1 European Haemophilia Consortium Round Table of Stakeholders Orthopaedic Aspects in Haemophilia Care What are the goals of treatment? A Haematologist’s perspective Professor Cedric HERMANS MD PhD FRCP (Edin, Lon) Haemostasis and Thrombosis Unit Haemophilia Clinic Division of Haematology Cliniques Universitaires Saint-Luc Catholic University of Louvain 1200 Brussels, Belgium [email protected]
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Prophylaxis in Haemophilia - ehc.eu · European Haemophilia Consortium Round Table of Stakeholders Orthopaedic Aspects in Haemophilia Care What are the goals of treatment? A...
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European Haemophilia Consortium Round Table of Stakeholders
SPINART (Secondary Prophylaxis in Adults, Randomized Trial)
One year mean efficacy results1,2
Optimal treatment strategies for hemophilia: achievements and limitations of current prophylactic regimens.
• Current prophylactic regimens, although very effective, do not completely prevent joint disease in a long-term perspective.
• Joint arthropathy in primary prophylaxis develops over many years, sometimes over a decade or even longer time periods.
• The ankle joints are the first and most severely affected joints in those patients and thus may serve in outcome assessment as an indicator of early joint arthropathy when followed by ultrasound or magnetic resonance imaging.
Patients with Different Lifestyle and Activity Level may need Different FVIII Trough Levels
>3% ?
10% ?
33
34
• Based on FVIII PK parameters
• Based on bleed pattern
• (presence of target joints/joint damage)
• Tailored to activity level (sports)
• Tailored to personal circumstances
• Based on all available information
• Efficient
Hemostasis
Joint Status
Activity Level
Valentino LA. Considerations in individualizing prophylaxis in patients with haemophilia A. Haemophilia 2014 Sep; 20(5): 607-15.
Individualized prophylaxis should be
Standard prophylaxis not optimal for everybody
35
Patient with an average half-life (25 IU/kg every other
day)
Patient with a short half-life (25 IU/kg every other
day) Time spent with FVIII plasma
levels <1%
Increased risk for
break through bleeds
1%
1%
FV
III
leve
l (%
)F
VII
I le
ve
l (%
)
PHARMACOKINETIC DOSINGFV
III:
C (
U/d
L)
6,000 IU/week
1,575 IU/week
770 IU/week
100
10
1
0.1
100
10
1
0.1100
10
1
0.1
0 3 6 9 12 15 18
Time (days)
2000 IU, 3 times a week
450 IU, every 2 days
110 IU, daily
Carlsson et al. Eur J Haematol 1993;51:247–52. JA
« ZERO » bleed world
A new ambition in haemophilia therapy
Not only an issue of treatment availability and intensity
Only achievable with major collaboration of the patient and his family
Aiming for zero bleeds
Lifetime joint bleeds
Joint scores
Normal joints
Moderate damage
Substantial damage
Joint health
Patient impact
Patient–doctor relationship
Funk M et al. Haemophilia 2002; 8:98–103.
4 or more 3 0–2
Physical examination 3–7 0–2 0
X-ray 7–12 0–3 0
MRI 3–8 2 0
Which FVIII Trough Levels are needed for Zero Joint Bleeds?
Den Uijl et al. Haemophilia 2011; 6: 849-53
3%
12%
39
Correlation of endogenous FVIII level and annual
number of joint bleeds
INTEGRATION OF REAL WORLD-DATA COLLECTION, TAILORED CARE AND PATIENT EMPOWERMENT
Personalized Medicine
1. PK profiling
2. Bleeding risk profiling
1. Bleeding phenotype
2. Target joints
3. Joint status
4. Work and sport activity
5. Lifestyle
6. Compliance
3. Bleeding recognition
Patient Empowerment
1. Disease and treatmentunderstanding (adherence) / psychological support
2. Shared treatment and goals decision making (GAS)
3. Life-style and activity adjustment
4. Promotion of self-management
Real-World Data Collection
Treatment tracking
(recording of bleedingepisodes and factor
consumption)
Outcome tracking
Patient-centricprophylaxis
Adapted from Gringeri A, Doralt J, Valentino LA, Crea R, Reininger AJ. Expert Rev Pharmacoecon Outcomes Res. 2016 Jun;16(3):337-45.
Haematological treatment of hemophilia
TODAY TOMORROW
Compensation of defectiveproduction of FVIII or FIX
"Cure"
Factor replacement therapy withplasma-derived or recombinant concentrates
Gene therapy
Non-factor replacement / Disruptive therapy
Endogenous production of natural/unmodified FVIII or FIX
Could IL-1 blockers prevent
blood-induced joint damage in
hemophilia ?
• It would be ideal if there were oral
drugs which could be taken soon
after a joint bleed for a short period
of time during the period
associated with damaging
inflammatory responses along with
CFC replacement to prevent
further bleeding.
• This could be particularly
significant for the vast majority of
patients in the world who do not
have access to prophylaxis with
CFC.
Srivastava A. Blood. 2015 Nov 5;126(19):2175-6.
Antibodies to block TNF-a / IL-1
antiangiogenesisdrugs
Impact of innovation on haemophilia care
More efficient treatments
Persistent control of FVIII or FIX deficiency
Cure of the disease
No BLEEDS
More time and resources for assessing and following non-
bleeding consequences of haemophilia
CONCLUSION
• The goal / ambition of the haematological treatment of haemophilia should be a complete abolition of all bleeding episodes and a full preservation of the musculo-skeletal system
• This is now achievable with current treatment options in a large proportion but not all patients with severe haemophilia
• The focus should be on patients with an Annual Bleeding Rate (ABR) > 0 . In these patients, different strategies should be implemented to better control their disease.