Background The high inter-individual variability in pharmacokinetics (PK) of factor VIII (FVIII) justifies the use of PK-guided prophylaxis, especially in switching between different products. A proposed definition of extended half-life (EHL) FVIII requires improvements of at least 1.3 times in half-life (t1/2) and 1.25 times the area under the curve (AUC) compared to standard half-life (SHL) products (Mahlangu et al. Haemophilia. 2018;24(3):348-358). The objective of this multicenter study was to analyze the results of a PK-guided switch from SHL to EHL in patients with hemophilia A (HA). Methods Multicenter comparative, cross-sectional, prospective study in HA severe/moderate patients in prophylaxis analyzing PK differences after switch from SHL to EHL (efmoroctocog alfa [rFVIII-Fc] and 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 and 72 h (TL24, TL48, TL72); and time to reach FVIII levels of 1, 2, 5% (T1%, T2%, T5%). We have also compared the ratio of t1/2 and AUC, the number of weekly doses and the dose/kg/week before and after the switch. Wilcoxon and Kruskal-Wallis tests (SPSS®) were used to compare the PK parameters. Results are expressed with the median and interquartile range (IQR) or range, and mean and standard deviation (SD). Results Eighty-one patients from 8 Spanish hospitals were analyzed (61 rFVIII-Fc; 20 PEG-rFVIII), 78 had severe HA and 3 moderate HA. Mean age was 30 years (range=3-64) and no differences in weight were observed between both periods [70 (range=12-116) vs 70 (13.7-116) kg; p=0,141]. Dose/kg/week and weekly infusion frequency were reduced after the switch to EHL, and significant improvements were observed in all PK parameters after the change from SHL to EHL (Table 1). These results were similar in adult and pediatric patients switching to rFVIII-Fc. The median ratios of t1/2 and AUC were 1.3 (IQR:1.2-1.6) and 1.5 (IQR:1.3-2.3) in the entire cohort. These results were reproduced in the subset of patients with ≥12 years treated with rFVIII-Fc and PEG-rFVIII (ratio t1/2: 1.4 [IQR:1.3-1.6]; ratio AUC: 1.6 [IQR:1.3-2.3]), and were slightly in the cohort of 15 patients <12 years treated with rFVIII-Fc (ratio t1/2: 1.3 [IQR:0.9-1.3]; ratio AUC: 1.3 [IQR:1.1-1.9]), the only EHL approved in Europe for children. After the switch to EHL, weekly dose frequency (median 23.3%, IQR:0-33.3%) and dose/kg/week (median 16%, IQR:5.3-30%) were reduced. In a small subset of 17 patients the dose/kg/week increased a median of 31.4%, and this subset was younger than the patients with dose/kg/week reduction or no changes (median age 18 [IQR:8-22] vs. 33 [IQR:16.5-42.5]). No differences were observed in any of the PK parameters and median ratios of t1/2 and AUC in patients aged ≥12 years treated with rFVIII-Fc vs. PEG-rFVIII (46 rFVIII-Fc; 20 PEG-rFVIII; Table 2). Conclusions EHL FVIII have shown significant PK improvements in clinical real practice, allowing to reduce weekly infusion number and dose/kg/week, especially in adult patients. Outside the clinical trial setting, we have observed an increase in t1/2 and 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. WAPPS-Hemo PK-guided switch easily facilitates individualization of prophylaxis with a potential reduction in the cost of treatment and patient perceived outcomes. Disclosures Megias: Baxalta US INC.: Research Funding; Grifols: Research Funding. Bonanad Boix:Baxalta US INC.: Research Funding. Berrueco:NovoNordisk: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; SOBI: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Bayer: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; CSL-Bering: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Mingot-Castellano:Sobi: Consultancy; Bayer: Consultancy; Amgen: Consultancy; Roche: Consultancy; Novartis: Consultancy; Novonordisk: Consultancy; Takeda: Consultancy; CSL Behring: Consultancy. Cid:Shire, a Takeda company: Honoraria; Novo Nordisk: Honoraria. Sanz:AbbVie: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Membership on an entity's Board of Directors or advisory committees, Research Funding; Boehringer-Ingelheim: Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Helsinn Healthcare: Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen - Cilag: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Onconova: Membership on an entity's Board of Directors or advisory committees, Research Funding; Hoffman - La Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding.

Introduction: Rare bleeding disorders (RBD) constitute 5% of total hereditary bleeding disorders, although the number could be higher, due to the presence of undiagnosed asymptomatic patients. The objective of this study was to analyze the prevalence and characteristics of patients with severe RBDs in our area. Material and methods: We analyzed the patients with RBD followed at a tertiary‐level hospital between January 2014 and December 2021. Results: A total of 101 patients were analyzed, with a median age at diagnosis of 27.67 years (range 0–89), of which 52.47% were male. The most frequent RBD in our population was FVII deficiency. Regarding the diagnostic reason, the most frequent cause was a preoperative test and only 14.8% reported bleeding symptoms at the time of diagnosis. A genetic study was carried out in 63.36% of patients and the most frequent mutation type found was finding a missense mutation. Conclusions: The distribution of RBDs in our centre is similar to the one reported in the literature. The majority of RBDs were diagnosed from a preoperative test and this allowed preventive treatment prior to invasive procedures to avoid bleeding complications. 83% of patients did not have a pathological bleeding phenotype according to ISTH‐BAT

Background:Prophylactic treatment with standard half-life coagulation factors (SHL) requires 3-4 weekly periodic infusions. Extended half-life (EHL) factor VIII (FVIII) provides improvements in half-life (t1/2) and area under the curve (AUC) of 1.3 and 1.25 times compared to standard half-life (SHL) products. Rurioctocog alfa pegol is an extended half-life (EHL) rFVIII (rFVIII-EHL) treatment that could be a more convenient and cost-effective therapeutic alternative than SHL, since it would reduce the number of weekly infusions (NWI). Aims:The aim of this study is to analyze pharmacokinetic (PK) parameters and compare NWI and bleeding rates after switching from SHL to this EHL in hemophilia A (HA) patients. Methods:In a prospective study, the number of weekly infusions (NWI), annualized bleeding rate (ABR), annualized joint bleeding rate (AJBR), and PK parameters were compared between previous treatment with FVIII-SHL vs rFVIII-EHL (Rurioctocog alfa pegol). The assessment of the PK parameters: volume of distribution (Vd (dL/kg)), clearance (Cl (dL/h/kg)) and half-life time (t½ (h)) was performed by using the pharmacokinetic poblacional software online myPKFiT®. Results:Nineteen patients from 2 Spanish hospitals (n=12 Vall d'Hebron Hospital, n=7 Hospital Regional Universitario de Málaga) were recruited. Median age was 30 years (range, 12-54), with five pediatric patients, and 18 had severe HA (one moderate HA). Sixteen patients were under prophylactic treatment with Advate® and 1 with Kovaltry®. Two patients were switched from on-demand treatment to prophylaxis. The median use of rFVIII-EHL was 15.63 month. The PK parameters after the switch to the rFVIII-EHL in entire cohort and pediatric cohort are shown in Table 1. The t ½ of rFVIII-EHL was positively correlated to preinfusion plasma levels of von Willebrand factor antigen (vWF:Ag) (Figure 1). ABR and AJBR were reduced, as well as weekly infusion frequency (33.3%, IQR:0-50%) (Table 2). Of note, 57.9% of patients presented zero joint bleeding events after switchingtorFVIII-EHL. Conclusions:In this prospective analysis rFVIII- EHL presents as a therapeutic alternative that allows reducing ABR and AJBR as well as weekly infusion frequency according to PK patient parameters. Disclosures Bosch: Roche:Honoraria;Celgene:Honoraria;Jansen:Honoraria;Abbvie:Honoraria;Novartis:Honoraria;Astra Zeneca:Honoraria;Takeda:Honoraria.Gironella Mesa:Bristol Myers Squibb:Honoraria, Speakers Bureau;Janssen:Consultancy, Honoraria.

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