The development of inhibitors has remained as the most dreadful complication of hemophilia
treatment, with huge consequences both on patients’ quality of life and on societal costs. We have performed several projects in trying to shed new light
on the mechanisms behind inhibitor development and course.
A) Meta-analysis of the evidence about inhibitor development in previously treated patients (PTPs)
This was a project funded within the framework of the European Hemophilia Surveillance Scheme,
reported in the Journal of Thrombosis and Haemostasis.
B) Individual Patient Data Meta-Analysis on the Determinant of Risk Inhibitor Development in Previously Untreated
This was a collaborative work, sponsored as a working party of the European Association for Hemophilia and Allied Disorders (EAHAD).
C) Investigations of the Determinant of Inhibitor Development in PTPs and Study of Their Clinical Course
This is an ongoing project with two components. The first is a reassessment of all the published
cases of inhibitors developed in PTPs (sponsored by CHS within the granting opportunity Care until Cure); the second is the same investigations
performed for the inhibitors reported to EUHASS (funded as IIT by Pfizer Canada).
The study is ongoing.
The decision box project aims to create two-sided decision tools - a decision box for the physician
and a corresponding patient decision aid - to facilitate shared decision making for treatment decisions in haemophilia. These tools are designed to be
used contemporaneously to prepare both parties for a clinical encounter where both parties can come together to make an informed, evidence-based,
value-driven decision about a hemophilia treatment decision. Each tool contains information about the decision to be considered, treatment options, and
Scientific evidence about the benefits and harms of each option.
Currently, the three areas for which these decision tools have been completed are:
1) Starting prophylaxis treatment in previously untreated patients: when and what dose,
2) Choice of factor concentrate: either recombinant or plasma-derived, and
3) Starting immune tolerance induction for factor inhibitory antibodies: when and what dose. Decision tools for a fourth area- Starting secondary
prophylaxis in previously treated adults- are being completed.
Decision Box 1:
Decision Box 2 :
Decision Box 3:
Decision Box 1:
Decision Box 2:
Decision Box 3:
This is a project aiming at exploiting all the evidence collected with this peculiar study design,
with focus on both the specific factor VIII for which we gathered data (ADVATE) and for the analysis method. This project is supported by the
manufacturer of Advate (Baxter HealthCare) and by MITACS grants for the learners involved.
Phase I has been completed and reported
Phase II and III are ongoing, dealing respectively with the analysis of a subpopulation of patients with uncertain risk of inhibitors and on
methodological challenges in performing these studies
The WAPPS-Hemo service will empower hemophillia treatment by making it easier to perform individual pharmacokinetic (PK) assessment. The WAPPS-Hemo service will allow for the robust estimation of individual PK parameters with a reduced number of plasma samples. It will also enhance knowledge about the PK of factor VIII and IX.