1 / 28

Low Dose Prophylaxis

Low Dose Prophylaxis. Lisa N Boggio, MS, MD RUSH University Medical Center Chicago, Illinois USA. Treatment Regimens Before Blood Products. Avoidance of activity R.I.C.E . Rest, Ice Compression, Elevation Quackery Alternative medicine. 90% of persons with hemophilia were dead by age 21.

filiberto
Download Presentation

Low Dose Prophylaxis

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. Low Dose Prophylaxis Lisa N Boggio, MS, MD RUSH University Medical Center Chicago, Illinois USA

  2. Treatment RegimensBefore Blood Products • Avoidance of activity • R.I.C.E. • Rest, Ice Compression, Elevation • Quackery • Alternative medicine 90% of persons with hemophilia were dead by age 21

  3. Treatment • 1940s FFP • 1950-60s Cryoprecipitate • 1970s purified FVIII +vWF • 1980s highly purified FVIII and IX • 1990s recombinant FVIII and IX • 2000s recombinant FVIII with little or no human proteins • 2010s prolonged half life Hambleton J. Curr Opin Hematol. 2001;8:306-311.

  4. Annual age-adjusted mortality rate for deaths from bleeding 37% reduction 29% reduction Darby et al. Blood, 2007;110(3)115

  5. Mortality severe Darby et al. Blood, 2007;110(3)815

  6. Joint Disease:Scope of the Problem • Occurs in 90% of severe hemophilia • Joint bleeds per year: 15 +12 • Restriction in activity: at least 50% of patients Aledort L. J Int Med. 1994; 236: 391

  7. Development of Joint Disease • Synovial membrane vessels bleed into articular space • Iron inflammatory reaction • Synovium hyperemic and hypertrophic • Eventual cartilage/bone destruction

  8. ElbowXRAY

  9. Arthroscopy

  10. On Demand Therapy Globe DR. Haemophilia 2004. 10(Sup 1):63-70 • Does not prevent the development of hemarthrosis • In the US, Cost $130,102/yr • Prophylaxis • Better outcomes • More normal life • More cost

  11. Factor Dose Bleeds/Month No prophylaxis 5.5 4 U/kg/day 2.5 8 U/kg/day* 1.5 24 U/kg 3x/wk 1.0 32 U/kg once/wk 4.5 Prophylaxis – Early Studies Dose and interval are important * Cost equivalent: no prophylaxis Kasper. Arch Intern Med. 1970; 125: 1004.

  12. Secondary Prophylaxis for Joint Disease Conclusions: 1) Physical findings generally improve 2) X-ray: stable to progressive deterioration

  13. When to Start:Swedish Experience • Patients: n = 121; age <10; at least one infusion/week • Decreased bleeds correlated with: • shorter infusion interval (p < 0.005) • age < 3 years (p < 0.0002) • Joint disease correlated with: • age when treatment started (p = 0.0002) • dose and interval at start age not significant Astermark. Brit J Haematol. 1999;105:1109

  14. Swedish Experience All values are mean Nilsson. J Int Med. 1992; 232: 25

  15. ESPRIT Study Gringeri A . J Throm Haem. 2011. 9(4):700-710 72 patients Randomized study 24 IU/kg TIW Prophylaxis with improved quality of life Estimated cost for 7 years 200,000€ (2500€ monthly)

  16. Is Prophylaxis ‘Worth It’? Feldman BM. Haemophilia 2012. 18:680-684 • Inherited – not the person’s fault they have it • Children primarily effected • Individuals place greater weight on health gains by children than adults • Rare condition – small public impact • Prophylaxis is preventive treatment • Expensive due to need for safety

  17. Outcomes Modeling Fischer K. Blood 2013; 122: 1129-36 • Swedish model – trough >1% • 25-40 IU/kg 3x/wk or QOD • Netherlands – prevent spontaneous bleeding • 10-15 IU/kg 3x/wk or QOD • 24 year follow up • Swedish with a 66% increased annual cost • Outcomes similar QOL and Employment

  18. Comparison Fischer K. Blood 2013; 122: 1129-36

  19. Should prophy be for children and On-demand for adults? Fischer K. Haemophilia 2016; 1-8 • Compared to on-demand, prophylaxis has better outcomes • Even at lowest dose (1000 IU/kg/yror 10 IU/kg twice weekly) • Increased effectiveness up to 4500 IU/kg/yr (25 IU/kg 3-3.5 times/week) • Switch to on-demand as adults • Pristine joints at start of on-demand • 10 year increase in Petterson scores

  20. What to Do with Limited Resources? Verma SP. Haemophilia 2016; 22:342-348 • Short term pilot study from China • Indian study – randomized open label study • Children aged 1-10 • 10 IU/kg twice a week • 25 IU/kg on-demand • Xray& HJHS • 12 month follow up

  21. Study Groups

  22. Results

  23. Results

  24. Costs/Benefits • Prophylaxis 1.5 times higher than on-demand • Most of this is factor • Fewer days lost from school • 3 days prophylaxis v 25 days on -demand • No change in Petterson score

  25. Prophylaxis Advantages • Decreased bleeding • Reduced joint damage • Increase activity • Increase school attendance Disdvantages • Cost • Intravenous access

  26. 100,000 Episodic Care Prophylaxis 80,000 60,000 Cost per Year ($) 40,000 20,000 0 Medical Care Medical Care Factor Total Factor Total The Cost of Prophylaxis Smith P et al. J Pediatr. 1996;129(3):424-431

  27. What’s Reasonable? • Primary prophylaxis – start early • < 2 bleeds/joint • 1 bleed/several joints • Age < 3 years • Secondary prophylaxis – short term • 4 bleeds/joint over 6 months • Treat for 3-6 months • Preventive prophylaxis • Prior to strenuous or high risk activities or surgeries

  28. Thank you!

More Related