000096821 001__ 96821
000096821 005__ 20210902121854.0
000096821 0248_ $$2sideral$$a116377
000096821 037__ $$aART-2020-116377
000096821 041__ $$aeng
000096821 100__ $$aMegías Vericat, J.E.
000096821 245__ $$aPK-guided switch between standard half-life and extended half-life factor VII products
000096821 260__ $$c2020
000096821 5060_ $$aAccess copy available to the general public$$fUnrestricted
000096821 5203_ $$aP117
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.
000096821 540__ $$9info:eu-repo/semantics/openAccess$$aAll rights reserved$$uhttp://www.europeana.eu/rights/rr-f/
000096821 590__ $$a4.287$$b2020
000096821 591__ $$aHEMATOLOGY$$b27 / 76 = 0.355$$c2020$$dQ2$$eT2
000096821 592__ $$a1.213$$b2020
000096821 593__ $$aGenetics (clinical)$$c2020$$dQ1
000096821 593__ $$aMedicine (miscellaneous)$$c2020$$dQ1
000096821 593__ $$aHematology$$c2020$$dQ1
000096821 655_4 $$ainfo:eu-repo/semantics/conferenceObject$$vinfo:eu-repo/semantics/publishedVersion
000096821 700__ $$aBonanad-Boix, S.
000096821 700__ $$aMartínez García, M.F.
000096821 700__ $$aBerrueco, R.
000096821 700__ $$aMingot-Castellano, M.E.
000096821 700__ $$aRodríguez, M.
000096821 700__ $$aCanaro, M.
000096821 700__ $$aMateu, J.
000096821 700__ $$aLarrode, I.
000096821 700__ $$aHaya, S.
000096821 700__ $$aSantamaria, A.
000096821 700__ $$aMesegue, M.
000096821 700__ $$aAlbo, C.
000096821 700__ $$aPalomero, A.
000096821 700__ $$aVilalta, N.
000096821 700__ $$0(orcid)0000-0001-5408-9264$$aCalvo, J.M.$$uUniversidad de Zaragoza
000096821 700__ $$aCid, A.R.
000096821 700__ $$aPoveda, J.L.
000096821 700__ $$aIorio, A.
000096821 7102_ $$11007$$2610$$aUniversidad de Zaragoza$$bDpto. Medicina, Psiqu. y Derm.$$cArea Medicina
000096821 773__ $$g26, S2 (2020), P117 [88-89]$$pHaemophilia$$tHAEMOPHILIA$$x1351-8216
000096821 8564_ $$s237414$$uhttps://zaguan.unizar.es/record/96821/files/texto_completo.pdf$$yVersión publicada
000096821 8564_ $$s683160$$uhttps://zaguan.unizar.es/record/96821/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
000096821 909CO $$ooai:zaguan.unizar.es:96821$$particulos$$pdriver
000096821 951__ $$a2021-09-02-10:31:22
000096821 980__ $$aARTICLE