Modeling to Predict Factor VIII Levels Associated with Zero Bleeds in Patients with Severe Hemophilia A Initiated on Tertiary Prophylaxis.
Adolescent
Adult
Canada
Child
Europe
Factor VIII
/ administration & dosage
Hemarthrosis
/ blood
Hemophilia A
/ blood
Hemostasis
/ drug effects
Hemostatics
/ administration & dosage
Humans
Middle Aged
Models, Biological
Risk Factors
Severity of Illness Index
Tertiary Prevention
United States
Young Adult
Journal
Thrombosis and haemostasis
ISSN: 2567-689X
Titre abrégé: Thromb Haemost
Pays: Germany
ID NLM: 7608063
Informations de publication
Date de publication:
May 2020
May 2020
Historique:
entrez:
6
5
2020
pubmed:
6
5
2020
medline:
25
8
2020
Statut:
ppublish
Résumé
Factor VIII (FVIII) trough levels > 1 IU/dL in patients with severe hemophilia A receiving regular prophylaxis may optimize bleed protection. In this post hoc analysis of patients receiving tertiary prophylaxis for approximately 1 year, the relationship between estimated FVIII levels and reported bleeds was investigated to predict the potential for zero bleeds. Sixty-three patients (median [range] age, 28 [7-59] years) with severe hemophilia A (229 bleeds) were included. FVIII levels at time of each bleed were estimated from single-dose individual pharmacokinetics. The highest estimated FVIII level at which patients experienced a bleed was considered the "potentially effective trough level" for that bleed type. Kaplan-Meier estimates of proportions of patients with no bleeds above certain estimated FVIII levels were determined. Those not experiencing a bleed in the trial were assumed to have a bleed at 0 IU/dL (pragmatic approach) or at their median trough level (conservative approach). Kaplan-Meier estimates based on pragmatic approach predicted zero all bleeds, joint bleeds, and spontaneous joint bleeds in 1 year in 40, 43, and 63% of patients, respectively, when the potentially effective trough FVIII level was set at 1 IU/dL. Between 1 and 10 IU/dL, every 1 IU/dL rise in estimated FVIII level was associated with an additional 2% of patients having zero all bleeds. This post hoc analysis confirms benefits with trough levels of approximately 1 to 3 IU/dL in most patients starting tertiary prophylaxis; prophylaxis with higher trough levels may help patients to achieve zero bleeds.
Sections du résumé
BACKGROUND
BACKGROUND
Factor VIII (FVIII) trough levels > 1 IU/dL in patients with severe hemophilia A receiving regular prophylaxis may optimize bleed protection.
OBJECTIVES
OBJECTIVE
In this post hoc analysis of patients receiving tertiary prophylaxis for approximately 1 year, the relationship between estimated FVIII levels and reported bleeds was investigated to predict the potential for zero bleeds.
METHODS
METHODS
Sixty-three patients (median [range] age, 28 [7-59] years) with severe hemophilia A (229 bleeds) were included. FVIII levels at time of each bleed were estimated from single-dose individual pharmacokinetics. The highest estimated FVIII level at which patients experienced a bleed was considered the "potentially effective trough level" for that bleed type. Kaplan-Meier estimates of proportions of patients with no bleeds above certain estimated FVIII levels were determined. Those not experiencing a bleed in the trial were assumed to have a bleed at 0 IU/dL (pragmatic approach) or at their median trough level (conservative approach).
RESULTS
RESULTS
Kaplan-Meier estimates based on pragmatic approach predicted zero all bleeds, joint bleeds, and spontaneous joint bleeds in 1 year in 40, 43, and 63% of patients, respectively, when the potentially effective trough FVIII level was set at 1 IU/dL. Between 1 and 10 IU/dL, every 1 IU/dL rise in estimated FVIII level was associated with an additional 2% of patients having zero all bleeds.
CONCLUSION
CONCLUSIONS
This post hoc analysis confirms benefits with trough levels of approximately 1 to 3 IU/dL in most patients starting tertiary prophylaxis; prophylaxis with higher trough levels may help patients to achieve zero bleeds.
Identifiants
pubmed: 32369844
doi: 10.1055/s-0040-1709519
doi:
Substances chimiques
Hemostatics
0
F8 protein, human
839MOZ74GK
Factor VIII
9001-27-8
Types de publication
Journal Article
Multicenter Study
Randomized Controlled Trial
Langues
eng
Sous-ensembles de citation
IM
Pagination
728-736Informations de copyright
Georg Thieme Verlag KG Stuttgart · New York.
Déclaration de conflit d'intérêts
All authors report nonfinancial (medical writing) support from Baxalta US Inc., a Takeda company, during the conduct of the study. P.C. has received consulting fees from Bayer, Baxalta