1 / 196

Prophylaxis in countries with limited resources – can it be done? .. Should it be done?

Prophylaxis in countries with limited resources – can it be done? .. Should it be done?. Dr Manuel Carcao Paediatric Hematologist, Hospital for Sick Children; Associate Professor, University of Toronto. Thanks to (Organizers; the WFH & Bayer) for inviting me to Lebanon.

andres
Download Presentation

Prophylaxis in countries with limited resources – can it be done? .. Should it be done?

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Prophylaxis in countries with limited resources – can it be done? .. Should it be done? Dr Manuel Carcao Paediatric Hematologist, Hospital for Sick Children; Associate Professor, University of Toronto

  2. Thanks to (Organizers; the WFH & Bayer) for inviting me to Lebanon Honor to be here in your country

  3. Hemophilia A severe bleeding disorder

  4. Patients not on Prophylaxis = On demand Wed Tues Mon Tues Thurs Fri Sat Sun Mon

  5. Patients not on Prophylaxis = On demand Patient is always at high risk of bleeding Wed Tues Mon Tues Thurs Fri Sat Sun Mon <1% = highest risk of bleeding

  6. Prophylaxis Time at risk of bleeding greatly reduced Protected Protected Protected Tues Wed Mon Thurs Fri Sat Sun Mon <1% 2 days / wk = highest risk of bleeding

  7. Prophylaxis Protected Protected Protected Wed Mon Tues Thurs Fri Sat <1% Sleeping Sleeping Every 3 days = highest risk of bleeding

  8. Prophylaxis Always Protected Wed Mon Tues Thurs Fri Sat <1% Every 2 days = highest risk of bleeding

  9. Hemophilia Without Prophylaxis < 1% 1-5% >5%

  10. Hemophilia Without Prophylaxis Develop joint disease in early childhood < 1% 1-5% >5%

  11. Prophylaxis: Definitions • “Administration of factor on a regular basis to prevent bleeding and to preserve (short & long-term) health” Consensus Conference on Prophylaxis ( London, UK 2002 )

  12. Prophylaxis: Definitions • Primary Prophylaxis started at a very young age( ≤ 2 yr ) prior to development of joint disease • Secondary Prophylaxis commenced at a older age after some joint disease

  13. Prophylaxis: Definitions

  14. Goals of Prophylaxis 1) Prevent acute bleeds

  15. 2) Prevent Limb/Life threatening bleeds Ileopsoas muscle Hip bleed  AVN Intracranial

  16. 3) Prevent development of hemophilic arthropathy

  17. 4) Keep patients with hemophilia healthy and active

  18. Goals of prophylaxis • Developed countries: “Perfect joints” • Developing countries: more modest • Decrease bleeding • Improve quality of life (QoL) • Delay progression of joint disease

  19. Lessons in Prophylaxis • Prophylaxis results in better clinical outcomes • Prophylaxis should ideally start early • Patients have different prophylaxis needs • There are many burdens associated with Prophylaxis • Low and Intermediate dose Prophylaxis is an option

  20. Lessons in Prophylaxis • Prophylaxis results in better clinical outcomes • Prophylaxis should ideally start early • Patients have different prophylaxis needs • There are many burdens associated with Prophylaxis • Low and Intermediate dose Prophylaxis is an option

  21. Benefits of Prophylaxis:↓ bleeding 27 boys with severe hemophilia Median Age (yr) at start of prophylaxis = 6.2 yr HA 15 – 25 U/kg 3/wk HB 15 – 25 U/kg 2/wk 15 (90% less) 1.5 On demand On Prophylaxis Liesner et al. BJH 1996; 92:973 -8

  22. Benefits of Prophylaxis:↓ bleeding Pts with severe hemophilia 90% less 3X more Smith et al: J Pediatr 1996; 129: 424-31.

  23. OR 90% less 90% less 25-40 U/kg every other day = Full dose “Malmo” prophylaxis Manco-Johnson M.J. et al, NEJM, 2007; 357: 535-44

  24. Prophylaxis leads to better joints Prophylaxis On demand (Full dose = Malmö) Patients enrolled by age 2.5 yrs Mean Joint Physical exam score Age Manco-Johnson M.J. et al, NEJM, 2007; 357: 535-44

  25. Prophylaxis leads to better joints Prophylaxis On demand (Full dose = Malmö) Large difference in joint scores after only a few years Patients enrolled by age 2.5 yrs Mean Joint Physical exam score Age Manco-Johnson M.J. et al, NEJM, 2007; 357: 535-44

  26. Prophylaxis leads to other clinical benefits

  27. Lessons in Prophylaxis • Prophylaxis results in better clinical outcomes • Prophylaxis should ideally start early • Patients have different prophylaxis needs • There are many burdens associated with Prophylaxis • Low and Intermediate dose Prophylaxis is an option

  28. Netherlands: 76 men with severe haemophilia A were evaluated at 19 yrs of age Mean Pettersson (Xray) scores at age 19 yrs (n=16) 2 (n=34) 8 (n=26) 11.5 Worse joint disease Fisher et al (Blood, 2002)

  29. Netherlands: 76 men with severe haemophilia A were evaluated at 19 yrs of age Mean Pettersson (Xray) scores Age at starting prophylaxis at age 19 yrs < 4 yrs (n=16) 2 4-7 yrs (n=34) 8 ≥ 8 yrs (n=26) 11.5 Worse joint disease Fisher et al (Blood, 2002)

  30. Sweden: 55 boys with SHA followed for median (11 yrs) from starting prophylaxis All pts received full dose prophylaxis (Ljung, Haemophilia 2002)

  31. Sweden: 55 boys with SHA followed for median (11 yrs) from starting prophylaxis Start Prophylaxis early All pts received full dose prophylaxis (Ljung, Haemophilia 2002)

  32. Lessons in Prophylaxis • Prophylaxis results in better clinical outcomes • Prophylaxis should ideally start early • Patients have different prophylaxis needs • There are many burdens associated with Prophylaxis • Low and Intermediate dose Prophylaxis is an option

  33. Patients are different & have different bleeding predispositions Age at 1st joint bleed Frequency of bleeding Biological differences 2-3 fold Differences in PK Differences in physical activities

  34. Patients are different & have different bleeding predispositions Age at 1st joint bleed Frequency of bleeding Prophylaxis needs may be very different Biological differences 2-3 fold Differences in PK Differences in physical activities

  35. Lessons in Prophylaxis • Prophylaxis results in better clinical outcomes • Prophylaxis should ideally start early • Patients have different prophylaxis needs • There are many burdens associated with Prophylaxis • Low and Intermediate dose Prophylaxis is an option

  36. Benefits vs. “Burdens” of prophylaxis Benefits of Prophylaxis  Burdens of Prophylaxis • Venous access • Cost Many

  37. Cost Prophylaxis is expensive

  38. Costs of prophylaxis vs. on demand change over time Prophylaxis: Cost  Same costs 3 X higher Consumption of factor U / kg On demand: Cost  Age of patient in Years From A. Shapiro

  39. Cost may not rise very much low/intermediate dose prophylaxis On demand switching

  40. 84 boys/adults switched from on demand to prophylaxis (25 U/kg given 2 or 3 X / wk) 90% less 39% more Tagliaferri A et al. Haemophilia 2008; 14:945-51

  41. 84 boys/adults switched from on demand to prophylaxis (25 U/kg given 2 or 3 X / wk) Prophylaxis: Only a bit more expensive than on demand (but much more effective) 90% less 39% more Tagliaferri A et al. Haemophilia 2008; 14:945-51

  42. Lessons in Prophylaxis • Prophylaxis results in better clinical outcomes • Prophylaxis should ideally start early • Patients have different prophylaxis needs • There are many burdens associated with Prophylaxis • Low and Intermediate dose Prophylaxis is an option

  43. Experiences of low / intermediate dose prophylaxis in developing countries C. China B. Iran A. Thailand

  44. A) Thailand • 1 year Pilot study on LOW DOSE prophylaxis in 6 hemophilic boys (ages 11-16; median 12 yr) with severe/moderate hemophilia A • Prophylaxis regimen • 8-10 U/kg 2 X/wk • Plasma derived FVIII concentrate (not specified) Chuansumrit A et al., 1995. 26(2):243-6.

  45. A) Thailand: Results • Bleeds per pt per year • Hospitalization days per pt per year • Cost of prophylaxis was $7,200 US/pt/yr On demand: 11.5 On prophylaxis: 2.3 On demand: 15.8 On prophylaxis: 0 Chuansumrit A et al., 1995. 26(2):243-6.

  46. B) Iran • 6 month Retrospective review of 25 boys (0-9 yrs of age) with severe hemophilia A On INTERMEDIATE DOSE prophylaxis: (15 U/kg 3 X/wk) 11 boys (1 institution) On demand: 14 boys (2 institutions) Daliri et al. Intern J Tech Assess Health Care 2009; 25:584-7.

  47. B) Iran (90% less) 2.5 X more Daliri et al. Intern J Tech Assess Health Care 2009; 25:584-7.

  48. C) China • 34 Children (ages: 3-18) with Severe (n=13 pts) OR Moderate (n=21 pts) Hemophilia A OR B AND established joint disease • Placed on 12 wk LOW DOSE prophylaxis • Doses: • 10 U/kg 2X / wk for hemophilia A • 20 U/kg 1X / wk for hemophilia B ≈1,100 U/kg/yr R. WU et al. Hemophilia 2011.

  49. Results Severe hemophilia (n=13) Moderate hemophilia (n=21) 12 8.6 2.6 0.9 On demand Prophylaxis On demand Prophylaxis 12 wk period 12 wk period 12 wk period 12 wk period

  50. Results • Improvement in joint function Most patients • Reduced school absences On demand: 21 days lost / child On prophylaxis: 1.4 days lost / child R. WU et al. Hemophilia 2011.

More Related