[Translated article] Pharmacokinetic-guided switching from standard half-life factor VIII to extended half-life pegylated factor VIII in haemophilia A therapy in clinical practice
Bibliographic record
Abstract
To analyse the differences in pharmacokinetic and clinical parameters (bleeding rates and joint health) before and after switching from standard half-life factor VIII (FVIII) to extended half-life pegylated FVIII in patients with severe/moderate haemophilia A on prophylaxis, 1 year before and after the switch in real-life. This is a single-centre, comparative, observational, sequential, retrospective, and multidisciplinary study. Population pharmacokinetic models from the WAPPS-Hemo® application were used to calculate pharmacokinetic parameters and individualise prophylaxis. The annual rate of total and joint bleeds, joint health (Haemophilia Joint Health Score), plasma half-life and area under the curve ratios, FVIII consumption, administration frequency, and cost were analysed. Thirty-eight adult patients with haemophilia A who switched from standard half-life FVIII to extended half-life pegylated FVIII were analysed. Significant improvements ( P < .05) were observed in all pharmacokinetic parameters, with plasma half-life and area under the curve improvement ratios of 1.5 and 1.9, respectively, as well as reductions in annual total and joint bleeding rates. A higher number of patients with zero total (16.0 vs. 29.0) and joint bleeds (23.0 vs. 33.0) was also observed. The median reductions in administration frequency and dose/kg/week were 30.0% and 19.7%, respectively, avoiding 44.3 infusions/patient/year, resulting in savings of 20,843 €/patient/year. Furthermore, joint health improved (23.0 vs. 21.0; P = .017), and target joints resolved after the switch. The pharmacokinetically guided switch from standard half-life FVIII to pegylated FVIII demonstrated significant clinical benefits with reduced bleeding rates and improvements in joint health. Additionally, improvements in pharmacokinetic parameters were observed, allowing for reduced treatment burden by decreasing administration frequency, as well as lower consumption and costs. Analizar las diferencias en los parámetros farmacocinéticos y clínicos (tasas de sangrado y salud articular) antes y después del intercambio de factores VIII (FVIII) de vida media estándar a FVIII de vida media extendida pegilados en pacientes con hemofilia A grave/moderada en profilaxis, un año antes y después del intercambio en vida real. Estudio unicéntrico comparativo, observacional, secuencial, retrospectivo y multidisciplinar. Se emplearon los modelos farmacocinéticos poblacionales de la aplicación WAPPS-Hemo® para calcular los parámetros farmacocinéticos e individualizar la profilaxis. Se analizó la tasa anual de sangrados totales y articulares, la salud articular (Haemophilia Joint Health Score) , la ratio semivida plasmática y área bajo la curva, el consumo de FVIII, la frecuencia de administración y el coste. Se analizaron 38 pacientes adultos con hemofilia A que cambiaron de tratamiento de FVIII de vida media estándar a FVIII de vida media extendida pegilados. Mejoraron significativamente (p < 0,05) todos los parámetros farmacocinéticos, con ratios de mejora de semivida plasmática y área bajo la curva de 1,5 y 1,9, y se registraron reducciones en tasa anual de sangrados totales y articulares, y un mayor número de pacientes con cero sangrados totales (16,0 vs 29,0) y articulares (23,0 vs 33,0). Las medianas de reducción en frecuencia de administración y dosis/kg/semana fueron de un 30,0% y 19,7%, respectivamente, evitando 44,3 infusiones/paciente/año, lo que supuso un ahorro de 20.843 €/paciente/año. Además, se observaron mejoras en la salud articular (23,0 vs 21,0; p = 0,017) y se resolvieron las articulaciones diana tras el intercambio. El intercambio guiado por farmacocinética de FVIII de vida media estándar a FVIII pegilados ha demostrado un beneficio clínico significativo con tasas reducidas de sangrado y mejoras en la salud articular. Así mismo, también se observaron mejoras en los parámetros farmacocinéticos, lo que permitió disminuir tanto la carga de tratamiento, al reducir la frecuencia de administración en los pacientes, como el consumo y el coste.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.004 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.006 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".