Rurioctocog alfa pegol PK-guided prophylaxis in hemophilia A: results from the phase 3 PROPEL study.

Autor:	Klamroth R; Department for Internal Medicine, Vascular Medicine and Haemostaseology, Vivantes Klinikum Friedrichshain, Berlin, Germany., Windyga J; Department of Hemostasis Disorders and Internal Medicine, Institute of Hematology and Transfusion Medicine, Warsaw, Poland., Radulescu V; Hemophilia Treatment Center, University of Kentucky, Lexington, KY., Collins PW; Institute of Infection and Immunity, School of Medicine, Cardiff University, Cardiff, United Kingdom., Stasyshyn O; Academy of Medical Sciences of Ukraine, Lviv, Ukraine., Ibrahim HM; Pediatric Department, Hospital Kuala Lumpur, Kuala Lumpur, Malaysia., Engl W; Baxalta Innovations GmbH, a Takeda company, Vienna, Austria; and., Tangada SD; Baxalta US Inc, a Takeda company, Cambridge, MA., Savage W; Baxalta US Inc, a Takeda company, Cambridge, MA., Ewenstein B; Baxalta US Inc, a Takeda company, Cambridge, MA.
Jazyk:	angličtina
Zdroj:	Blood [Blood] 2021 Apr 01; Vol. 137 (13), pp. 1818-1827.
DOI:	10.1182/blood.2020005673
Abstrakt:	Rurioctocog alfa pegol prophylaxis targeting factor VIII (FVIII) troughs ≥1% has shown to be efficacious with an acceptable safety profile in people with hemophilia A (PwHA). The PROPEL trial compared safety and efficacy of 2 target FVIII troughs in PwHA aged 12 to 65 years, with severe disease, annualized bleeding rate ≥2, and previous FVIII treatment. PwHA were randomized to 12 months' pharmacokinetic (PK)-guided rurioctocog alfa pegol prophylaxis targeting FVIII troughs of 1% to 3% (reference arm) or 8% to 12% (elevated arm); first 6 months was treatment-adjustment period. The primary endpoint was absence of bleeds during the second 6 months, analyzed using multiple imputations (full analysis set [FAS]). In the 1% to 3% and 8% to 12% arms, respectively, point estimates (95% confidence interval) of proportions of PwHA with zero total bleeds were 42% (29% to 55%) and 62% (49% to 75%) in FAS (N = 115; P = .055) and 40% (27% to 55%) and 67% (52% to 81%) in per-protocol analysis set (N = 95; P = .015). Dosing frequency and consumption varied in each arm. Adverse events (AEs) occurred in 70/115 (60.9%) PwHA; serious AEs in 7/115 (6%) PwHA, including 1 treatment-related in 8% to 12% arm (transient anti-FVIII inhibitor). There were no deaths, serious thrombotic events, or AE-related discontinuations. PK-guided prophylaxis was achievable and efficacious in both arms. No new safety signals were observed in the 8% to 12% arm. These results demonstrate elevated FVIII troughs can increase the proportion of PwHA with zero bleeds and emphasize the importance of personalized treatment. This trial was registered at www.clinicaltrials.gov as #NCT02585960. (© 2021 by The American Society of Hematology.)
Databáze:	MEDLINE
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