Pharmacokinetic-guided versus standard prophylaxis in hemophilia- A systematic review and meta-analysis

Clinical Division of Hematology and Hemostaseology, Department of Medicine I, Medical University of Vienna, Vienna, Austria. Clinical Division of Hematology and Hemostaseology, Department of Medicine I, Medical University of Vienna, Vienna, Austria; Division of Oncology, Department of Internal Medicine, Medical University of Graz, Graz, Austria. University Library, Medical University of Vienna, Vienna, Austria. Clinical Division of Hematology and Hemostaseology, Department of Medicine I, Medical University of Vienna, Vienna, Austria. Electronic address: ingrid.pabinger@meduniwien.ac.at.

Journal of thrombosis and haemostasis : JTH. 2023
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Abstract
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. OBJECTIVE To assess the efficacy of PK-guided compared to 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 two review authors, we summarized studies qualitatively and synthesized included randomized clinical trials (RCT) quantitatively by fitting random-effects models. RESULTS Search of databases on 3 February 2023 yielded 25 studies fitting our inclusion criteria. Of those, only two RCT and 17 non-randomized 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, non-randomized studies were only presented qualitatively. A random-effects meta-analysis of the two 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 non-randomized studies limited by lack of concurrent controls, heterogeneity in outcome reporting, small sample sizes, and high risk of bias.
Study details
Study Design : Systematic Review
Language : eng
Credits : Bibliographic data from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine