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RSV Prophylaxis:
Policy Change and Public Health Impact
Suzanne Staebler, DNP, APRN, NNP-BC
Assistant Director, Advanced Practice Nursing
Monroe Carell, Jr. Children’s Hospital at Vanderbilt
RSV Prophylaxis: Disclosures
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Conflict of Interest
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educational content about healthcare products or services of a
commercial interest with which she/he has a financial relationship
The speaker has declared no conflict of interest.
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RSV Prophylaxis: Disclosures (cont.)
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conjunction with this program.
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Accreditation Statement
Vanderbilt University Medical Center, Department of Nursing Education
and Professional Development is an approved provider of
continuing nursing education by the Tennessee Nurses
Association, an accredited approver by the American Nurses
Credentialing Commission on Accreditation.
RSV Prophylaxis: Objectives
• Discuss RSV risk categories and current evidence related to
Prophylaxis
• Compare and Contrast Prophylaxis guidelines (2007 and
2009) and potential impact on disease state
• Describe current advocacy effort related to RSV
Prophylaxis
Respiratory Development
RSV
High-Risk Categories for RSV
•
•
•
•
Preterm infants
BPD
Congenital Heart Defects
Immuno-compromised patients
Preterm Births United States
Percent
12.3
11.9
12
10.8
12.6
10.1
9.4
7.6
8
4
0
1981
1991
2001
2003
27 percent increase from 1981 to 2001
© 2006, March of Dimes
2007
March of
Dimes
Objective
2010
Healthy
People
Objective
High-Risk Categories for RSV
•
•
•
•
Preterm infants
BPD
Congenital Heart Defects
Immuno-compromised patients
Prevention is the Key
Researchers and yr (reference no.)
Location
No. of human
subjects
Rooney and Williams, 1971 (115)
Australia
62 (2–7 yrs of age)
A significant association of asthma in 56% of
children who subsequently experience wheeze
Gurwitz et al., 1981 (46)
Canada
48
Incidence of bronchial hyperreactivity is 57%
Hall et al., 1984 (49)
United States
29
An association between RSV infection and chronic
abnormalities of pulmonary function
Mok and Simpson, 1984 (85, 86)
United Kingdom
200
Welliver and Duffy, 1993 (141)
United States
43
Outcome/comment
Atopy and bronchial hyperreactivity independently
contribute to augmented response to RSV
postinfection
Decreased pulmonary function following
bronchiolitis is related to atopy
Sigurs et al., 1995 (126)
Sweden
47
Stein et al., 1999 (131)
United States
>180
RSV infection during first yr is an important risk for
asthma and allergy in the subsequent 2 yrs,
especially in genetically predisposed children
Lower respiratory tract RSV infections are
associated with increased risk of frequent wheeze
by age 6; risk decreased markedly with age and was
not significant by age 13
Sigurs et al., 2000 (125)
Sweden
47
RSV-induced bronchiolitis severe enough to cause
hospitalization is highly associated with the
development of asthma and allergic sensitization at
age 7.5 yrs
Prevention is the Key
There is no vaccine… but immunoprophylaxsis is available
• Synagis (palivizumab) is a humanized monoclonal antibody (IgG1κ)
produced by recombinant DNA technology
• Synagis exhibits neutralizing and fusion-inhibitory activity against
RSV. These activities inhibit RSV replication
Immunoprophylaxsis / Synagis Specifics
•
•
•
Mechanism of Action: Synagis exhibits neutralizing and fusioninhibitory activity against RSV. These activities inhibit RSV
replication
Pharmacokinetics: In pediatric patients < 24 months of age without
congenital heart disease (CHD), the mean half-life of Synagis was:
20 days and monthly intramuscular doses of 15 mg/kg
– achieved mean ± SD 30 day trough serum drug concentrations
of 37 ± 21 mcg/mL after the first injection
– 57 ± 41 mcg/mL after the second injection
– 68 ± 51 mcg/mL after the third injection
– 72 ± 50 mcg/mL after the fourth injection
Trough concentrations following the first and fourth Synagis dose
were similar in children with CHD and in non-cardiac patients
Immunoprophylaxsis / Synagis Trials
Safety and efficacy of Synagis were assessed in two randomized, doubleblind, placebo-controlled trials of prophylaxis against RSV infection in
pediatric patients at high risk of an RSV-related hospitalization
Trial 1:
Conducted during a single RSV season; n= total of 1,502 patients ≤ 24 months of
age with bronchopulmonary dysplasia (BPD) or infants with premature birth (≤ 35
weeks gestation) who were ≤ 6 months of age at study entry (7).
Trial 2:
Conducted over four consecutive seasons; n= total of 1287 patients ≤ 24 months
of age with hemodynamically significant congenital heart disease.
In both trials participants received 15 mg/kg Synagis or an equivalent volume of
placebo IM monthly for five injections and were followed for 150 days from
randomization
Immunoprophylaxsis / Synagis Trials
Table 1: Incidence of RSV Hospitalization by Treatment Group
Trial
Placebo
Synagis
Difference Between Groups
Relative Reduction
p-Value
Trial 1 Impact-RSV
N
Hospitalization
500
1002
53
48
(10.6%)
5.8%
55%
< .001
4.4%
45%
0.003
(4.8%)
Trial 2 CHD
N
Hospitalization
648
639
63
34
(9.7%)
(5.3%)
Immunoprophylaxsis / Synagis Trials
Table 1: Incidence of RSV Hospitalization by Treatment Group
Trial
Placebo
Synagis
Difference Between Groups
Relative Reduction
p-Value
Trial 1 Impact-RSV
N
Hospitalization
500
1002
53
48
(10.6%)
(4.8%)
BPD
12.8%
7.9%
Preemie/no BPD
8.1%
1.8%
5.8%
55%
< .001
Immunoprophylaxsis / Synagis Trials
Incidence of RSV Hospitalization by Treatment Group
Trial
Placebo
Synagis
648
639
63
34
(9.7%)
(5.3%)
Acyanotic
11.8%
7.9%
Cyanotic
7.9%
5.6%
Difference Between Groups
Relative Reduction
p-Value
Trial 2 CHD
N
Hospitalization
4.4%
45%
0.003
Immunoprophylaxsis / Synagis Specifics
Precautions
•
Synagis is for intramuscular use only…. give with caution to
patients with thrombocytopenia or any coagulation disorder.
•
The safety and efficacy of Synagis have not been demonstrated for
treatment of established RSV disease.
•
The most serious adverse reactions occurring with Synagis
treatment are anaphylaxis and other acute hypersensitivity
reactions.
•
Other adverse reactions most commonly observed in Synagistreated patients were upper respiratory tract infection, otitis media,
fever, rhinitis, rash, diarrhea, cough, vomiting, gastroenteritis, and
wheezing.
EBP Dosing Guidelines (2006-07)
< 32 weeks- dose
32-35wks- consider risk factors;
if 2+ present, dose for season
The rest of the story….
• The American Academy of Pediatrics Committee on Infectious
Diseases (COID) made revisions to the recommendations for
immunoprophylaxis (passive antibody protection) against RSV
Disease in the new publication of the RedBook guidelines
(summer 2009)…
– In an effort to balance cost versus benefits, these recommendations
from the COID limited dosing and chronological ages for intervention
in selected infants based on gestational ages at birth and published a
complex schedule of initiation and termination of dosing for primary
care providers… all contrary to the evidence in the RCTs
Cost-utility analysis of palivizumab in Italy: results from a
simulation model in the prophylaxis of respiratory syncytial
virus infection (RSV) among high-risk preterm infants
Based on the results of the present cost-effectiveness assessment it appears
realiable to state that compared to absence of prophylaxis, the
administration of palivizumab in preterm infants of varying gestational
ages, with or without complications, does improve survival (qualityweighted or not) at reasonable costs in terms of resources covered by the
NHS, when compared to internationally accepted threshold values.
However, there is not general consensus concerning palivizumab prophylaxis for
preterm infants born between 32 and 35 weeks of gestational age without chronic
lung disease and haemodynamically significant congenital heart disease.
Italian Journal of Pediatrics 2009, 35:4 doi:10.1186/1824-7288-35-4
The rest of the story….
NEW
ORIGINAL
2009 Redbook Guidelines
32-35 wk preterm infants1
Clinical trials and Synagis® Package Insert
Research-based data (2006 guidelines)2
GA eligibility:
For prophylaxis, defined as
32 wks, 0 d to 34 wks, 6d.
35 week infants are excluded
Safety and efficacy were established
in infants with a history of
premature birth who were <35 GA
Age cutoff:
Eligibility criteria of < 3 months
of age at start of RSV season
or born during RSV season
The phase III trial included preterm
infants who were < 6 months of
age at the beginning of the season.
Dosing:
Maximum of 3 doses:
Stop dosing when infant is
90 days of age even if this
occurs during the RSV season
This means that many infants
will receive only 1 or 2 doses.
The efficacy and safety of
Synagis® has only been evaluated
using monthly doses throughout
the entire RSV season. 5 monthly
doses were given in Phase III
trials.
Risk Factors:
Must have 1 of 2 risk factors:
Day care attendance or
Sibling < 5 years of age.
Must have 2 of 5 previously listed
risk factors.
The rest of the story…. Advocating for our patients
Healthcare provider and public ‘uprising’ and petition to
the CDC to intervene…
•Advisory Committee on Immunization Practices
(ACIP) convened RSV work-group to evaluate issue
National Perinatal Association:
Respiratory Syncytial Virus Prevention 2010
Position Statement (published Spring 2010)
The rest of the story…. Advocating for our patients
NANN/NANNP:
Leading advocacy effort on behalf of nurses caring for
these patients…
•Member alert on Advocacy list-serv
•Information sessions at national meeting (Sept
2010)
•On-line petition
•Consensus building with other nursing
organizations (NAPNAP, AWHONN, SPN)
•Represented NANN and NAPNAP members at Oct
CDC ACIP meeting
The rest of the story…. Advocating for our patients
NANN/NANNP:
•On-line petition…
“We believe that recent changes in the AAP guidelines for
immunoprophylaxis (passive antibody protection) leave
many fragile infants vulnerable by reducing the number of
doses they can receive during the RSV season. We
believe that denial of full seasonal coverage on the basis
of gestational age, without consideration of other risk
factors, is discriminatory to a select population of expremature infants and may put certain populations at even
greater risk as a result of healthcare disparities.”
The rest of the story…. Advocating for our patients
The rest of the story…. Advocating for our patients
National Medical Association and National Black Nurses Association
Consensus Panel Paper: Respiratory Syncytial Virus and African
Americans
“The recent proposed change to the FDA approved dosage may have an
unintended consequence of disproportionately affecting African American infants.
Not only are African Americans over‐represented among infants who are premature
and/or low birth weight, they are also over‐represented within the ranks of almost
all other RSV risk factors,”
5 state Medicaid programs have continued to dose using the
2006-07 dosing guidelines based on risk factors
The rest of the story…. Advocating for our patients
American Lung Association
November is National Prematurity Awareness Month
November is National Prematurity Awareness Month and the American Lung Association is raising
awareness about a virus that has an impact on this country’s most vulnerable patient population: infants
and small children.
Respiratory Syncytial Virus (RSV) infection causes pneumonia and acute bronchiolitis, particularly during
fall and winter. In fact, RSV is so common that it affects almost all children by their second birthday. For
older children, the symptoms are like those of a mild cold. However about 75,000 to 125,000 children
under a year old get very sick and are hospitalized with RSV infection each year.
The major risk factors for serious RSV infection are pre-existing conditions such as chronic lung disease
and congenital heart disease. However, research also points to two additional RSV risk factors:
prematurity and living with people who smoke. A study found that there are 22,000 hospitalizations of
children from RSV each year related to parental secondhand smoke.
Much of this is preventable. The U.S. Surgeon General has concluded there is no safe level of exposure
to secondhand smoke. It is a risk factor not only for acute respiratory infections such as RSV bronchitis
and pneumonia but also sudden infant death syndrome (SIDS), ear problems and asthma attacks for
children.
Premature infants exposed to secondhand smoke are particularly at risk because of underdeveloped
defenses. Secondhand smoke can increase the potential severity of a commonplace infection like
RSV—and severely impact the health of infants and small children nationwide. So, it’s critical for all
homes to be smokefree.
Next steps…. Advocating for our patients
Next steps…. Advocating for our patients
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National Association of Neonatal Nurses / National Association of Neonatal Nurse
Practitioners
Latest on RSV: www.nann.org
American Academy of Pediatrics
RSV: Brief Overview
American Lung Association
Understanding RSV Disease
Centers for Disease Control and Prevention
Respiratory Syncytial Virus
National Institute of Allergy and Infectious Diseases
Respiratory Syncytial Virus
National Library of Medicine/National Institutes of Health
MedlinePlus: RSV
Questions?