Targeting an elevated FVIII level using personalized rurioctocog alfa pegol prophylaxis in specific patient populations with hemophilia A: post hoc subanalysis of the randomized, phase 3 PROPEL study

HZRM Hämophilie-Zentrum Rhein Main, Mörfelden-Walldorf, Germany. Vivantes Klinikum im Friedrichshain, Berlin, Germany. The University of Texas Health Science Center at Houston, Houston, TX, USA. National Academy of Medical Sciences of Ukraine, Lviv, Ukraine. Takeda Development Center Americas, Inc., 650 East Kendall Street, Cambridge, MA 02142, USA. Baxalta Innovations GmbH, a Takeda Company, Vienna, Austria. Takeda Pharmaceuticals International AG, Zurich, Switzerland. Katharine Dormandy Haemophilia and Thrombosis Centre, Royal Free Hospital, London, UK. Department of Hemostasis Disorders and Internal Medicine, Institute of Hematology and Transfusion Medicine, Warsaw, Poland.

Therapeutic advances in hematology. 2023;14:20406207231178596
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Abstract
BACKGROUND The phase 3, prospective PROPEL study demonstrated that pharmacokinetic (PK)-guided prophylaxis targeting elevated factor VIII (FVIII) troughs in patients with hemophilia A resulted in lower annualized bleeding rates (ABRs) and a higher proportion of patients experiencing zero bleeds in the second 6 months of treatment when targeting a FVIII trough of 8-12% versus 1-3%. OBJECTIVE To investigate the benefit of PK-guided prophylaxis with rurioctocog alfa pegol targeting two FVIII trough levels in specific patient subgroups in a post hoc analysis using data from PROPEL. DESIGN This is a post hoc analysis of data from the PROPEL study. The design and primary outcomes of the prospective, randomized PROPEL study (NCT02585960) have been reported previously. METHODS This post hoc analysis reports data stratified by FVIII half-life (t(1/2)), hemophilic arthropathy status, number of target joints at screening, previous treatment regimen, and ABR range in the 12 months before study entry. RESULTS Targeting an elevated FVIII trough of 8-12% was associated with higher average FVIII levels over time, regardless of FVIII t(1/2) at baseline. The decrease in total ABR between the 8-12% and 1-3% arms was greatest in patients with a FVIII t(1/2) of 6 to <12 h (0.7 versus 3.5); a higher number of target joints, that is, at least four target joints, at baseline (0.2 versus 1.6); the presence of arthropathy (0.1 versus 1.7); and those previously treated on-demand (0.3 versus 1.8). CONCLUSION These results support the feasibility of targeting elevated FVIII levels using personalized rurioctocog alfa pegol prophylaxis. These benefits may be especially important in patients with a short FVIII t(1/2) and those receiving standard prophylaxis with frequent breakthrough bleeds, arthropathy, and target joints. REGISTRATION ClinicalTrials.gov Identifier: NCT02585960; https://clinicaltrials.gov/ct2/show/NCT02585960.
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Language : eng
Credits : Bibliographic data from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine