Download Paediatric Review March 2006

Respiratory Syncytial Virus Prophylaxis
2010-2011
Chuck Hui MD FRCPC
Paediatric Infectious Diseases
Assistant Professor of Paediatrics
Objectives
• Review the basics of RSV
• Understand the ways to prevent and manage RSV
• Discuss the MOHLTC Ontario criteria for
palivizumab approval
• Discuss the process for obtaining palivizumab for
high risk patients
What is RSV?
• RNA paramyxovirus
– 2 strains – A and B
• Often circulate concurrently
• Humans are only source
• Almost all children infected at least once by 2 yrs of
age
• Re-infection is common
• Presents as a common URI in older children and
adults
Epidemiology
• Annual season in Canada
– November to April
• Viral shedding 3-8 days
– May be longer in young and immunosuppressed
• Incubation period 2-8 days
• Supportive care, no good treatment
Burden of RSV in Young Children
• Population based study in children < 5yrs
• ER (2000-2004); Pediatric offices (2002-2004)
• 5067 enrolled; 919(18%) RSV infections; RSVH overall
•
•
(11%)
RSV associated with: 18% ER visits
15% office visits (3X ER)
Average RSVH: 17/1000 <6 months of age
3/1000 < 5 years of age
Hall CB et al. NEJM 2009;360:588-598
Burden of RSV in Young Children
• Majority of children had no underlying medical illness
• Only risk factors identified: < 2 years of age, history of
prematurity
• Under 5 yrs of age RSV results in:
 1 of 38 visits to the ER
 1 of 13 visits to a primary care (FD) office
Hall CB et al. NEJM 2009;360:588-598
Global Burden
• Global burden of disease related to RSV in
children younger than 5 years
• Systematic review 1995-2009
– 33.8 million new episodes of RSV-associated ALRI
occurred worldwide in children younger than 5 years
– 3.4 million episodes representing severe RSVassociated ALRI necessitating hospital admission
– 66 000–199 000 children younger than 5 years died
from RSV associated ALRI in 2005
• 99% of these deaths occurring in developing countries
Lancet. 2010 May 1; 375(9725)
Asthma
• Matched cohort study of hospitallized RSV
bronchilitis patients with controls
• Follow-up at 18 years
• Results:
– 46/47 subjects and 92/93 controls assessed at
18 years of age
– Asthma/RW 39% vs 9%
– Clinical allergy 42% vs 17%
Thorax. 2010 Jun 27
Treatment
• Does not work…
–
–
–
–
–
–
Bronchodilators
Steroids
Hypertonic saline
Physiotherapy
Montelukast
Antibiotics
Cochrane Database Systematic Review. 2006
Cochrane Database of Systematic Reviews. 2004
Cochrane Database Systematic Reviews 2007
NEJM 357;4, July 26, 2007
NEJM 360;20 May 14, 2009
British Medical Journal 1966;1:83–5
How can we prevent RSV transmission?
RSV
• nosocomial outbreaks recognized 1970s
• transmission established 1981!!
–
–
–
–
Hall and Douglas, J Pediatr 1981;99:100-102
3 plausible routes: aerosol, droplet, contact
31 volunteers: cuddlers, touchers, sitters
71% of cuddlers, 40% touchers, 0% sitters developed
culture confirmed infection
RSV
• 107 virus particles per mL of nasal discharge in
children
• infectious dose - ??
• survives on inanimate
objects
for prolonged
periods of time
Goldman PIDJ 2000;19:S97-102
Risk factors for RSV
hospitalization worldwide
Exposure
• Age at start of RSV
season
• Siblings
• Crowding at home
• Day care attendance
• Day care attendance of
siblings
• Discharge between
October and December
Social Factors
• Breast feeding
Physiologic Factors
• Low birth weight
• Male sex
• Family history of wheezing
• CLD
• Neurologic problems
• Birth order >2nd
Eur J Clin Microbiol Infect Dis (2008) 27:891–899
% reduction in hospitalization
Background
Palivizumab Efficacy
100
80
80
60
55
39
47
40
20
0
Overall
BPD
<32 wks
32-35 wks
IMPACT Pediatrics 1998
Efficiencies of Sharing Vials
• Palivizumab is expensive!
– 50mg - $752.26
– 100mg - $1,504.51
• The Cost and Safety of Multidose Use of Palivizumab
Vials
– 446 vials - $37 410 savings
– One vial had bacterial contamination
– 16% cost savings
Gooding J et al. Clin Pediatr (Phila) 2008 Mar;47(2):160-3.
Wills S Arch. Dis. Child. 2006;91;717
Requests that Satisfy the Recommendations
of NACI 2003 and CPS 2009
• Infants born prematurely at ≤ 32 completed weeks
gestation and aged ≤ 6 months at the start of, or during,
the local RSV season
• Children < 24 months of age with bronchopulmonary
dysplasia (BPD)/chronic lung disease (CLD) AND who
required oxygen and/or medical therapy within the 6
months preceding the RSV season
• Children < 24 months of age with hemodynamically
significant cyanotic or acyanotic congenital heart disease
(requiring corrective surgery or on cardiac medication for
hemodynamic considerations).
Requests that Satisfy the Advice from the Ontario RSV
Prophylaxis for High-Risk Infants Advisory Group
Infants in the 33-35 Completed Weeks (33 weeks and
0 days to 35 weeks and 6 days) Gestational Age
Cohort and Aged ≤ 6 Months at the start/during
the local RSV season
• Infants who live in isolated communities
• Infants who do not live in isolated communities
– Requests for these infants (33-35 completed weeks) must include
a completed Risk Assessment Tool signed by the requesting
physician.
• Siblings in the Same Multiple Birth Set of a HighRisk Infant
• Infants with Down Syndrome/Trisomy 21
Variables in the final Logistic Regression Model
(Risk Scoring Tool- PICNIC Study)
Variable
Score
SGA (GA <10%)
[ Yes/No ]
Gender (Male/Female)
Birth Month (Nov,Dec,Jan)
Subject or Siblings in Day Care [ Yes/No ]
Family History without eczema [ Yes/No ]
>5 individuals in the home counting
the subject [ Yes/No ]
Two or more smokers in the house [Yes/No ] 10
12
11
25
17
12
Total
100
13
CONSIDERATION OF SPECIAL CLINICAL
CIRCUMSTANCE
Individual Patient Case Reviews
• Requests for high-risk infants that do not satisfy the above
approval criteria will be considered by the ministry’s
expert clinicians in RSV prophylaxis
• These requests must state the patient’s specific medical
illness, include a letter from the requesting physician
detailing the clinical rationale, AND a supporting letter
from either an infectious disease specialist or a
neonatologist or a respirologist
• Potential special requests:
– Upper airway diseases
– Immunodeficiency
– Cystic fibrosis
SUMMARY OF CHANGES FOR THE
2010-2011 RSV PROPHYLAXIS SEASON
REVISED REQUEST PROCESS:
• Enrolment requests will continue to be evaluated by the ministry.
Initial dose requests can be processed by the ministry or by Abbott
Canada (Abbott). However all subsequent monthly dose/vial requests
must be faxed to Abbott for processing.
REVISED MINISTRY FORMS:
• Forms have been revised and enhanced with embedded tools to
support and facilitate the new request process
DOSE INTERVALS:
• A clinical or logistical rationale must be provided if intervals between
doses are too short – i.e. less than 21 days between the first and
second dose and less than 30 days for all subsequent doses
SEASON START:
• For eastern, central, and southern Ontario, the prophylaxis
season will start on or around November 1st
SEASON END:
• April 1st, 2011
• If requiring after April 1st, the requesting physician must
confirm to the ministry that the RSV season is continuing in
the patient’s area of residence by providing the date and
name of the health institution that was consulted
REVISED REQUEST PROCESS
• All enrolment requests must be faxed to the Ministry (416-326-1990
or 877-588-1658)
• INITIAL dose requests will be processed by the ministry if the 1st
row of the palivizumab supply request table on page 2 of the
enrolment/request form is completed and faxed at the same time as
the enrolment request
– Alternatively, the dose request can be submitted directly to Abbott by
faxing ONLY page 2 of the enrolment form or a multi-patient order
form.
• All other dose requests must be faxed to Abbott (800-513-7337) for
processing. Fax ONLY page 2 of the enrolment form or a multipatient order form for this purpose. Do not fax page 1 of the
enrolment form to Abbott – this page contains the patients personal
health information
REVISED MINISTRY FORMS
•
•
•
•
For the 2010-2011 RSV prophylaxis season, only the patient
enrolment/request form has been significantly revised.
The Risk Assessment Tool (RAT) and the multi-patient supply request forms
remain the same
Users can complete the forms online or download the forms in either PDF or
Microsoft Word format and save it to their local system for future use.
However, the forms will NOT save any information entered by a user. All recurring
information (e.g. physician information) must be re-entered when the file is reopened.
The links to the forms are available from the ministry’s program webpage:
(http://www.health.gov.on.ca//en/public/programs/drugs/funded_drug/fund_res
piratory.aspx) or from the Ontario Central Forms Repository
(http://www.forms.ssb.gov.on.ca/mbs/ssb/forms/ssbforms.nsf )
•
•
•
•
Enrolment/Request Form (form: 4645-87E)
Risk Assessment Tool (RAT) (form: 4646-87E)
Multi-Patient Palivizumab Supply Request and Dose Report (form: 4647-87E)
Multi-Patient Palivizumab Supply Request and Dose Report (Hospital Use Only)
2010-2011
2009-2010
Enrolment Form
Risk Assessment Tool
What do you do?
• Individual office/clinic, palivizumab in your clinic
–
–
–
–
Fill out enrolment form
Enrolling and follow-up physician the same
Fax 2nd page to Abbott
If have multiple patients may use the MOH or
Abbott multiple patient request form
What do you do?
• NICU/Clinical areas
– Identify patients that qualify in a log book
• Ensure that RAT is filled out when appropriate
– If the patient is to be discharged home during
the season
• Fill out enrolment form
• Obtain the first dose and provide in NICU
• Send enrolment form to RSV clinic
CHEO RSV
Prophylaxis Program
Website: www.cheo.on.ca -> Professionals -> Referring patients
to CHEO -> RSV Prophylaxis
Email: [email protected]
Telephone: 613-737-7600 x2406
Fax: 613-738-4832
C1 clinic – start date November 5, 2010
MOH forms and letter
• www.health.gov.on.ca//en/public/programs/
drugs/funded_drug/fund_respiratory.aspx
• www.forms.ssb.gov.on.ca/mbs/ssb/forms/ss
bforms.nsf
Questions?