PK-guided switch between standard half-life and extended half-life factor VII products

P117 Introduction: Extended half-life (EHL) factor VIII (FVIII) requires improvements in half-life (t1/2) & area under the curve (AUC) of 1.3 & 1.25 times compared to standard half-life (SHL) products. The aim of this study is compare pharmacokinetics (PK) after the switch from SHL to EHL in patients with hemophilia A (HA). Methods: Multicenter comparative, cross-sectional, prospective study analyzing PK differences after switch from SHL to EHL (ef-moroctocog alfa [rFVIII-Fc] & rurioctocog alfa pegol [PEG-rFVIII]). WAPPS- Hemo® was used to analyze PK parameters with 2-3 samples: t1/2; AUC, peak level (PL); trough level at 24, 48 & 72 hours (TL24, TL48, TL72); & time to reach FVIII levels of 1, 2, 5% (T1%, T2%, T5%). Ratio of t1/2 & AUC, the number of weekly doses & the dose/kg/week before & after the switch were compared. Wilcoxon & Kruskal-Wallis tests (SPSS®) were used to compare the PK parameters. Results: Eightythree patients from 8 Spanish hospitals were analyzed (62 rFVIII-Fc; 21 PEG-rFVIII), 79 had severe HA & 4 moderate HA. Median age was 30 years (range = 3-64) & no differences in weight were observed between both periods.Dose/kg/week & weekly infusion frequency were reduced after the switch to EHL, & significant improvements were observed in all PK parameters after the change from SHL to EHL (Table 1). The median ratios of t1/2 & AUC were 1.3 (IQR:1.2-1.6) and 1.6 (IQR:1.3-2.2) in the entire cohort. In patients with =12 years ratios of t1/2 & AUC were 1.4 (IQR:1.3-1.6) & 1.7 (IQR:1.3-2.3), and in the cohort of 16 patients <12 years treated with rFVIII-Fc were 1.3 (IQR:0.9-1.5) and 1.4 (IQR:1.1- 2.1).After the switch to EHL, median weekly dose frequency (30%, IQR:0-33.3%) & dose/kg/week (16.9%, IQR:8.7-32.8%) were reduced. In a small subset of 15 younger patients the dose/kg/week was increased a median of 28.6% (IQR:11.7-40-7%). No differences were observed in any of the PK parameters & median ratios of t1/2 & AUC in patients aged =12 years treated with rFVIII-Fc vs. PEG-rFVIII (46 rFVIII-Fc; 21 PEG-rFVIII). Discussion/Conclusion: EHL FVIII have shown significant PK improvements in clinical real practice, allowing to reduce weekly infusion number & dose/kg/week. Outside the clinical trial setting, we have observed an increase in t1/2 & AUC ratios accordingly to EHL definition. Comparisons regarding clinical outcomes (bleeding rate after switch) will be performed after a follow-up of 1 year with EHL for the full cohort

Análisis del switch guiado por farmacocinética de factores VIII de semivida estándar a factores de semivida extendida

CO-170 Introducción y objetivos: Los factores VIII (FVIII) de semivida extendida (EHL) han mostrado en los ensayos clínicos mejoras de al menos 1, 3 veces la semivida plasmática (t1/2) y 1, 25 veces el área bajo la curva (AUC) respecto a los FVIII estándar (SHL). Herramientas basadas en modelos farmacocinéticos (PK) poblacionales permiten estimar los parámetros PK individuales y ajustar la profilaxis. El objetivo de este estudio es analizar el switch PK-guiado de SHL a EHL en pacientes con hemofilia A (HA). Métodos: Estudio multicéntrico comparativo, cruzado, prospectivo que analiza las diferencias PK tras el cambio de factores SHL a EHL (Elocta® y Adynovi®) en pacientes con HA grave/moderada en profilaxis. Se ha empleado el PopPK WAPPS-Hemo® con 2-3 muestras para realizar un perfil PK individualizado de los valores de FVIII. Los parámetros PK analizados son: t1/2, AUC, nivel pico (NP), nivel valle a las 24, 48 y/o 72 h (NV24/NV48/NV72) y tiempo para alcanzar niveles de FVIII del 5%, 2% y 1% (T5%/T2%/T1%). También analizamos los ratios de t1/2 y AUC, el nº dosis semanales y la dosis/kg/semana. Para comparar los parámetros PK entre ambos periodos empleamos los test de Wilcoxon y Kruskal-Wallis (SPSS®). Los resultados se expresaron con la mediana y el rango o rango intercuartílico (RIC). Resultados: Se han analizado 64 pacientes procedentes de 8 hospitales españoles (48 switch a Elocta® y 16 a Adynovi®), 62 con HA grave y 2 con HA moderada, con una mediana de edad de 32 años (rango=5-64) y sin diferencias en el peso entre ambos periodo [71, 0 (rango=12-116) vs 72, 0 (16, 9- 116) kg; p=0, 156]. La dosis/kg/semana se redujo tras el switch a EHL [74, 5 (RIC:59, 2-108, 1) vs 69, 2 (RIC:46, 2-96, 7) UI/kg/semana; p<0, 0001], así como ..

A decade of changes in management of immune thrombocytopenia, with special focus on elderly patients

Gent gran; Pautes; TPO-RAAncianos; Pautas; TPO-RAElderly; Guidelines; TPO-RABackground Ten years after their availability, thrombopoietin receptor agonists (TPO-RA) have heralded a paradigm shift in the treatment of immune thrombocytopenia (ITP). This study was aimed to analyze the implementation of current recommendations in the standard practice of adult ITP patients, and how age may influence those changes. Methods We included 121 adult patients (> 65 years, n = 54; younger individuals, n = 67) who initiated treatment with TPO-RA between January 2012 and December 2014. Results Patients older than 65 years treated with TPO-RA presented at diagnosis with significantly higher platelet counts, less bleeding, and a more prothrombotic profile than younger ones. The high efficacy rates of TPO-RA, preferentially used during the last decade in non-chronic phases, precluded from further therapies in the majority of ITP patients. Their administration was associated with a sharp decline in the last decade in the use of splenectomy and intravenous immunoglobulin, especially in younger ITP individuals. Conclusion These results confirm (1) that there is a preferential use of TPO-RAs in elderly ITP patients with fewer bleeding complications but more unfavorable prothrombotic conditions than in younger individuals, and (2) that early use of these agents has been established as an effective therapeutic alternative to other second line therapies.This work was supported by Amgen S.A. Spain. Amgen did not have any role in study design, collection, analysis, and interpretation of data, writing the report, or in the decision to submit the report for publication

FVIII inhibitor development according to concentrate: Data from the EUHASS registry excluding overlap with other studies

PubMed ID: 26208036[No abstract available