1. Chuck Hui MD FRCPC Paediatric Infectious Diseases Assistant Professor of Paediatrics Respiratory Syncytial Virus Prophylaxis 2010-2011

2. 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

3. 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

4. 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

5. 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

6. 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

7. 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 RSV- associated 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)

8. 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

9. 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

10. How can we prevent RSV transmission?

11. 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

12. RSV 10 7 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

14. 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 >2 nd Eur J Clin Microbiol Infect Dis (2008) 27:891–899

15. Background Palivizumab Efficacy IMPACT Pediatrics 1998

16. 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

18. 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).

19. 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 High- Risk Infant Infants with Down Syndrome/Trisomy 21

20. Variables in the final Logistic Regression Model (Risk Scoring Tool- PICNIC Study) Variable Score SGA (GA <10%)[ Yes/No ]12 Gender (Male/Female)11 Birth Month (Nov,Dec,Jan)25 Subject or Siblings in Day Care [ Yes/No ]17 Family History without eczema [ Yes/No ]12 >5 individuals in the home counting the subject [ Yes/No ]13 Two or more smokers in the house [Yes/No ]10 Total100

21. 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

22. 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

23. SEASON START: For eastern, central, and southern Ontario, the prophylaxis season will start on or around November 1 st SEASON END: April 1st, 2011 If requiring after April 1 st, 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

24. 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 multi- patient order form for this purpose. Do not fax page 1 of the enrolment form to Abbott – this page contains the patients personal health information

25. 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 re- opened. 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 )http://www.health.gov.on.ca//en/public/programs/drugs/funded_drug/fund_res piratory.aspxhttp://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)

26. 2010-2011 2009-2010

28. Enrolment Form

31. Risk Assessment Tool

37. What do you do? Individual office/clinic, palivizumab in your clinic –Fill out enrolment form –Enrolling and follow-up physician the same –Fax 2 nd page to Abbott –If have multiple patients may use the MOH or Abbott multiple patient request form

38. 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

39. CHEO RSV Prophylaxis Program Website: www.cheo.on.ca -> Professionals -> Referring patients to CHEO -> RSV Prophylaxiswww.cheo.on.ca Email: rsvclinic@cheo.on.carsvclinic@cheo.on.ca Telephone: 613-737-7600 x2406 Fax: 613-738-4832 C1 clinic – start date November 5, 2010

40. MOH forms and letter www.health.gov.on.ca//en/public/programs/ drugs/funded_drug/fund_respiratory.aspxwww.health.gov.on.ca//en/public/programs/ drugs/funded_drug/fund_respiratory.aspx www.forms.ssb.gov.on.ca/mbs/ssb/forms/ss bforms.nsfwww.forms.ssb.gov.on.ca/mbs/ssb/forms/ss bforms.nsf

41. Questions?