprotein
Easier to administer than RSVIG
Does not interfere with response to live vaccines
A newer but similar product is MEDI-524 or
Numax
More potent in animal trials
 Currently undergoing clinical evaluation

CONTINUITY CLINIC
Synagis



Synagis is available in 50 and 100 mg vials
The cost is $725 per 50 mg and $1370 per 100
mg vial
Synagis has a shelf life of 6 hours making
drug wastage nearly inevitable
CONTINUITY CLINIC
Dosing of Synagis
15 mg/kg IM once per month for 5 doses
 Begin before RSV season begins, October or
November
 Once dosing begins, continue even if patient is
past age of indication
 Continue even if breakthrough
infection

CONTINUITY CLINIC
Efficacy

IMpact-RSV trial in BPD pts and preemies


Trial in CHD pts




55% reduction in RSV-associated hospitalizations vs placebo
45% fewer hospitalizations
73% fewer hospital days needing O2
56% fewer total hospital days
Trial in 421 preemies without CLD who received
Synagis or placebo


50% fewer infants in Synagis group had recurrent wheezing
Shows that prevention of RSV LRTI may reduce risk of
recurrent wheezing in preemies without CLD
CONTINUITY CLINIC
Risk factors for severe disease

Less than 6 months






Underlying lung disease
Born before 35 weeks
Congenital heart disease
Immunocompromised patients




Born during first half of RSV season
Attending daycare
SCIDS, leukemia, BM transplant
Significant asthma (any age)
Living at altitudes greater than 8000 feet
Institutionalized elderly
CONTINUITY CLINIC
Adverse Reactions





Extremely safe, no serious adverse events in two
consecutive seasons seen
Severe hypersensitivity (less than 1 per 100,000)
About 1 per 100 children will have anti-Synagis
antibodies and antibody response declines with
continued dosing
No resistance to Synagis by RSV seen
Doesn’t interfere with immunizations
CONTINUITY CLINIC
Specific Recommendations



BPD- younger than 2 yo needing medical therapy for lungs who
required medical therapy within 6 mos of RSV season
CHD – under 2 who have hemodynamically significant CHD
Prematurity





≤ 28 weeks, younger than 1 yr at start of season
29-35 wks, younger than 6 mos
32-35 consider for infants <6 mos if 2 risk factors (day care attendance,
congenital abnormalities, NMD, school-aged sibs)
Immunocompromised – no controlled studies but seems
apparent that those with SCIDS or HIV with low CD4
undergoing chemotherapy or post-transplant would benefit
Structural or functional lung disease (such as CF) are at increased
risk; no data on effectiveness
CONTINUITY CLINIC
Medicaid and Synagis



Synagis is a benefit under the Comprehensive Care
Program
Administered by a Synagis provider
Eligibility for children under 2 the same except:

Hemodynamically significant heart disease is defined as
including:




Lung disease qualifies if:


Pulmonary hypertension
Digoxin or diuretics
Oxygen
On steroids, diuretics, ventilator or 02
Transplants patients qualify
CONTINUITY CLINIC
RSV Vaccine

Many challenges for effective vaccine




Immature immunity
Possible suppression of immune response by maternal
antibody
Several antigenically divergent strains
Live attenuated vaccines are being tested


Must be very attenuated in this young group
However, lessens chance of detectable Ab response
CONTINUITY CLINIC
Post-test

Which of the following children should receive RSV
prophylaxis during RSV season?
A. 5 month former 34 weeker who attends day care and has a 5
yo brother
B. 11 month former 27 weeker
C. 7 month former 31 weeker
D. 18 month patient with cystic fibrosis on home 02
E. 14 month Tetrology of Fallot patient
F. 22 month former 32 weeker with BPD who was required
diuretics and steroids in October
CONTINUITY CLINIC
Answer to Pretest Question
There is evidence for lack of benefit in
the 7 month old 31 weeker
No evidence for benefit in cystic fibrosis
patient but is reasonable to consider
CONTINUITY CLINIC
References



Up To Date, “Treatment and Prevention of RSV”
AAP Clinical Practice Guidelines, “Diagnosis and
Management of Bronchiolitis”, PEDIATRICS Volume
118, Number 4, October 2006
AAP Policy Statement, Revised Indications for the
Use of Palivizumab and Respiratory Syncytial
Virus Immune Globulin Intravenous for the
Prevention of Respiratory Syncytial Virus
Infections
CONTINUITY CLINIC