Hemophilia care: Current guidelines and applications of new factor concentrates

Transcription

1 Hemophilia care: Current guidelines and applications of new factor concentrates K Fischer MD PhD Van Creveldkliniek University Medical Center, Utrecht, The Netherlands

2 Guidelines identified: WFH UKHCDO 2010 Richards. BJH 2010; 149: 498 France 2009 Meurnier S. Arch de Pediatrie 2009; 16:1571 USA 2007 MASAC, nr 179; Dutch 2009 NVHB, ISBN Germany 2008 not published in journal

3 Things to consider when making treatment decisions

4 Half life increases with age for FVIII only FVIII ±8 15 hours FIX ± 20 hours Björkman S. Blood 2012;119: Björkman S. Haemophilia 2001; 16:

5 Trough levels appear most important in children Age 1-6 yrs If FVIII>1% 2 7 days/wk: Children: 40% 90% no bleeds Age yrs Adults: 20% 54% no bleeds Collins P. JTH 2008; 7: 413

6 Long(er) acting concentrates technique Factor VIII Pegylation (n=3) Fc fusion (n=1) VWD binding (n=1) Factor IX Half life X 1.5 X 3-5 Registered Prophylactic regimens used in studies Alprolix (USA, CA, Japan) Fc fusion Pegylation (n=1) Fc fusion (n=1) Albumin fusion (n=1) Eloctate (USA, CA, Japan) Fc fusion 2-1 x/week 1x/ 2-3 weeks

7 Collins et al Haemophilia 2011; 17: 2-10 Prophylaxis with longer acting concentrates Time with low levels Peak levels

8 Collins et al Haemophilia 2011; 17: 2-10 Prophylaxis with longer acting concentrates (II) Protection during sports?

9 Natural experiment of long-term low trough levels of FVIII/IX: moderate haemophilia (I) prophylaxis Den Uijl. Haemophilia 2011; 17: 849

10 Natural experiment of long-term low trough levels of FVIII/IX: moderate haemophilia (II) N=75, age 34 yrs Den Uijl. Blood Transfusion 2014; 12 Suppl 1: S330

11 Very young children do not bleed very often annual no of joint bleeds age cum no of joint bleeds Fischer et al, Acta Radiol 2002;43:528 Collins P. JTH 2008; 7: 413

12 Powell J et al BJH 2014;epub Sept 11 Experience with long acting FIX 25/28 patients used FIX prophylaxis 2-4 times weekly On study: 50 IU/kg 2x/wk, or 100 IU/kg 1x/wk, or 50 IU/kg1x/wk Sports not mentioned

13 Considerations for prophylactic treatment Bleeding is dependent on FVIII levels, especially in children FVIII half life increases with age from ±8 to ±15 hours More frequent infusions allow for maintanance of trough levels with lower dosages FVIII levels of 1-5% protect against bleeding in most patients Some patients on long-acting FIX can get by with infusions every 2-3 weeks

14 Recommendations and new concentrates: starting prophylaxis Timing: by 2nd joint bleed/significant soft tissue bleed. (UK) Or max 2 bleeds/1 joint or 3 bleeds in diff joints (FR) unaffected by new concentrates Initial dose/frequency: May start 1x/wk dose IU/kg increase rapidly (UK) 50 IU/kg 1x /wk (FR) if started with 1x/wk, unaffected if started 3x/wk consider starting 2x/wk?

15 Recommendations and new concentrates: prophylactic regimen Current FVIII concentrates UK: IU/kg 3-3.5x/wk trough not always >1% lowest dose to prevent bleeds daily dosing more efficient MASAC: IU/kg 3-3.5x levels 1% FR: 3x 30 or 3.5 x IU/kg NL: x IU/kg or according to bleeding Longer-acting FVIII concentrates Studies: Clinical practice: 2x IU/kg 65 IU/kg every 5 days 75 IU/kg once weekly Should we follow the example from the study protocols?

16 Dosing current and long-acting concentrates: children Double dose small effect & frequent dosing still needed

17 Dosing current and long-acting concentrates: children Regimen used In study protocols Twice weekly dosing is very inefficient

18 Dosing current and long-acting concentrates: adults Less infusions are more feasible in adults

19 Recommendations and new concentrates: prophylactic regimen Initiating prophylaxis Continuing prophylaxis By 2nd joint bleed/significant soft tissue bleed May start 1x/wk dose IU/kg increase rapidly Full dose protocol consider starting 2x/wk in stead of 3x/wk?? If half life < 10 hours: Keep at 3-3.5x/wk, perhaps dose If half life 10 hours: Interval hours, dose = Or interval = and dose Consider PK dosing Timing of infusions according ot sports activities!

20 Thank you -Danke Schön