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supplement

SUPPLEMENT TO
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Respiratory Syncytial Virus (RSV)
Prevention Strategies and the Appropriate
Identification of Vulnerable Populations
Based on an RSV Expert Panel, Aug. 18, 2008, Chicago
HIGHLIGHTS
• RSV in the Pediatric Population
• In the Trenches: A Pediatrician’s Perspective on
Implementation, Prevention, and Treatment Strategies
• RSV in the Adult Population
• Medical Director Considerations
• Pharmacy Director Considerations
• RSV Issues and Solutions
This activity is sponsored by The Chatham Institute
Volume 17, No.11
Supplement 12
November 2008
This activity is supported by an educational grant
from MedImmune
WELCOME
INTRODUCTION
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Managed Care Considerations:
Vulnerable Populations and Prevention Strategies
For Respiratory Syncytial Virus Disease
STEVEN R. PESKIN, MD, MBA
Chief Medical Officer
The Chatham Institute, Chatham, New Jersey
espiratory syncytial virus (RSV) is a source of substantial morbidity in the very young and the very old. For children younger
than 1 year, serious RSV infection of the lower respiratory tract
may require hospitalization for bronchiolitis or pneumonia, and for premature infants, the services of a neonatal intensive care unit. Among the
elderly, RSV often is active at the same time as influenza and appears to
be responsible for some of the deaths attributed to influenza.
There is no treatment for RSV infection, so prophylactic measures are
the key to protecting high-risk populations. For the elderly, commonsense precautions like washing hands and minimizing visits from small
children can break the transmission of RSV. For infants, immunoprophylaxis with palivizumab (Synagis) is available. Palivizumab is a humanized monoclonal antibody that binds with a protein on the surface of the
virus, effectively neutralizing it. The drug, however, does not elicit any
immune response that confers lasting protection — palivizumab is the
protection. To be effective, it must be administered prior to the beginning of an RSV season and every 30 days thereafter for the duration of
the season. For high-risk infants, such as infants younger than 35 weeks
gestational age, immunoprophylaxis with palivizumab should be administered before hospital discharge and then throughout the infant’s first
RSV season.
These considerations raise several challenges for physicians and for
medical directors and pharmacists in managed care organizations:
Quickly identifying those infants at high risk for whom immunoprophylaxis is appropriate; knowing when the RSV season is likely to begin in
a given locale; administering the first dose prior to the RSV season; and
making sure that patients adhere to therapy.
These and related issues were addressed by an RSV Expert Panel convened by The Chatham Institute this past August in Chicago. The articles in this supplement are an outgrowth of that panel and present the
perspectives of practicing physicians, a pediatrician, and managed care
executives.
R
Disclosure: Steven R. Peskin, MD, MBA, has no real or apparent conflicts of interest
with respect to companies, organizations, or proprietary products mentioned in this
supplement.
This supplement is supported by an educational grant from MedImmune. The material in this supplement has been independently peer
reviewed. The grantor played no role in reviewer selection.
Opinions are those of the authors and do not necessarily reflect those of the institutions that employ them, or of MedImmune; The
Chatham Institute; MediMedia USA; or the publisher, editor, or editorial board of MANAGED CARE.
Clinical judgment must guide each clinician in weighing the benefits of treatment against the risk of toxicity. Dosages, indications, and
methods of use for products referred to in this supplement may reflect the clinical experience of the authors or may reflect the professional
literature or other clinical sources and may not be the same as indicated on the approved package insert. Please consult the complete prescribing information on any products mentioned in this publication.
MediMedia USA assumes no liability for the material published herein.
S U P P L E M E N T
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November 2008
Respiratory Syncytial Virus (RSV)
Prevention Strategies and the Appropriate
Identification of Vulnerable Populations
Based on an RSV Expert Panel, Aug. 18, 2008, Chicago
A Continuing Education Activity
INTRODUCTION
Managed Care Considerations: Vulnerable Populations and
Prevention Strategies for Respiratory Syncytial Virus Disease ........Opposite
STEVEN R. PESKIN, MD, MBA
FACULTY PRESENTATIONS
RSV Disease in the Pediatric Population:
Epidemiology, Seasonal Variability, and Long-Term Outcomes ..................3
ERIC A. F. SIMÕES, MD, DCH
In the Trenches: A Pediatrician’s Perspective on Prevention
and Treatment Strategies for RSV Disease ....................................................7
MICHAEL P. FROGEL, MD
RSV Infection in the Adult Population .......................................................13
JULIO A. RAMIREZ, MD, FACP
Health Plan Medical Director: Considerations for Prevention
and Management of RSV Disease.................................................................15
ALBERT TZEEL, MD, MHSA
Health Plan Pharmacy Director: Considerations for Treatment
and Management of RSV Disease.................................................................17
DOUGLAS S. BURGOYNE, PHARMD, RPH
ROUNDTABLE
RSV Issues and Solutions..............................................................................18
CONTINUING EDUCATION
Continuing Education Objectives...........................................................................................2
Assessment/Evaluation/Certificate Request ........................................................................20
Post-Test .................................................................................................................................21
SELF-STUDY CONTINUING EDUCATION ACTIVITY
Respiratory Syncytial Virus (RSV):
Prevention Strategies and the Appropriate Identification of Vulnerable Populations
Overview/needs assessment
Respiratory syncytial virus (RSV) is a
common and easily transmitted disease
that affects young children and is the leading cause of hospitalization of infants
younger than 1 year of age. It is estimated
that in the United States, up to 126,000 infants are hospitalized each year because of
severe RSV disease, and that close to 20
percent of these are premature infants. RSV
disease is also a risk factor for the development of respiratory ailments and physician-diagnosed asthma in later life.
RSV is costly. A single hospitalization can
cost more than $5,000 a day for a child in
need of respiratory assistance, and the
high cost of immunoprophylaxis limits its
use to those infants at highest risk of complications from RSV infection. RSV infection
also is common among the elderly and the
immunocompromised and, together with
influenza virus, is the most common cause
of hospital admissions for adults with
chronic cardiac and pulmonary disorders
and acute respiratory failure.
This Continuing Medical Education program provides current information on our
understanding of RSV seasonality, vulnerable populations, preventive strategies, and
the therapeutic approaches available to
manage RSV.
Target audience
This program is targeted to medical directors, physicians, and pharmacists in
managed care organizations.
Educational objectives
After reading this publication, participants will be able to:
• Explain the epidemiology, burden of disease, and seasonal and regional variability of RSV.
• Discuss the economic impact of RSV on
the health care system.
• Explain which populations are at high risk
of RSV infection and why.
• Discuss current and new prophylactic
options for managing RSV.
• Establish educational initiatives to raise
the awareness of parents and health care
professionals about the prevention and
treatment of RSV.
• Assess best practices in a managed care
setting for managing RSV, so as to improve outcomes.
2
Method of instruction
Participants should read the learning
objectives and review the activity in its entirety. After reviewing this activity, submit
a completed post-test and evaluation.
Upon achieving a passing score of 70 percent or better on the post-test, a statement of credit will be awarded.
Accreditation and designation
This activity has been planned and implemented in accordance with the Essential
Areas and policies of the Accreditation
Council for Continuing Medical Education
through the sponsorship of The Chatham
Institute. The Chatham Institute is accredited by the ACCME to provide continuing
medical education for physicians. The
Chatham Institute designates this educational activity for a maximum of 1.50 AMA
PRA Category 1 Credits.TM Physicians should
claim credit commensurate with the extent
of their participation in the activity.
The Chatham Institute is accredited by the Accreditation
Council for Pharmacy Education (ACPE) as a provider of
continuing pharmacy education. This
program is approved for 1.50 contact hours
(0.150 CEU) of continuing education for
pharmacists.
ACPE Universal Program Number (UPN):
812-000-08-024-H01-P
Release Date: Nov. 20, 2008
Expiration Date: Nov. 20, 2009
Medium: Journal supplement
Planning committee members
Douglas Burgoyne, PharmD, RPh; Michael
P. Frogel, MD; Julio A. Ramirez, MD, FACP;
Eric A.F. Simões, MD, DCH; Albert Tzeel, MD,
MHSA; Steven R. Peskin, MD, MBA, medical
director, The Chatham Institute; Katherine T.
Adams, editor.
MANAGED CARE / SUPPLEMENT
Conflict-of-interest policy and disclosures of significant relationships
It is the policy of The Chatham Institute
to ensure balance, independence, objectivity, and scientific rigor in all of its educational programs. The Chatham Institute requires the disclosure of any significant
financial interest or any other relationship a
facility member may have with the manufacturer(s) of any commercial product(s) or
device(s). Further, faculty members are required to disclose discussion of any offlabel uses in their presentation. Any faculty
members not complying with the disclosure policy are not permitted to participate
in the educational activity.
All program content has been peer reviewed for balance and any potential bias.
Peer reviewers of this program have no real
or apparent conflicts of interest to report
with respect to the content of this publication. The process to resolve conflicts of interest aims to ensure that financial relationships with commercial interests and
resultant loyalties do not supersede the
public interest in the design and delivery of
continuing medical activities for the profession.
The faculty of this program and the editorial staff of this monograph have disclosed the following:
Michael P. Frogel, MD: grant and research
support and speaker’s bureau , MedImmune.
Julio Ramirez, MD, FACP: grant and research support from Pfizer, Cubist Pharmaceuticals, Merck & Co., and Wyeth Pharmaceuticals; speaker’s bureau for Pfizer, Cubist
Pharmaceuticals, Merck & Co., Ortho-McNeil,
and Schering-Plough.
Eric S. F. Simões, MD, DCH: Grant and research support and speaker’s Bureau, MedImmune and Abbott.
Douglas Burgoyne, Pharm D, RPh: Honoraria from Eli Lilly, GlaxoSmithKline, and Abbott.
Albert Tzeel, MD, MHSA; Steven R. Peskin,
MD, MBA, The Chatham Institute; and
Katherine T. Adams, editor, report no real or
apparent conflict of interest with respect to
the content of this publication.
Program sponsorship and support
This activity is sponsored by The
Chatham Institute, and is supported by an
educational grant from MedImmune.
RSV Disease in the Pediatric Population:
Epidemiology, Seasonal Variability,
And Long-Term Outcomes
ERIC A. F. SIMÕES, MD, DCH
Professor of Pediatrics, Division of Infectious Diseases
University of Colorado Denver Health Sciences Center and The Children’s Hospital, Denver
By the age of 2 years, most children will have acquired
fines the onset of an RSV season as the first of 2 consecua respiratory syncytial virus (RSV) infection (Glezen
tive weeks during which the median percentage of speci1986). For most of these children, the RSV infection will
mens testing positive for RSV antigen is 10 percent or
be unremarkable, but a subset of children, notably infants
greater, and offset is the last of 2 consecutive weeks when
born prematurely or with congenital heart disease
the median percentage of positive specimens is 10 per(CHD), is at an increased risk for severe RSVcent or greater (CDC 2007). When analyzed by
associated lower respiratory tract infection
these definitions in terms of the broad U.S.
(LRTI), particularly bronchiolitis. In the
census regions (Northeast, South, Midwest,
United States, up to 126,000 infants are hospiWest), it has been found that the RSV season
talized each year because of severe RSV disease
varies from region to region and within any
(Shay 1999). Additionally, from 1990 through
given region from year to year (Panozzo 2007).
1999, the estimated annual number of RSVThe South has the earliest onset (median onset
associated deaths was 235. Ninety-four perin late November [week 47], with a range from
cent of these deaths occurred in infants,
week 41 to week 51), and the longest duration
accounting for 5.3 deaths per 100,000 person(16 weeks; range, 13–20 weeks). The Midwest
ERIC A. F.
years among infants and 0.2 deaths per 100,000
has the latest onset (median onset in early JanSIMÕES, MD,
person-years among children aged 1 to 4
uary [week 1], with a range from week 50 to
DCH
(Thompson 2003).
week 5) and the shortest duration (13 weeks;
range 10–16 weeks). The Figure on page 4 shows reRSV seasonality
gional RSV trends from July 2000 through July 2006.
Analyses within states show substantial variations in
The RSV season in the United States, as acknowledged
RSV seasonality, which are lost in regional reports. In the
by the American Academy of Pediatrics (AAP), generally
southwest, northwest, and north regions of Florida, for
extends from November through March with a peak in
example, RSV seasons range from 7 to 8 months, while
January or February (AAP 2006), but considerable geoin central and southeastern Florida, the RSV seasons last
graphic and temporal variation in RSV seasonality exists.
11 or 12 months (Light 2008).
The Centers for Disease Control and Prevention deIn Colorado, we have analyzed 10 years of RSV hosEric A. F. Simões, MD, DCH, received his MD from the Univerpitalization data at the local level using ZIP code tabulation areas (ZCTAs), which are comparable to ZIP codes,
sity of Madras, India, in 1984 and obtained his Fellowship in Peand we have noticed considerable geographic and temdiatric Infectious Disease from the University of Colorado Health
poral variations (Zachariah 2008). In some locales, the
Sciences Center. He has been an invited speaker at numerous naRSV seasons lasted only 3 months, whereas in others, the
tional and international symposia, and has been a guest editor and
seasons exceeded 5 months. For about one third of all
reviewer for more than 30 journals. Simões has been involved with
Colorado children, the RSV season is less than 5 months,
the Integrated Management of Childhood Illness, a program debut for another third, the RSV season lasts 6 or 7 months,
veloped by the World Health Organization (WHO) to reduce
i.e., comparable to much of Florida. We also have found
childhood and infant mortality in the developing world, and is a
that local weather conditions affect RSV activity through
scientific consultant for the WHO Division of Child and Adolescomplex interactions of temperature and humidity
cent Health and Development. Simões’ research interests focus on
(Yusuf 2007), and we speculate that this might affect the
the epidemiology and prevention of acute respiratory infections,
stability of the virus in the large-particle aerosols or
specifically RSV and Streptococcus pneumoniae.
SUPPLEMENT / RSV
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FIGURE
U.S. regional RSV trends, July 2000 through July 2006
Positive RSV tests (%)
50
40
30
20
10
7/1/2000
8/26/2000
10/21/2000
12/16/2000
2/10/2001
4/7/2001
6/2/2001
7/28/2001
9/22/2001
11/17/2001
1/12/2002
3/9/2002
5/4/2002
6/29/2002
8/24/2002
10/19/2002
12/14/2002
2/8/2003
4/5/2003
5/31/2003
7/26/2003
9/20/2003
11/15/2003
1/10/2004
3/6/2004
5/1/2004
6/26/2004
8/21/2004
10/16/2004
12/11/2004
2/5/2005
4/2/2005
5/28/2005
7/23/2005
9/17/2005
11/12/2005
1/7/2006
3/4/2006
4/29/2006
6/24/2006
0
South
North
West
Midwest
Source: Panozzo CA. Pediatr Infect Dis J. 2007. Reprinted with permission.
human secretions through which RSV is believed to be
transmitted. We also have found that cyclical levels of maternal serum anti-RSV antibody, as reflected by cord
blood RSV-neutralizing antibody, precede the onset and
end of the RSV season for infants, suggesting a role for
the decline of maternal RSV antibodies in the susceptibility of newborn infants to RSV and the increase in the
levels that presage the end of the epidemic (Stensballe
2008).
Risk factors
Although most infants acquire an RSV infection during their first RSV season, and although most of those infections are relatively mild, certain infants are at increased risk for severe RSV disease (Welliver 2003). Those
at high risk include premature infants, children with
chronic lung disease (CLD) or CHD, and children who
are immunosuppressed because of transplants or chemotherapy (Simões 2003, Welliver 2003). Environmental
and demographic risk factors for severe RSV disease are:
birth during the first half of the RSV season; a gestational
age (GA) of 35 weeks or less; the first 6 weeks of life; male
sex; household crowding (e.g., sharing a bedroom with
siblings); and attending day care with five or more children (Simões 2003). There also is good evidence for exposure to indoor tobacco smoke (Carroll 2007, Simões
2007a) but equivocal evidence for breast feeding for less
than 2 months, and no evidence that low maternal education or malnutrition are risk factors. In Colorado, we
have found that living at a high altitude (above 2,500 m)
increases the risk of RSV-associated hospitalization; the
effect of altitude is more pronounced in children aged 1
to 4 years than in infants (Choudhuri 2006).
In the United States, 10 percent of premature infants
4
are born at a GA of 28 completed weeks or less, 20 percent between 28 and 31 weeks, and 70 percent between
32 and 35 weeks (Ventura 1996). For preterm infants with
underlying CLD, RSV-associated LRTIs are associated
with increased morbidity and higher mortality rates and
a higher reinfection rate (Navas 1992). In preterm infants
without underlying CLD, RSV-associated LRTIs are associated with a hospitalization rate approaching 10 percent and increased morbidity (Simões 2002).
Using various risk factors, my colleagues and I have developed a model to predict which premature infants
(33–35 weeks GA) are at highest risk for RSV hospitalization (Simões 2008). This model is intended to facilitate the effective and responsible use of palivizumab
(Synagis), a humanized monoclonal antibody used for
immunoprophylaxis in this population. We began with
a set of 15 risk factors based on those identified in a
Spanish case-control study (Figueras-Aloy 2004), but
we were able to make the model easier to use by reducing the number of variables to eight without loss of sensitivity, specificity, or predictive value. This model has a
sensitivity and specificity of 72 percent in predicting
RSV hospitalization.
Long-term outcomes
Although hospitalization is a major outcome of severe
RSV infections, it is not the only outcome. One important long-term outcome, which is largely unrecognized,
is the development of wheezing later in life.
The relationship of early viral infection to specific
wheezing phenotypes is a matter of some controversy,
but it has raised these critical questions: Does severe
RSV-associated LRTI cause the differences in pulmonary
sequelae that have been observed in longitudinal stud-
ies? Do inherent abnormalities that predispose a child to
wheeze later in life also predispose the child to develop
a severe RSV LRTI?
The causal relationship of early RSV infection to later
wheezing seemed to be supported by a study conducted
by Stein (1999) in which a cohort of 207 children who
had an RSV-associated lower respiratory tract illness
during the first 3 years of life were prospectively followed for up to 13 years. Their risk for frequent or infrequent wheeze was increased up to the age of 11 years
compared with children who had no lower respiratory
tract illness during their first 3 years. For infrequent
wheeze, the adjusted odds ratios were 3.2, 2.5, and 1.7 at
age 3, 6, and 11 years, respectively, and for frequent
wheeze, 4.3, 1.9, and 2.4 at the same time points. All
these odds ratios were statistically significant (P<.05), except for frequent wheeze at 6 years.
Conflicting results emerged from a study conducted
by Lemanske (2005) in which a cohort of newborns were
followed for up to 3 years. To be enrolled in this study,
an infant needed to have at least one parent with respiratory allergies, or a history of physician-diagnosed
asthma, or both. After stratifying by the severity of RSV
illness, the percentage of children wheezing in their third
year of life was most strongly associated with the severity of rhinovirus wheezing illnesses during infancy rather
than the severity of RSV illnesses. More recently, this association was found to exist up until the age of 6 years
(Jackson 2008).
My colleagues and I conducted a nested (1:5) casecontrol study (Stensballe 2006) in Denmark of 2,564
children under 18 months of age with RSV hospitalization compared with 12,816 control children who had
been prospectively followed from birth to 18 months of
age without RSV hospitalization as participants in the
Danish national birth cohort. The point estimates of the
adjusted relative risk (RR) of RSV hospitalization were
1.11 for maternal atopic dermatitis, 1.72 for maternal
asthma, and 1.23 for paternal asthma. Infrequent wheezing in the child was associated with an RR of subsequent
hospitalization of 2.98 and recurrent wheezing with an
RR of 5.90. We concluded that asthmatic disposition
and wheezing were strong determents of subsequent
RSV hospitalization in Danish children less than 18
months of age. In this study, up to a third of children had
experienced wheezing prior to RSV hospitalization.
Our subsequent studies of RSV immunoprophylaxis
have addressed the role of RSV in the causation of subsequent recurrent wheezing. These studies also provide
insight into resolving this apparent conundrum. In one
such study (Wenzel 2002), we evaluated pulmonary function and atopy in 13 children at high risk for respiratory
disease 7 to 10 years after they had received immunoprophylaxis with RSV immunoglobulin. We compared them
with 26 high-risk controls matched for age and GA. The
children who had received RSV immunoprophylaxis had
better lung function and less atopy than the control
group. This small study suggests that preventing or blunting RSV infections might decrease the risk for asthma
later in life, but larger prospective studies of children at
high risk for asthma are warranted to confirm this association. Following that study, we conducted a multicentered study (Simões 2007b) in Europe and Canada
using palivizumab. Beginning at a mean age of 19
months, we prospectively followed for 24 months a cohort of preterm infants who had received RSV immunoprophylaxis with 3 or more doses of palivizumab in infancy and who never had been hospitalized for RSV
(n=191) and a cohort who never received palivizumab
(n=230), including 76 who were hospitalized for RSV and
154 who were not. The mean GA in the palivizumabtreated and the untreated groups was 29.9 and 31.4
weeks, respectively. At follow up at 4 to 5 years of age, the
proportion of children with recurrent wheezing was reduced by 49 percent in the palivizumab-treated group
relative to the proportion in the untreated group (13
percent [25/191] versus 26 percent [59/230]; P=.001).
Likewise, there was a relative reduction of 51 percent in
the palivizumab-treated group in the proportion of children with physician-diagnosed recurrent wheezing (8
percent [15/191] versus 16 percent [37/230]; P=.011).
Taken together, our studies in Europe and in the
United States have shown that in up to a third of children
with RSV hospitalization, an atopic disposition may be
responsible for the hospitalization. In preterm infants, we
have shown that RSV infection may cause up to 50 percent of the recurrent wheezing seen at the age of 3 to 4
years. How long this wheezing continues is unknown;
however, a study in Tucson, Ariz., (Stein 1999) suggests
that in normal infants, RSV infection in the first 3 years
of life predisposes them to recurrent wheezing up to 11
years of age but disappears by age 13. In children with a
strong atopic background, rhinovirus rather than RSV
may be a more important inciting factor for the development of asthma seen at 6 years of age (Jackson 2008).
Summary
Infants younger than 1 year, and especially premature
infants, are susceptible to severe RSV disease, which accounts for up to 126,000 hospitalizations each year. In the
United States, the RSV season generally extends from November though March, but varies considerably both temporally and geographically. Studies, such as the one we
have conducted in Colorado, indicate that the RSV season can even vary among local communities. In addition
to seasonal variability, other independent risk factors
also have to be taken into consideration when considering RSV immunoprophylaxis. Among these are a GA of
less than 33 weeks, infants with CLD or CHD or who are
immunosuppressed, male sex, household crowding, and
SUPPLEMENT / RSV
5
daycare attendance. Exposure to indoor tobacco smoke
and abbreviated breast feeding (less than 2 months) also
may be pertinent risk factors. The Colorado studies show
that high altitude also increases the risk of RSV hospitalization.
Although hospitalization is a major outcome of severe
RSV infections in infants, the development of wheezing
and physician-diagnosed asthma later in life may be a
long-term outcome that should be considered.
References
AAP (American Academy of Pediatrics). Respiratory syncytial
virus. In: Pickering LK, Baker CJ, Long SS, McMillan JA,
eds. Redbook: 2006. Report of the Committee on Infectious
Diseases. 27th ed. Elk Grove Village, Ill.: American Academy
of Pediatrics; 2006:560–566.
Carroll KN, Gebretsadik T, Griffin MR, et al. Maternal asthma
and maternal smoking are associated with increased risk of
bronchiolitis during infancy. Pediatrics. 2007;19:
1104–1112.
CDC (Centers for Disease Control and Prevention). Brief report: respiratory syncytial virus activity–United States, July
2006-November 2007. MMWR Morb Mortal Wkly Rep.
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Choudhuri JA, Ogden LG, Ruttenber AJ, et al. Effect of altitude
on hospitalizations for respiratory syncytial virus infection.
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Figueras-Aloy J, Carbonell-Estrany X, Quero J; IRIS Study
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Glezen WP, Taber LH, Frank AL, Kasel JA. Risk of primary infection and reinfection with respiratory syncytial virus. Am J
Dis Child. 1986;140:543–546.
Jackson DJ, Gangnon RE, Evans MD, et al. Wheezing rhinovirus
illnesses in early life predict asthma development in high
risk children. Am J Respir Crit Care Med. June 19, 2008.
Epub ahead of print.
Lemanske RF Jr, Jackson DJ, Gangnon RE, et al. Rhinovirus illnesses during infancy predict subsequent childhood
wheezing. J Allergy Clin Immunol. 2005;116:571–577.
Light M, Bauman J, Mavunda K, et al. Correlation between respiratory syncytial virus (RSV) test data and hospitalization
of children for RSV lower respiratory tract illness in
Florida. Pediatr Infect Dis J. 2008;27:512–518.
Navas L, Wang E, de Carvalho V, Robinson J. Improved outcome
of respiratory syncytial virus infection in a high-risk hospitalized population of Canadian children. J Pediatr. 1992;
121:348–354.
Panozzo CA, Fowlkes AL, Anderson LJ. Variation in timing of
respiratory syncytial virus outbreaks: lessons from national
surveillance. Pediatr Infect Dis J. 2007;26(11suppl):
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Shay DK, Holman RC, Newman RD, et al. Bronchiolitisassociated hospitalizations among US children, 1980–1996.
JAMA. 1999;282:1440–1446.
Simões EA. Environmental and demographic risk factors for
respiratory syncytial virus lower respiratory tract disease.
J Pediatr. 2003;143(5 suppl):S118–S126.
Simões EA. Immunoprophylaxis of respiratory syncytial virus:
global experience. Respir Res. 2002;3(suppl 1):S26–S33.
Simões EA. Maternal smoking, asthma, and bronchiolitis: clearcut association or equivocal evidence? Pediatrics. 2007a;
119:1210–1212.
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Simões EA, Carbonell-Estrany X, Fullarton JR, et al; European
RSV Risk Factor Study Group. A predictive model for respiratory syncytial virus (RSV) hospitalization of premature
infants born at 33-35 weeks of gestational age, based on
data from the Spanish FLIP study. Resp Res. 2008 (in press).
Simões EA, Groothuis JR, Carbonell-Estrany X, et al.,
Palivizumab Long-Term Respiratory Outcomes Study
Group. Palivizumab prophylaxis, respiratory syncytial
virus, and subsequent recurrent wheezing. J Pediatr. 2007b
151:34–42.
Stein RT, Sherrill D, Morgan WJ, et al. Respiratory syncytial virus
in early life and risk of wheeze and allergy by age 13 years.
Lancet. 1999;354:541–545.
Stensballe L, Ravn H, Kristensen K, et al. Seasonal variation of
maternally derived respiratory syncytial virus antibodies
and association with infant hospitalizations for respiratory
syncytial virus. J Pediatr. 2008 (in press).
Stensballe LG, Kristensen K, Simões EA, et al.; Danish RSV Data
Network. Atopic disposition, wheezing and subsequent respiratory syncytial virus hospitalization in Danish children
younger than 18 months: a nested case-control study. Pediatrics. 2006;118:1360–1368.
Thompson WW, Shay DK, Weintraub E, et al. Mortality associated with influenza and respiratory syncytial virus in the
United States. JAMA. 2003;289:179–186.
Ventura SJ, Martin JA, Mathews TJ, Clarke SC. Advance report of
final natality statistics, 1994. Monthly vital statistics report.
Hyattsville, Md.: National Center for Health Statistics.
1996;44:11(suppl).
Welliver RC. Review of epidemiology and clinical risk factors for
severe respiratory syncytial virus (RSV) infection. J Pediatr.
2003;143(5 suppl):S112–S117.
Wenzel SE, Gibbs RL, Lehr MV, Simões EA. Respiratory outcomes in high-risk children 7 to 10 years after prophylaxis
with respiratory syncytial virus immune globulin. Am J
Med. 2002;112:627–633.
Yusuf S, Piedimone G, Auais A, et al. The relationship of meteorological conditions to the epidemic activity of respiratory
syncytial virus. Epidemio Infect. 2007;135:1077–1090.
Zachariah P. Personal communication. Sept. 29, 2008.
Disclosures: Eric A. F. Simões, MD, DCH, has received grant and
research support related to palivizumab from MedImmune and
serves on MedImmune’s speaker’s bureau. He also has received
grant and research support from Abbott and serves on Abbott’s
speaker’s bureau.
In the Trenches: A Pediatrician’s
Perspective on Prevention and
Treatment Strategies for RSV Disease
MICHAEL P. FROGEL, MD
Associate Professor of Pediatrics, Albert Einstein College of Medicine, New York City
Chief, General Pediatrics and Sports Medicine, and Director of the Urgi-Center, Schneider Children’s Hospital,
North Shore Long Island Jewish Health System, New Hyde Park, N.Y.
Respiratory syncytial virus (RSV) bronchiolitis is the
leading cause of hospitalization of infants younger than
1 year (Figure). Between 1980 and 1996, the rate of hospitalization for bronchiolitis in children younger than 6
months increased 2.4-fold (Shay 1999). More recent estimates place the rate of RSV hospitalization in infants
younger than 1 year at 24.3 per 1,000, with annual RSV
hospital costs exceeding $1.1 billion (McLaurin 2005).
Palivizumab (Synagis) is a U.S. Food and Drug Administration-approved monoclonal antibody that is administered intramuscularly to prevent severe RSV disease in
high-risk infants. Although timely immunoprophylaxis
with palivizumab can reduce RSV hospitalizations and
morbidity in high-risk populations, pediatricians who provide immunoprophylaxis face numerous challenges, such
as reimbursement obstacles and achieving continuity of
care. In this article, I discuss those challenges from the perspective of a practicing pediatrician at a children’s hospital.
Premature infants at high risk
Children at high risk of RSV disease include infants
born prematurely; children with chronic lung disease
(CLD), also known as bronchopulmonary dysplasia
(BPD); and children with hemodynamically significant
congenital heart disease (CHD). There remains significant controversy concerning the appropriate criteria and
need for immunoprophylaxis with palivizumab for premature infants born after 32 weeks gestational age (GA).
Among premature infants, the severity of RSV infection
intuitively would be greater in those born with a GA of
32 weeks or less; however, some data indicate that the
severity of illness during hospitalization appears to be at
FIGURE
RSV is the leading cause of hospitalization of infants aged 1 year or younger
RSV hospitalization rate
Bronchitis (unspecified) hospitalization rate
Pneumonia (unspecified) hospitalization rate
Respiratory syncytial virus (RSV)
Bronchitis (unspecified)
Pneumonia (unspecified)
35
30
160,000
140,000
120,000
25
100,000
20
80,000
15
60,000
10
40,000
5
20,000
0
1997
1998
1999
2000
2001
2002
Number of hospitalizations
Hospitalization rate per 1,000 children
40
0
Source: McLaurin 2005
SUPPLEMENT / RSV
7
least as high, if not greater, in infants born 32 to 35 completed weeks of gestation (Horn 2003).
Prevention of RSV hospitalization through immunoprophylaxis is likely to have a positive economic impact beyond inpatient admissions, as it has been found that infants
hospitalized for RSV also have greater subsequent health
care utilization. In a comparison with a control group of
20,254 infants of 32 to 35 weeks GA but no RSV hospitalization during a mean follow-up of 1.66 years, a cohort of
2,415 infants hospitalized for RSV infection had not only
more hospital stays (2.96 versus 1.28; P=.001) and a longer
mean length of stay (14.71 versus 5.04 days; P<.001), but
also more outpatient visits (18.4 versus 7.54; P=.001) and
greater mortality (8.1 versus 1.6 percent; P=.001) (Sampalis 2003). In the IMpact-RSV trial (IMpact-RSV Study
Group 1998), palivizumab immunoprophylaxis reduced
hospitalization rates by 55 percent overall (10.6 versus 4.8
percent) compared with placebo, but by 80 percent in infants 32 to 35 weeks GA without CLD or CHD. Further
study and analysis is needed, however, to define the severity and utilization risks for this subset of infants, and to
establish better criteria for immunoprophylaxis.
RSV prevention
RSV immunoprophylaxis with palivizumab should be
initiated just prior to the onset of the local RSV season
and terminated at its end with intramuscular injections
administered every 30 days. American Academy of Pediatrics (AAP) guidelines (AAP 2006) recommend, in general, five monthly doses from November to March. The
AAP also states that any deviation from this recommendation requires careful consideration of the benefit and
cost. Because of the geographical and seasonal variability of RSV, I recommend that pediatricians monitor local
virology data in their respective communities along with
historical virology data to prepare for timely, appropriate administration of immunoprophylaxis. If the RSV
season should begin unexpectedly early, timely immunoprophylaxis may be difficult because of the logistical challenges involved in obtaining the necessary approvals and
supply of palivizumab. Preparation for dosing should
Michael P. Frogel, MD, is a recognized expert and researcher on
the use of palivizumab to prevent lower respiratory tract infections
due to respiratory syncytial virus (RSV) in high-risk infants and
children. He has given platform presentations and presented abstracts at the Pediatric Academic Societies and American Academy of Pediatrics yearly meetings since 1998. Frogel is an advocate for greater access to care for underprivileged patients, as well
as a leader in the development of systems to ensure the comprehensive screening of all patients and the delivery of user-friendly,
efficient compliant care. Frogel’s main areas of interest are child
advocacy, sports medicine and weight management, emergency
preparedness, and preventive pediatrics, especially immunization practices to prevent infectious disease.
8
begin in advance of the start of the RSV season in the infant’s community. For example, if the season usually starts
in November, pediatricians should begin to obtain insurance/health plan approvals during the first or second
week of October and begin to schedule appointments to
provide immunoprophylaxis during the last week of October, as it takes 48 to 72 hours to achieve protective levels with palivizumab. This approach will obviate any difficulty in receiving the necessary insurance approvals or
in scheduling patient visits before the RSV season starts.
High-risk infants will thereby receive their first injections
just prior to the start of the RSV season and achieve appropriate prophylaxis levels to prevent hospitalization.
In my practice, we screen patients year-round to identify high-risk patients who are candidates for immunoprophylaxis. We maintain an ongoing, coordinated list of
eligible patients discharged from our neonatal unit or
otherwise entering my practice. In early October, my
dedicated palivizumab nurse (a major impact on practice
manpower) studies our roster of patients and begins to
set up medical appointments and to contact insurers for
coverage approval and to check if reimbursement policy
has changed. Throughout the RSV season, we receive a report from our virology laboratory of all RSV specimens
submitted. We then track the number of tests performed
and the number of positive and negative results.
AAP guidelines
The AAP guidelines for RSV immunoprophylaxis have
evolved over the past decade. Since 1998, the AAP guidelines consistently have recommended palivizumab immunoprophylaxis for children with severe CLD who are
less than 2 years of age at the start of the RSV season (AAP
1998, 2003, 2006). For children with hemodynamically
significant CHD who are younger than 2 years at the
start of the season, the 2003 and 2006 guidelines recommend that monthly injections of palivizumab be considered during the RSV season. Current AAP guidelines
(AAP 2006) state that immunoprophylaxis should be administered usually in five monthly injections during the
RSV season and that immunoprophylaxis should be considered for premature infants who are born 32 weeks GA
or earlier and for infants 32 to 35 weeks GA with two or
more risk factors during their first RSV season (Table 1).
The AAP guidelines also mention five demonstrated
risk factors drawn from epidemiological data that may
point to an increased risk for severe RSV infection (Table
2). Other risk factors also have been identified (Table 2),
some of which are supported by evidence in the literature, but most insurers will consider only those risk factors mentioned in the AAP guidelines.
Timing of immunoprophylaxis
The question of when the first dose of palivizumab
should be administered is a major issue confronting
TABLE 1
AAP guidelines for RSV immunoprophylaxis
Presentation
Recommendation
Severe CLD* and less than 2 years of age
at start of RSV season
Palivizumab immunoprophylaxis;
patients benefit with second season of therapy
Hemodynamically significant CHD and 2 years of age
or younger at start of RSV season
Palivizumab immunoprophylaxis — 5 monthly doses; readminister after bypass surgery to maintain palivizumab levels
Immunocompromised children
No recommendations due to lack of data;
however, severe combined or acquired immunodeficiency
may benefit from immunoprophylaxis
Premature (28 weeks GA or less) and 12 months of age
Immunoprophylaxis — 5 monthly doses
of palivizumab
Premature (29–32 weeks GA) and 6 months of age
Immunoprophylaxis — 5 monthly doses
of palivizumab
Premature (32–35 weeks GA) and 6 months of age
Immunoprophylaxis if two or more risk factors are present
— 5 monthly doses of palivizumab
*Requiring treatment in the past 6 months.
CHD=chronic heart disease, CLD=chronic lung disease, GA=gestational age.
Source: AAP 2006
MCOs. In 2003, the AAP (AAP 2003) recommended
that the first dose of palivizumab be given to an infant
before discharge from the neonatal intensive care unit
(NICU); however, the 2006 guidelines (AAP 2006) do not
address this issue. In a study by Speer (2005), only 43 percent of discharges from a NICU received the first
palivizumab dose while still in the hospital; the other 57
percent received the first dose as an outpatient, and the
average number of days between discharge and the time
of that dose was 28 days (range, 0 to 122). The usual reason the first dose of palivizumab is not administered in
the hospital is financial — the hospital does not want to
absorb the cost if it is not going to be reimbursed. But deferring the first dose exposes high-risk, just-discharged
patients to RSV infection. Immunoprophylaxis takes 48
to 72 hours to reach protective levels; therefore, palivi-
zumab given at least 48 to 72 hours prior to hospital discharge should be the standard.
Even if a high-risk infant has already had an RSV infection, the AAP guidelines remind us that it is important that the infant continues to receive immunoprophylaxis, as the initial injection may not provide protection
against recurrent infection. This recommendation is
based on observations that high-risk infants may be hospitalized more than once during the same RSV season,
and more than one RSV strain may be circulating in a
community.
Treatment of RSV bronchiolitis
The aim of treatment for RSV bronchiolitis is to relieve
respiratory distress, overcome airway obstruction, enhance mucocilliary clearance, and return the child to nor-
TABLE 2
Risk factors for severe RSV infection
AAP guidelinesa
Other potential risk factors
Child care attendance
School-age siblings
Exposure to environmental air pollutants
Congenital airway abnormalities
Severe neuromuscular disease
Immune deficiencyb
Low birthweightc
Exposure to environmental/tobacco smoked,e,f
Multiple birthse
Family history of wheezing or asthmag
Minimal breast feedingg
Chronological age ≤10 weeks at RSV season onsetf,g
Crowded living conditionsg,h
Male sexc,f,h
Black racei
Low socioeconomic statusi
Sources: aAAP 2006, bMeissner 1999, cCarbonell-Estrany 2004, dFrogel 2008, eHolman 2003, fLaw 2004, gFigueras-Aloy 2004, hSimões 2003, iShay 2001
SUPPLEMENT / RSV
9
mal respiratory status. Toward these ends, the mainstays
of therapy are gentle suctioning of nasal secretions; adequate hydration (but not to the point of overhydration)
and nutrition (intravenously if necessary and if aspiration
is a concern); and oxygenation, although there is some debate about when oxygen should be provided. In routine
cases of RSV bronchiolitis, chest X-rays or complete blood
counts are of little help in guiding therapy.
Pharmacologic options that have been studied as treatments for RSV bronchiolitis include bronchodilators,
corticosteroids, antiviral agents, and leukotriene receptor antagonists. The vast majority of patients with RSV
bronchiolitis should not receive bronchodilators, as they
have not been shown to reduce the rate of hospitalization,
and they provide only modest short-term clinical benefit in patients with mild or moderate bronchiolitis (Kellner 1996). However, there may be a subpopulation of patients with reactive airway disease who will respond to a
bronchodilator. Nebulized racemic epinephrine or albuterol are often used in the inpatient hospital or emergency room. For outpatients, albuterol would be preferred, because it produces less of a rebound effect than
racemic epinephrine and is safer to use at home. Therefore, if there is a consideration of discharge from the ER
or physician’s office, albuterol should be tried. Bronchodilators should be continued only if there is an objective response to therapy.
Systemic corticosteroids may provide minimal reductions in the length of stay in infants hospitalized with
bronchiolitis (Garrison 2000); however, there is not sufficient evidence to support their use. Furthermore, data
on potential harm are lacking. AAP guidelines (AAP
2006) state that corticosteroids are not effective and are
not indicated in hospitalized infants with RSV bronchiolitis. Likewise, no data support the use of inhaled corticosteroids in RSV bronchiolitis (Viswanathan 2003).
Use of the antiviral agent ribavirin generally is not
recommended because it is difficult to use, has a high cost,
and confers potential risks to caregivers and marginal
benefits. In the Pediatric Investigators Collaborative Network on Infections in Canada study (Law 1997), there was
no statistically significant association with any outcome
measure in ribavirin-treated ventilated subsets, regardless
of risk group. In highly selected situations, AAP (2006)
states that “A decision about ribavirin administration
should be made on the basis of the particular clinical circumstances and experience of the physician.”
The rationale for using the leukotriene receptor antagonist montelukast is that leukotriene release may contribute to the development of reactive airway disease
after RSV bronchiolitis. A pilot study (Bisgaard 2003)
suggested that montelukast may be efficacious in treating recurrent respiratory symptoms in children postRSV bronchiolitis, but a larger study (Bisgaard 2008)
found that montelukast did not improve respiratory
10
Keys to successful palivizumab
immunoprophylaxis
• Screen all patients to determine high-risk infants
that require immunoprophylaxis
• Immunize with palivizumab before hospital
discharge; provide parent education
• Secure approval of required doses from insurers/
health plans before onset of the local RSV season
• Give subsequent doses monthly at home (intervals
of 30 days from last dose)
• Track all patients for compliance
• Track patient outcomes regarding hospitalizations
and any adverse events
Source: Based on author recommendations
symptoms in this population. Because of insufficient
data, this treatment is not recommended.
There is no indication for antibiotics in the treatment
of RSV bronchiolitis because it is a viral disease; however,
some patients develop bacterial pneumonia secondary to
the RSV infection. If a patient has been doing well 3 or
4 days into the course of bronchiolitis but suddenly develops a high fever and more tachypnea, a secondary
bacterial infection should be suspected. Otitis media can
be treated with antibiotics (AAP 2006). In general, there
is low risk for serious bacterial infections, and if present
in young infants, they are usually from the urinary tract.
Improving compliance
The key to optimizing protection against serious RSV
infections in high-risk patients is compliance. In a study
of 10,390 infants receiving palivizumab (Berger 2003),
noncompliant patients had a 2.2-fold increased risk of
hospitalization (1.4 versus 3.1 percent; P<.001). Compliance was defined as having, on average, 35 or fewer days
between palivizumab doses. A strategy for improving
compliance and outcomes through home-based delivery
of palivizumab injections has been recently reported
(Hand 2003, Golombek 2004). In a study of 236 infants
(Hand 2003), home care was linked to a 20 percent increase in compliance rates, fewer hospitalizations, and
fewer unscheduled medical visits. In a study of 1,446 infants (Golombek 2004), periodic nursing visits to a
home, compared with a pediatrician’s office, resulted in
greater completion of recommended doses (98 versus 89
percent; P<.001) and a lower rate of hospitalizations
(0.93 versus 3.57 percent; P<.001).
At Schneider Children’s Hospital (SCH), we have had
direct experience with home-based delivery of palivizumab immunoprophylaxis. Through an independent 5year study (Frogel 2004) conducted between 1998 and
2003, we have demonstrated that the coordination of
efforts between a NICU and a pediatric practice using
home-based delivery of palivizumab can be a highly
successful strategy for ensuring that immunoprophylaxis is provided to high-risk infants. SCH NICU gave
our general pediatric practice a discharge summary and
indications for palivizumab for all patients who would
receive follow-up care in our practice. We then entered
these patients into a database and tracked them from the
beginning to the end of the RSV season. We also notified
the insurance providers and the parents of the children
who required immunoprophylaxis. We developed a
screening tool for use with all other children coming to
our practice, and we dedicated a nurse and a physician
to track all the patients. We assigned office staff to resolve
insurance and health care provider issues. Working with
our home pharmacy provider, we started to obtain palivizumab 2 or 3 weeks before the anticipated start of the
RSV season. We also worked closely with home care
companies. Because MCOs were concerned about anaphylaxis, an anaphylaxis protocol for the home care
nurses was put in place whereby nurses were supplied
with epinephrine and a procedure to follow if a child developed anaphylaxis. As severe reactions with palivizumab are rare, we have had no cases of anaphylaxis. I
would recommend that an anaphylaxis protocol be part
of any home care program for palivizumab immunoprophylaxis.
During 5 RSV seasons, 401 patients received prophylaxis. Their distribution by GA was: Less than 29 weeks
(36 percent), 29–32 weeks (29 percent), 32–35 weeks
(25 percent), and greater than 35 weeks (9 percent). One
third of this population had CLD. Because of RSV activity in our region, tracked locally, full protection required
a series of five and sometimes up to seven palivizumab
injections for each infant born at the start of the season,
or less, depending on their date of birth within the season. Infants who had been admitted to the NICU received a first injection of palivizumab in the hospital.
During five consecutive RSV seasons, the average number of injections per patient increased each year. Over the
course of five seasons, there were only eight hospital admissions for RSV lower respiratory infection in the 395
patients available for follow-up. The hospitalization rate
of 2 percent was well below the expected rate of 10.6 percent.
We believe this program, with a greater than 90 percent compliance rate in terms of number of injections
administered in seasons 2 to 5 and with a significant
numbers of patients receiving home care, establishes a
workable, coordinated approach for palivizumab immunoprophylaxis that can be duplicated by other pediatric practices.
Real-world experience
A recent analysis of a nationwide palivizumab registry
showed that palivizumab immunoprophylaxis is associ-
ated with reduced hospitalization rates (Frogel 2008).
The registry enrolled 19,548 patients who received at
least one dose of palivizumab during four RSV seasons
at 256 pediatric sites in 41 states and the District of Columbia. Doses were administered at clinics, physician
offices, or at home. Subjects receiving doses in more
than one season were counted as separate enrollments.
Across all four seasons, 40 percent of patients were
born at a GA less than 32 weeks, 48 percent between 32
and 35 weeks, and 12 percent after 35 weeks gestation. In
addition to prematurity, common risk factors among
the patients in the registry included childcare attendance,
CLD, and CHD. Follow-up information was available for
19,474 patients. Over all four seasons, the confirmed
RSV hospitalization rate was 1.3 percent. Higher hospitalization rates were associated with male gender, birth
before 32 weeks’ gestation, a history of CLD or CHD,
congenital airway abnormalities or neuromuscular disease, and the presence of two or more children in the
household. In the fourth season, CHD was the most
common reason listed for palivizumab immunoprophylaxis in children whose GA exceeded 35 weeks.
In terms of timely administration — receipt of a dose
within 35 days of the previous one — and the number
of doses administered, the compliance rate ranged from
65 to 69 percent, and 59 percent of patients were compliant with palivizumab immunoprophylaxis by both
measures. Patients in the mixed group (office/home)
had lower compliance than either group alone. In comparison with clinic- or office-based administration of
palivizumab, home care improved compliance by both
measures (number of doses, 88 versus 81 percent;
P<.0001); timely administration, 76 versus 69 percent;
P<.0001). The home care-only group admission rate was
0.4 percent versus 1.2 percent for the clinic office-only
group.
Summary
Pharmacologic options in the treatment of RSV infection have no or minimal effectiveness. Therefore, for infants at high risk of RSV infection, proper hand hygiene,
limiting exposure to infection, and immunoprophylaxis
with palivizumab is paramount. The first injection of
palivizumab must be given prior to the start of the local
RSV season and subsequent injections should be administered every 30 days to provide protective levels
until the end of the RSV season. Pediatricians should anticipate the start of the RSV season and attend to reimbursement issues and obtain all necessary approvals well
in advance of the time when the first injections will be
given. Compliance is the key to providing protection for
high-risk infants. Compliance has a positive association
with decreasing RSV hospitalization rates; however, it is
difficult for pediatricians to achieve optimal compliance
on their own. A collaborative effort involving the hospi-
SUPPLEMENT / RSV
11
tal and NICU, pediatrician, parent, home care provider,
and insurer is necessary to achieve optimal compliance.
References
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Disclosures: Michael P. Frogel, MD, has received grant and research support and consulting fees related to palivizumab from
MedImmune, and serves on MedImmune’s speaker’s bureau.
RSV Infection in the Adult Population
JULIO A. RAMIREZ, MD, FACP
Chief, Division of Infectious Diseases, University of Louisville
Professor of Medicine, Department of Veterans Affairs Medical Center, Louisville, Ky.
Respiratory syncytial virus (RSV) is usually regarded
ure, page 14). Over the course of four winters, 2,514 resas a concern of pediatricians, whereas, in fact, RSV is a
piratory tract infections occurred among these patients.
significant and unrecognized cause of seasonal respiraUsing reverse transcriptase-polymerase chain reaction
tory tract infections (RTIs) in adults as well.
(PCR) technology, 102 RSV infections and 44 influenza
RSV may be responsible for as much as 25 percent of
infections were found among the ambulatory patients
excess wintertime mortality usually attributed
(the healthy elderly and the high-risk adults),
to influenza. For all age groups, the RSVand 142 RSV and 154 influenza infections were
associated mortality rate in the category of
found in the hospitalized patients. None of the
underlying respiratory and circulatory deaths
healthy elderly or high-risk patients with in(a group that includes pneumonia and influenza infections died. Among the healthy eldfluenza deaths but excludes the accidental
erly with an RSV infection, no deaths were
deaths that would be captured by the comrecorded, but 4 percent of the high-risk pamonly used metric of all-cause mortality) has
tients with an RSV infection died. Among the
been estimated at 4.3 per 100,000 person-years.
hospitalized patients, 8 percent of those with an
Among persons aged 65 and older, the mortalRSV infection died, as did 7 percent of those
JULIO A.
ity rate rises to 26.5 per 100,000 person-years,
with an influenza infection. On a nationwide
RAMIREZ, MD,
and 78 percent of RSV-associated underlying
basis, this RSV mortality rate was estimated to
FACP
respiratory and circulatory deaths occur in this
translate into 14,000 deaths annually. The augroup (Thompson 2003).
thors also estimated that RSV would account for about
One of the best studies showing the effects of RSV on
180,000 hospital admissions each year at a cost exceedmorbidity and mortality in adults in the United States aping $1 billion.
peared in the New England Journal of Medicine (Falsey
Clinical manifestation of RSV
2005). The study followed 680 healthy elderly patients
and 540 high-risk adults1, and 1,388 patients hospitalized
Clinical manifestation of RSV will vary with the paduring the winter with cardiopulmonary illnesses (Figtient’s age and immune status, and whether the infection
is primary or secondary. The depth to which the virus deJulio A. Ramirez, MD, FACP, received his medical degree and inscends into the respiratory tract may be regarded as an
indication of the degree to which a patient is immunoternal medicine training at the La Plata National University
compromised, owing to age or illness or both. At both exSchool of Medical Science, Argentina. He completed a fellowship
tremes of age, when the immune system either is undein Critical Care Medicine at the National Institute of Respiratory
veloped or decreasing, RSV can gain a foothold deep in
Diseases and Thoracic Surgery, University of Chile; a residency in
the respiratory tract.
Internal Medicine at Lincoln Medical Center, New York Medical
In an RSV infection, virus particles attach to airway
College; and a fellowship in Infectious Diseases at the University
epithelium, which leads to destruction of the epithelial
of Louisville School of Medicine, Kentucky. Ramirez is board cercells and damage to cilia, similar to the way the mucotified in internal medicine and holds subspecialty certification in
ciliary mechanism is damaged by the influenza virus. In
infectious diseases. His areas of research interest include clinical
severe influenza pneumonia or severe RSV pneumonia,
research, management of community-acquired pneumonia, and
the tissue damage is a consequence of the release of cytobasic research, diagnosis, and pathogenesis of infections due to
kines and chemokines. The virulence of the virus deatypical pathogens. Ramirez was a member of the U. S. Food and
pends upon its ability to provoke an immune response
Drug Administration advisory committee for anti-infective drugs
from 2001 to 2005. He is a member of the American Thoracic Society Committee for the development of national guidelines for
management of community-acquired pneumonia, and is on the
National Institute of Allergy and Infectious Diseases, Division of
Extramural Activities, Scientific Review Board.
1
Patients aged 21 years or older with physician-diagnosed heart
failure [New York Heart Association class II or higher] or chronic
pulmonary disease severe enough to restrict activities or require
the use of long-term medication.
SUPPLEMENT / RSV
13
cal response is monitored. One strategy for reducing the inappropriate use
FIGURE
of antibiotics while meeting patients’
Effects of RSV infection in elderly and high-risk patients*
expectations is to give patients a prescription for antibiotics but instruct
Epidemiology
them not to fill it for 3 to 5 days, depending on the course the disease fol680
lows. This strategy would not be adAmbulatory
visable for children, however, because
elderly
Four
persistent rhinitis often lasts for weeks
patients
RSV: 102
winters
in children with viral illness who lack
540
Flu: 44
bacterial sinusitis.
high-risk
2,514
RSV in the lower respiratory tract.
adults
RTIs
In the lower respiratory tract, acute
Hospitalized
1,388
bronchitis is one of the few infectious
RSV
hospitalized
diseases in otherwise healthy adults
RSV: 142
flu
patients
that always has a viral etiology, includFlu: 154
ing RSV. Acute bronchitis thus represents another RTI associated with the
inappropriate use of antibiotics. In
*Based on a study of healthy elderly patients and high-risk adults with physicianadults with acute bronchitis who
diagnosed heart failure or chronic pulmonary disease, and hospitalized patients with
cardiopulmonary illnesses.
cough for 2 or 3 weeks, atypical
RTIs=respiratory tract infections.
pathogens such as Myco plasma or
Source: Adapted from Falsey 2005
Chlamydia should be suspected, in
which case the patient would be a candidate for an antibiotic, such as a macrolide.
that unleashes a cytokine storm in the respiratory tract.
RSV also is an important cause of viral pneumonia in
RSV in the upper respiratory tract. Except for the
adults. Until recently, S. pneumoniae, H. influenza,
nasopharynx, the respiratory tract is sterile. The normal
Moraxella, and atypical pathogens were the pathogens
respiratory flora in the nasopharynx constitute an imporidentified in community-acquired pneumonia series,
tant defense mechanisms against infection. Viral rhinibut now influenza and RSV are recognized as the two pritis — the common cold — is the most common upper
mary viruses that cause pneumonia in adults.
respiratory infection during the winter. Viral rhinitis
often results in edema of the mucosa that predisposes the
patient to sinusitis. PCR technology also has also conRSV management
firmed that RSV is a cause of viral sinusitis (Louie 2005,
There is no evidence-based literature to define the
Ramadan 1997).
best treatment approach for RSV infections. At the UniAn issue clouding the treatment of adults with RTIs in
versity of Louisville Hospital, we use corticosteroids and
clinical practice is the inappropriate use of antibiotics,
ribavirin whenever we see cases of RSV in bone marrow
which is a primary driver for the development of multransplant patients, but these therapies are controversial.
tidrug-resistant organisms. RTIs are the leading reason
Because there is no treatment for RSV infections in
antibiotics are prescribed, but about one third of RTIs are
adults, the institution of preventive measures is paraviral and do not require antibiotics. Lacking diagnostic
mount, especially in hospitals and nursing homes where
tests to determine whether an RTI is viral or bacterial, primany immunocompromised patients live. The simple exmary care physicians sometimes prescribe antibiotics
pedient of hand washing is the key to breaking the chain
just in case the infection is bacterial. In the outpatient setof transmission. When RSV is circulating, it also may be
ting, the common cold and viral sinusitis are primary inhelpful to minimize contact between children and padications for inappropriate use of antibiotics. The probtients who are hospitalized or at high risk.
lem confronting the clinician is how to know whether
maxillary sinusitis is due to a virus or a bacterial pathogen
Summary
such as S. pneumoniae. Physicians should consider that
RSV is a significant and unrecognized cause of seaif the infection is viral, the patient will start to improve
sonal RTIs in adults, accounting for as much as 25 perin 3 to 5 days, but if a viral infection is superimposed with
cent of excess wintertime mortality usually attributed to
a bacterial infection, in 3 to 5 days the patient’s condition
influenza. Nearly 80 percent of RSV-associated underlywill worsen. If this is true, sinusitis therapy can be withing respiratory and circulatory deaths occur among the
held during the first 3 to 5 days while the patient’s clinielderly, and RSV is estimated to account for about
14
180,000 hospital admissions each year at a cost exceeding $1 billion. RSV also is recognized as an important
cause of viral pneumonia in adults.
Preventive measures, such as hand washing, are paramount, especially in hospitals and nursing homes where
many immunocompromised patients reside. When RSV
is circulating, it is advisable to minimize contact between
high-risk patients and children.
References
Falsey AR, Hennessey PA, Formica MA, et al. Respiratory syncytial virus infection in elderly and high-risk adults. N Engl J
Med. 2005;352:1749–1759.
Louie JK, Hacker JK, Gonzales R, et al. Characterization of viral
agents causing acute respiratory infection in a San Francisco University Medical Center Clinic during the influenza
season. Clin Infect Dis. 2005;41:822–828.
Ramadan HH, Farr RW, Wetmore SJ. Adenovirus and respiratory syncytial virus in chronic sinusitis using polymerase
chain reaction. Laryngoscope. 1997;107:923–925.
Thompson WW, Shay DK, Weintraub E, et al. Mortality associated with influenza and respiratory syncytial virus in the
United States. JAMA. 2003; 289:179–186.
Disclosure: Julio A. Ramirez, MD, FACP, has received grant and research support from Pfizer, Cubist Pharmaceuticals, Merck & Co.,
and Wyeth Pharmaceuticals. He is on the speaker’s bureau for
Pfizer, Cubist Pharmaceuticals, Merck & Co., Ortho-McNeil, and
Schering-Plough. He reports no real or apparent conflicts of interest with respect to proprietary products mentioned in this article.
Health Plan Medical Director:
Considerations for Prevention and
Management of RSV Disease
ALBERT TZEEL, MD, MHSA
Market Medical Officer, Great Lakes Region
Humana Wisconsin, Waukesha, Wis.
Health plans play an important role in the managetechnology investment in Humana’s history. CareHub is
ment of respiratory syncytial virus (RSV) disease. Joseph
a collaborative guidance model that engages both plan
Juran, the great pioneer in quality control who passed
members and their health care providers by leveraging
away last March, always talked about the cost of poor
technology to share information among members, physiquality in manufacturing, and said that the cost
cians, and Humana’s internal nurses, who work
of prevention is less than the cost of inspection
with our disease management vendors to imand less than the cost of internal and external
prove medical outcomes. CareHub identifies
failure. Certainly the cost of preventing a disease
pediatric members by mining claims received.
is going to be less than the cost of the disease itIt does not identify adult members, because
self. Humana’s intent is to make sure that all our
there currently is no indication for the use of
members who are candidates for RSV immunoRSV immunoprophylaxis in adults.
prophylaxis do, in fact, receive it.
The heart of CareHub is an evidence-based
At Humana, RSV management is guided by
rules engine. This tool applies accepted clinical
the three I’s: Integration of data, Identification
guidelines to an algorithm that helps us idenALBERT TZEEL,
of individuals who should receive immunoprotify specific candidates for clinical engagement.
MD, MHSA
phylaxis, and Interaction with both plan memBy mining members’ clinical profiles and anabers and physicians. Successful outreach begins with
lyzing their individual data, we can identify and evalucandidate identification. To that end, we continuously
ate potential candidates for appropriate interventions
mine our patient/physician database, which contains
and then route those candidates to those interventions.
about 4 terabytes of data (by comparison, the Library of
CareHub also enables us to conduct personalized interCongress’s data warehouse contains about 20 terabytes).
active communication campaigns via multiple channels.
These data are fed into CareHub, the largest information
Creating a clinical profile
Humana is a 47-year-old publicly traded health and supplemental benefits company serving 11.5 million members in about 20
key markets nationwide.
The clinical profile generated with CareHub provides
a unique view of every plan member. The profile incorporates data from medical claims (diagnoses, using ICD-
SUPPLEMENT / RSV
15
9 codes; types of services; and procedures) and pharmacy
claims (NDC codes; medication classes; and J codes for
office-administered medications). A clinical profile,
which, for example, includes a diagnosis of prematurity
in a child, would denote that child as a potential candidate for RSV immunoprophylaxis. These claims also can
be used in predictive modeling. Centralizing and integrating all the available data for each of our members
greatly increases our ability to target outreach and communications.
Gathering additional data from other sources helps us
to improve the sensitivity and specificity of our database,
enabling us to identify (and predict) the cohort at greatest need for obtaining case management due to a risk of
RSV infection; therefore, the clinical profile also incorporates registry data and self-generated information.
Registry data useful in RSV management are available by
diagnosis (e.g., prematurity or heart murmur), age cohort (e.g., children and elderly [if it were to become applicable]), and history (e.g., employer demographics).
Self-generated information comes from the patient’s
health risk assessment, which might reveal helpful information about smoking in the household or daycare
arrangements; the patient’s medical history, which would
incorporate information from a previous carrier; and external vendors. In summary, the clinical profile provides
myriad ways to identify those children most at RSV risk
who would benefit from case management.
Engaging patients and helping physicians
A substantial percentage of our members live in the
southern United States (Florida, Louisiana, Texas), so
we know that the annual RSV season in those geographical areas extends beyond the five months of November
through March. We have developed several “rules of engagement” for managing RSV risk, all of which depend
on access to the patient’s database. First, the patient’s
parents (member) must be continually provided with
timely, accurate information about palivizumab
(Synagis) immunoprophylaxis, but the method of contact must be one with which the member is most comfortable, whether it be by regular mail, secured e-mail, or
telephone. Second, external partners (e.g., palivizumab
vendor) must be aware of and willing to accommodate
the member’s delivery preferences (home or physician’s
office). Third, physicians must compile lists for all their
patients who may require palivizumab (their list may be
identical to ours) and make preparations to administer
the medication. We try to complement physicians’ efforts
by sending them visual aids, such as stickers for charts,
and notifying them when palivizumab is sent to their office or the patient’s home. On behalf of the physician, we
send e-mails and other reminders to the parent to make
an appointment (e.g. telephone calls utilizing voice application technology) for administration of the drug.
16
Immunoprophylaxis guidelines
Although the RSV season in many locales is limited in
duration, at Humana, preparing for the RSV season is a
year-round event. Identification of patients requiring
immunoprophylaxis is an ongoing process, and contacts
have to be made prior to the RSV season.
Because Humana relies on evidence-based medicine,
we stay consistent with the recommendations of the
American Academy of Pediatrics (AAP) for palivizumab
immunoprophylaxis. The AAP recommends that palivizumab immunoprophylaxis be considered for infants
born between 32 and 35 weeks gestational age if two or
more of the following risk factors are present: child care
attendance, school-aged siblings, exposure to environmental air pollutants, congenital abnormalities of the airways, and severe neuromuscular disease (AAP 2006).
We are amenable to speaking with physicians to address
eligibility criteria. We review all of our coverage issues on
a regular basis, but if important new information about
RSV should become available between regularly scheduled reviews, we will take that information to our Technology Assessment Forum for a possible update of our
coverage policy.
Continuous quality improvement
Humana embraces continuous quality improvement
(CQI) for its RSV risk management programs. The first
step in the CQI process is to define what we expect to see
and then to measure it — were the right candidates receiving RSV immunoprophylaxis? Unfortunately, analysis of our data suggests that about 20 percent of patients
who should have received immunoprophylaxis may not
have received it, so how can we work with physicians to
improve that number? The second step is outcomes
analysis — did we achieve what we expected to achieve?
Third, was quality of care balanced with the cost of care?
Fourth, we tie outcomes analysis into claims analysis —
did we see an impact on utilization metrics (e.g., hospital admissions per thousand patients, length of stay, readmissions)? The final step is to ask how can we optimize
our services for this population.
Summary
At Humana, our intent is to provide RSV immunoprophylaxis to all our members who need it quickly and
efficiently. Humana’s CareHub is a collaborative guidance
model that fully engages our members and their health
care providers, and allows us to leverage technology to
develop a comprehensive clinical profile for each member and to share information.
This clinical profile provides many ways in which we
can identify those children who are at high risk of severe
RSV infection, allowing us to implement RSV treatment
and management quickly and effectively before the RSV
season begins.
References
Disclosure: Albert Tzeel, MD, MHSA, has no real or apparent conflicts of interest with respect to companies, organizations, or proprietary products mentioned in this article.
Health Plan Pharmacy Director:
Considerations for Treatment and
Management of RSV Disease
DOUGLAS S. BURGOYNE, PHARMD, RPH
President, Scrip World, Salt Lake City
Along with human growth hormone and factor VIII,
palivizumab (Synagis), an approved humanized monoclonal antibody to prevent respiratory syncytial virus
(RSV) infection, was among the first drugs to be managed by health plans as a specialty drug. Specialty drugs
are the high-cost biologics and injectables that often can
blur the line between a medical benefit and a
pharmacy benefit. Because of their high cost,
health plan pharmacy directors want to be certain that specialty drugs are used at the right
time by the right population.
I recommend that physicians notify payers of the number of patients for whom they expect to provide palivizumab immunoprophylaxis and precertify the PAs for
those patients well before the anticipated start of the
season. This practice will allow both the MCO and the
physicians to be prepared for the oncoming RSV season.
The Centers for Disease Control and Prevention (CDC) defines the onset of the RSV season
as the first of two consecutive weeks in which
the median percentage of positive tests for RSV
antigen is 10 percent or greater (CDC 2007). In
some locales in Utah, we use a threshold of five
confirmed cases within seven consecutive days
Preparing for the RSV season
The RSV season usually begins in November
to determine season onset. However, even if
and extends through March, although there is
local historical data show that the RSV season
DOUGLAS S.
great geographical variability (AAP 2006). For
usually does not begin until December, and
BURGOYNE,
a health plan pharmacy director, the challenge
even if the threshold for season onset has not
PHARMD, RPH
is to budget for the inevitability of the RSV seabeen reached by then, some payers have agreed
with physicians that immunoprophylaxis should be inison on the basis of historical data. We at Scrip World rigtiated in November. Initiating therapy in November,
orously review prior authorization (PA) requests, espeeven without meeting the threshold criteria, recognizes
cially at the beginning of an RSV season, to allow for the
an agreement between the payer and the physician that
very real possibility that the season may last longer than
immunoprophylaxis will occur eventually, and that it is
usual. If we fail to keep palivizumab utilization within
better to set a definite start date for reimbursement rather
budget during the first RSV season, we will be even more
than to wait until physicians are inundated with cold and
constrained during the following season. For example, if
flu season patients, not to mention the increased risk of
historical data for the previous 5 years show that the
exposure to RSV associated with the holidays. PhysiRSV season in a given geographical area begins Nov. 15,
cians need time to prepare and to schedule and effectively
deliver RSV immunoprophylaxis to their patients and not
Douglas S. Burgoyne, PharmD, RPh, is president of Scrip World,
expose their patients unnecessarily to RSV infection.
a pharmacy benefit management company that specializes in assisting midsize self-funded employers control their pharmacy
expense. Burgoyne previously was manager of pharmacy services
for IHC Health Plans. He received both his bachelor’s and doctor of pharmacy degrees from Midwestern University, Chicago.
Burgoyne has served on the Academy of Managed Care Pharmacy
legislative, membership, and program planning and development committees.
Need for RSV guidelines
When an infant is in a neonatal intensive care unit
(NICU), it is critical for the hospital to work with the
payer to make certain that the PA for immunoprophylaxis is received before the infant is discharged. A difficult situation for an MCO arises when an infant has re-
SUPPLEMENT / RSV
17
ceived its first dose of palivizumab in the NICU, but is a
borderline candidate for immunoprophylaxis, such as an
infant born at a gestational age of 34 weeks who is relatively healthy but has only one risk factor for serious
RSV infection. If we were to evaluate this case independently, we probably would deny coverage, yet the NICU
has initiated treatment. At this point, it becomes difficult
to deny further immunoprophylaxis because of the parents’ and the physician’s expectations. Establishing regional guidelines for RSV immunoprophylaxis prior to
the onset of an RSV season and working collaboratively
with NICUs to make them aware of reimbursement policies might help eliminate this kind of conflict.
Among general practitioners, there seems to be some
confusion about palivizumab. Some physicians equate it
with a standard vaccine that requires only one or two injections. They seem unaware that palivizumab immunoprophylaxis usually involves a total of five or six injections, administered monthly starting prior to the onset
of the RSV season and continuing for its duration. In
terms of cost, the most expensive patient is the one who
receives only one or two doses and, thus, fails to receive
the long-term benefit of the drug. Sporadic administration of palivizumab is ineffective — an initial dose in November followed by a second one in January is suboptimal. Therefore, MCOs stress compliance. An MCO can
put PA in place and provide access to the drug, and issue
reminders and incentives to parents and physicians to get
immunoprophylaxis, but in the end, successful immunoprophylaxis depends on a collaborative relationship between the parents or caregivers and their physician.
ally marked up by some percentage that the MCO must
then absorb. To counter this practice, it is very likely that
MCOs will turn to home care more and more for palivizumab immunoprophylaxis, because it provides an opportunity for specialty pharmacy to contract for the drug
at a volume discount and bypass the physician markup.
This savings would more than offset the cost of a home
care visit (often $70 or more). Another cost-reduction
strategy is to have the pharmacy deliver the drug to the
patient’s house, which the patient would then take to the
physician’s office for administration.
Summary
RSV immunoprophylaxis presents a challenge for
MCOs. Despite its demonstrated ability to protect highrisk infants against serious RSV infection and to reduce
morbidity, immunoprophylaxis with palivizumab incurs
high costs that MCOs must grapple with every year. If
MCOs, physicians, and professional organizations can
agree on common guidelines for RSV management, then
MCOs will be able to provide affordable treatment for
those children at high risk.
References
virus. In: Pickering LK, Baker CJ, Long SS, McMillan JA, eds.
Redbook: 2006. Report of the Committee on Infectious Diseases. 27th ed. Elk Grove Village, Ill.: American Academy of
Pediatrics; 2006:560–566.
CDC (Centers for Disease Control and Prevention). Brief report:
respiratory syncytial virus activity – United States, July
2006–November 2007. MMWR Morb Mortal Wkly Rep.
2007;56:1263–1265.
Cost-savings through home care
Palivizumab presents a new challenge for specialty
pharmacy, because sometimes it is provided through
home care. When a physician administers the drug in the
office, the price at which the physician acquired it is usu-
Disclosure: Douglas S. Burgoyne, PharmD, RPh, reports having received honoraria from Eli Lilly, GlaxoSmithKline, and Abbott. He
has no real or apparent conflicts of interest with respect to proprietary products mentioned in this article.
ROUNDTABLE DISCUSSION
RSV Issues and Solutions
RETURN ON INVESTMENT
MICHAEL FROGEL, MD: The key message from Dr.
Simões’s presentation is that you can’t just look at
hospitalization as an endpoint. Managed care entities
need to realize there is an association between RSV infections and recurrent wheezing later in life, so there
may be more downstream costs if RSV immunoprophylaxis is not provided. That’s a key issue that has
not been addressed well.
STEVEN PESKIN, MD, MBA: For payers, what makes the
kind of information Dr. Simões provided valuable?
18
ALBERT TZEEL, MD, MHSA: There are two ways to look
at it. I agree with what Eric [Simões] is saying in terms
of the predictive value of a tool like the one he described. That is very helpful, because cost ultimately
is where the rubber meets the road. Philosophically, I
agree with the idea of looking further down the road
in terms of the potential decrease in the risk of asthma.
Given the amount of turnover in managed care, however, we are reduced to arguing in favor of paying for
a treatment now rather than for one that will provide
a return for some other MCO later.
FROGEL: If there are a limited number of insurance
FROGEL: Children are the reservoir of infection. Uni-
companies and a limited number of patients, and they
are all flipping back and forth, it doesn’t matter. You’ll
benefit if they provide immunoprophylaxis, and
they’ll benefit if you provide it.
TZEEL: We’ve bought into that argument with cardiovascular disease and asthma in adults. The difference
between those two areas and RSV immunoprophylaxis
is cost. You can’t say that you are going to spend
$20,000 and not have any return until 4 or 5 years from
now. You can spend $200 a month on cardiac medications and inhalers and nearly everyone agrees it’s
worth the cost. But when a drug costs well over $1,000
per month, and there is still some controversy about
appropriate populations, it’s too big a financial risk.
FROGEL: I would argue that with adults you spend billions of dollars on some procedures that aren’t proven
to be effective. Expenditures for children versus adults
are horrendously disproportionate. A lot of the treatments provided for adults may not be evidence-based
and may lack good outcomes. Yes, palivizumab is costly,
but there is nothing as safe and as effective as it is.
TZEEL: There are other issues to take into account. We
analyzed our national data, using the current criteria
for utilization of immunoprophylaxis. We found that,
especially in the 32- to 35-week gestational age population, we questioned about 40 percent of the requests
on the basis of whether the children met the criteria,
but their medication was authorized nevertheless.
Our bigger concern is that we believe that about 20
percent of children who should be getting palivizumab
immunoprophylaxis are not receiving it.
versal influenza vaccination for children could decrease the burden of influenza in the adult population, because the kids are the ones who spread it like
wildfire.
PESKIN: It would seem that education about RSV prevention is important, because RSV appears to present
a more significant burden in the adult and senior populations than has been generally thought.
DISEASE TRANSMISSION
FROGEL: In the prevention of viral infections, hand
washing and sterile technique are always important.
When you’re talking about hospital-acquired infections and nursing homes and high-risk patients, then
hand washing, hand washing, hand washing is the
key element to preventing nosocomial infection. Another important measure is to prevent the transmission of the virus to high-risk adults and to not allow
children to visit grandpa who is ill and laying in a bed
at home. We also recommend keeping high-risk kids
away from day care during the RSV season, and to do
the same thing with the elderly — keep them away
from exposure to RSV.
TZEEL: From a managed care perspective, we have done
a lot of outreach to our members reminding them
about simple measures like the ones you have mentioned.
JULIO A. RAMIREZ, MD: The general public doesn’t recognize that most of our immunocompromised patients are at home — the grandfather with cardiovascular disease or the newborn.
COORDINATION WITH NICU
PESKIN: Doug, are you saying that a conundrum for an
MCO is created when palivizumab immunoprophylaxis is initiated in the neonatal intensive care unit
[NICU] for a child who would not have met the
MCO’s criteria for palivizumab?
DOUGLAS S. BURGOYNE, PHARMD, RPH: Correct.
ERIC A.F. SIMÕES, MD: I’ve seen that, and when that happens, what do you do?
BURGOYNE: It depends. We often have to explain to the
NICU that although the patient doesn’t fit our guidelines, we will cover the cost of the drug because the
NICU has initiated treatment, and the family and their
physician are now expecting to receive it. But this can
create an antagonistic relationship between the hospital and the payer.
TZEEL: You don’t want to strain the relationship with the
hospital, especially if there is only one NICU in the
area.
FROGEL: Part of the problem is that the MCO isn’t providing the product for the hospital, so there is no
interaction between them. You need to tell the NICUs
that you want to work collaboratively with them and
possibly save them some money.
BURGOYNE: Absolutely. I’m all for interaction and collaboration.
TZEEL: It depends on contracting and how the NICU gets
paid.
FROGEL: This is something that has fallen through the
cracks. Whether it’s the payer or the hospital, this issue
needs to be resolved. It’s not as though the hospital
should just pay out of pocket for a drug, but hospitals
are being remiss if they do not renegotiate their contracts and include palivizumab for these patients. Contracts should set up prior-to-discharge administration of palivizumab.
SIMÕES: Our hospital did build it into its contracts with
the health plans. The problem with providing
palivizumab on the day of discharge is that palivizumab levels don’t go up for 48 hours.
FROGEL: What Dr. Simões and I are saying is that the
child who is indicated to receive palivizumab should
not leave the NICU without administration at least 48
to 72 hours before discharge.
SUPPLEMENT / RSV
19
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activity been met?
1. Explain the epidemiology, burden of
disease, and seasonal and regional
variability of RSV.
Yes No
2. Discuss the economic impact of RSV
on the health care system.
Yes
No
3. Explain which populations are at high
risk of RSV infection and why.
Yes
No
4. Discuss current and new prophylactic
options for managing RSV.
Yes
No
5. Establish educational initiatives to raise
Allow 6–8 weeks for processing.
This activity is sponsored by The
Chatham Institute and is provided at
no cost to the participant through an
educational grant from MedImmune.
the awareness of parents and health
care professionals about the prevention
and treatment of RSV. Yes No
6. Assess best practices in a managed care
T8M16-MG
20
___________________________________
D.
Fax ( _____ ) _____________________
Physicians — This activity is
designated for a maximum of 1.50 AMA
PRA Category 1 Credit(s).™
If no, please explain: __________________
C.
Daytime telephone (____) __________
E-mail __________________________
Was this publication fair, balanced, and
free of commercial bias?
Yes No
setting for managing RSV, so as to improve outcomes.
Yes No
Did this educational activity meet
my needs, contribute to my personal effectiveness, and improve my
ability to:
Treat/manage patients?
5
4
3
2
1
N/A
Communicate with patients?
5
4
3
2
1
N/A
Manage my medical practice?
5
4
3
2
1
N/A
Other ______________________________
____________________________________
5
4
3
2
1
N/A
Effectiveness of this method
of presentation:
Excellent
Very
good
Good
Fair
Poor
5
4
3
2
1
What other topics would you like to see
addressed? ________________________
___________________________________
___________________________________
___________________________________
Comments:_________________________
___________________________________
___________________________________
CONTINUING EDUCATION POST-TEST
Please tear out the assessment/evaluation form on page 20. On the answer sheet, place an X through the box of the
letter corresponding to the correct response for each question. There is only ONE correct answer to each question.
1. In the United States, how many infants are hospitalized each year because of severe RSV disease?
a. 150,000.
b. 50,000
c. 126,000.
d. 74,000.
2. In the United States, the RSV season always begins in November and ends in March of each
year.
a. True.
b. False.
3. Which of the following is not a risk factor for
severe RSV disease in infants:
a. A gestational age (GA) of 28 weeks or less.
b. Household crowding.
c. School-age siblings.
d. Malnutrition.
4. A long-term outcome of RSV in infancy may be:
a. Chronic lung disease.
b. Physician-diagnosed asthma.
c. Allergies.
5. Palivizumab is an FDA-approved _____ that is
administered _____ to prevent severe RSV
disease in _____ infants.
a. Monoclonal antibody, intramuscularly, high-risk.
b. Monoclonal antibody, orally, all.
c. Polyclonal globulin, intravenously, high-risk.
6. Current AAP guidelines recommend that at the
start of an RSV season, palivizumab immunoprophylaxis should be considered for children
less than 2 years of age with severe chronic lung
disease or congenital heart disease, and also for:
a. Infants born 32 weeks GA or less.
b. All infants younger than 1 year.
c. All infants who are not breastfeeding.
7. According to Frogel, for optimal value, RSV immunoprophylaxis should be given _____ the RSV
season begins, terminated _____ after the season, with intramuscular injections of
palivizumab administered _____ :
a. 2 months before; 1 month after; every 45 days.
b. 1 month before; 1 month after; every 30 days .
c. 1 week before; at the end of the season;
every 30 days.
8. According to Frogel, compliance with immunoprophylaxis for high-risk infants can best be
maintained by:
a. Better coordination between the neonatal intensive care unit and pediatricians and home-based
delivery of palivizumab.
b. Parent education.
c. Better tracking of high-risk infants to determine
adherence to immunoprophylaxis.
d. All of the above.
9. Among persons 65 years and older, what
percent of deaths can be attributed to RSVassociated underlying respiratory and circulatory diagnoses?
a. 65 percent.
b. 78 percent.
c. Less than 50 percent.
10. The most effective treatment for RSV infections
in both the upper and lower respiratory tract in
adults is:
a. Corticosteroid therapy.
b. Antibiotic therapy.
c. Good hygiene practices.
11. A primary advantage of Humana’s CareHub information technology program is its ability to:
a. Identify specific candidates for RSV case management.
b. Keep an accurate record of all medical and pharmacy claims.
c. Develop clinical guidelines for RSV immunoprophylaxis.
12. In the management of RSV, Scrip World uses
prior authorization as a way to:
a. Identify specific candidates for RSV case management.
b. Keep an accurate record of all medical and pharmacy claims.
c. Develop clinical guidelines for RSV immunoprophylaxis.
SUPPLEMENT / RSV
21

supplement

Transcription

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