Pharmacokinetic-guided versus standard prophylaxis in hemophilia: a systematic review and meta-analysis.
factor IX
factor VIII
hemophilia A
hemophilia B
hemorrhage
systematic review
Journal
Journal of thrombosis and haemostasis : JTH
ISSN: 1538-7836
Titre abrégé: J Thromb Haemost
Pays: England
ID NLM: 101170508
Informations de publication
Date de publication:
12 2023
12 2023
Historique:
received:
10
03
2023
revised:
11
08
2023
accepted:
29
08
2023
medline:
27
11
2023
pubmed:
23
9
2023
entrez:
22
9
2023
Statut:
ppublish
Résumé
With population pharmacokinetic (PK) modeling more readily available and PK-guided prophylaxis endorsed by current hemophilia guidelines, we conducted a systematic review to summarize current evidence in the literature. To assess the efficacy of PK-guided compared with non-PK-guided prophylaxis. We did not restrict inclusion to specific study design labels and included all studies consisting of at least one distinct cohort arm receiving PK-guided prophylaxis. We searched the following databases from inception to date of search: MEDLINE, Embase, CENTRAL, ClinicalTrials.gov, and the EU Clinical Trial Register. Following title, abstract, and full-text screening conducted independently by 2 review authors, we summarized studies qualitatively and synthesized included randomized clinical trials (RCTs) quantitatively by fitting random-effects models. Search of databases on February 3, 2023, yielded 25 studies fitting our inclusion criteria. Of those, only 2 RCTs and 17 nonrandomized studies included a standard prophylaxis comparator group. Furthermore, risk of bias in the latter was substantial, primarily due to before-after study designs and retrospective comparator groups. Thus, nonrandomized studies were only presented qualitatively. A random-effects meta-analysis of the 2 identified RCT remained inconclusive with regards to bleeding outcomes (ratio of means, 1.15; 95% CI, 0.85-1.56) and factor consumption (ratio of means, 0.82; 95% CI, 0.58-1.18). Evidence in the literature suggesting a clinical benefit of PK-guided over standard fixed-dose prophylaxis was weak and mainly found in nonrandomized studies limited by lack of concurrent controls, heterogeneity in outcome reporting, small sample sizes, and high risk of bias.
Sections du résumé
BACKGROUND
With population pharmacokinetic (PK) modeling more readily available and PK-guided prophylaxis endorsed by current hemophilia guidelines, we conducted a systematic review to summarize current evidence in the literature.
OBJECTIVES
To assess the efficacy of PK-guided compared with non-PK-guided prophylaxis.
METHODS
We did not restrict inclusion to specific study design labels and included all studies consisting of at least one distinct cohort arm receiving PK-guided prophylaxis. We searched the following databases from inception to date of search: MEDLINE, Embase, CENTRAL, ClinicalTrials.gov, and the EU Clinical Trial Register. Following title, abstract, and full-text screening conducted independently by 2 review authors, we summarized studies qualitatively and synthesized included randomized clinical trials (RCTs) quantitatively by fitting random-effects models.
RESULTS
Search of databases on February 3, 2023, yielded 25 studies fitting our inclusion criteria. Of those, only 2 RCTs and 17 nonrandomized studies included a standard prophylaxis comparator group. Furthermore, risk of bias in the latter was substantial, primarily due to before-after study designs and retrospective comparator groups. Thus, nonrandomized studies were only presented qualitatively. A random-effects meta-analysis of the 2 identified RCT remained inconclusive with regards to bleeding outcomes (ratio of means, 1.15; 95% CI, 0.85-1.56) and factor consumption (ratio of means, 0.82; 95% CI, 0.58-1.18).
CONCLUSION
Evidence in the literature suggesting a clinical benefit of PK-guided over standard fixed-dose prophylaxis was weak and mainly found in nonrandomized studies limited by lack of concurrent controls, heterogeneity in outcome reporting, small sample sizes, and high risk of bias.
Identifiants
pubmed: 37739039
pii: S1538-7836(23)00662-1
doi: 10.1016/j.jtha.2023.08.031
pii:
doi:
Types de publication
Meta-Analysis
Systematic Review
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
3432-3449Informations de copyright
Copyright © 2023 International Society on Thrombosis and Haemostasis. Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of competing interests B.W. and F.M. have no conflicts of interest to declare. C.A. received personal fees for lectures and/or participation in advisory boards from Bayer, CSL Behring, Sobi, Roche, Takeda, LFB, and Novo Nordisk. D.K. has received honoraria for advisory boards from CSL Behring. I.P. is a consultant for CSL Behring and has received honoraria for lectures and advisory board sessions from Bayer, CSL Behring, Pfizer, Roche, Sobi, and Takeda and a research grant to the Institution from CSL Behring and Sobi. O.K. has received honoraria for advisory boards from CSL Behring.