Rurioctocog alfa pegol PK-guided prophylaxis in hemophilia A: results from the phase 3 PROPEL study
Autor: | Werner Engl, Oleksandra Stasyshyn, Hishamshah Ibrahim, Vlad C. Radulescu, Robert Klamroth, William J. Savage, Bruce Ewenstein, Peter William Collins, Jerzy Windyga, Srilatha Tangada |
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Jazyk: | angličtina |
Rok vydání: | 2021 |
Předmět: |
Adult
Male medicine.medical_specialty Adolescent Immunology Personalized treatment Severe disease Hemorrhage 030204 cardiovascular system & hematology Hemophilia A Biochemistry Thrombosis and Hemostasis Young Adult 03 medical and health sciences 0302 clinical medicine Pharmacokinetics Internal medicine Clinical endpoint Medicine Humans Prospective Studies Adverse effect Factor VIII Coagulants business.industry Cell Biology Hematology Middle Aged Confidence interval Safety profile Treatment Outcome 030220 oncology & carcinogenesis Female business Dosing Frequency |
Zdroj: | Blood |
ISSN: | 0258-5960 |
Popis: | 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. |
Databáze: | OpenAIRE |
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