Not All Patients Benefit from Switching to Ehl: Results from the Wapps Database

Abstract

Introduction: Extended Half-Life (EHL) concentrates were recently introduced to increase trough levels, decrease infusion frequency and potentially limiting the burden of treatment in patients with haemophilia (PWH) and their caregivers. Group-based studies have reported increased terminal half-life (THL) after switching from standard half-life (SHL) to EHL concentrates. However, available reports have included less than 30 patients and large-scale studies on switching from SHL to EHL concentrates are lacking. Aim: to assess individual changes in THL after switching from SHL to EHL concentrates in patients with severe haemophilia. Methods: Data were collected from the WAPPS (Web-Accessible Population Pharmacokinetics Service; www.wapps-hemo.org) database, which aims to assemble a database of pharmacokinetic data in PWH, develop and validate population pharmacokinetics models, and integrate these models within a Web-based calculator for individualized pharmacokinetic estimation. Informed consent was waived by the ethical committee. Data were selected from patients with both SHL and EHL infusions available. In case of multiple data, the last SHL and first EHL infusion were selected. THL was compared according to haemophilia type and age groups (children/adults). Comparisons were made based on haemophilia type and age by means of non-parametric paired testing. Results: Data were collected from 649 patients (1298 infusions) with severe haemophilia (89% haemophilia A; median age: 21.7 (11.5-37.7), weight: 66.0 kg (43.6-80.0) BMI: 22.5 (18.9-25.3); positive inhibitor history: 11.7%). All patients had received both SHL and EHL infusions. THL increased by a median factor 1.4 (1.2-1.7) in FVIII, leading to an absolute median increase of 4.1 hours (IQR: 2.0-6.7). However, THL was extended by less than 20% in 157 (27,2%) patients with haemophilia A after switching to EHL concentrates, leading to less than 48 minutes extension of THL. THL showed a decrease in 57 (9,9%) patients with haemophilia A after switching. For patients switching to EHL FIX, THL increased by a median factor 3.1 (2.4-3.6), leading to a median extension of 70.3 (52.5-90.8) hours in THL of FIX. All patients with haemophilia B showed an extension of THL after switching, with a minimum increase of 25%. Both the absolute and the relative increase in THL were similar for children and adults for both FVIII and FIX. Discussion: This was the first study to report large scale data on PWH switching from SHL to EHL concentrates. The results show that although an increased THL was observed at a group level, this was not the case for all individual patients. THL was extended by less than 20% after switching in 27% of patients with haemophilia A, with an actual decrease in THL in 9.9%. THL was extended by a minimum of 25% in patients with haemophilia B. This seems to support the use of individualized PK assessment in patients with haemophilia to guide clinical decisions on switching from SHL to EHL concentrates. Disclosures Versloot: Bayer: Research Funding. Germini:Bayer: Research Funding; NovoNordisk: Research Funding; Roche: Research Funding; Takeda: Research Funding. Iorio:Freeline: Research Funding; Pfizer: Research Funding; NovoNordisk: Research Funding; CSL: Research Funding; BioMarin: Research Funding; Octapharma: Research Funding; Takeda: Research Funding; Uniqure: Research Funding; Grifols: Research Funding; Roche: Research Funding; Bayer: Research Funding; Sanofi: Research Funding; Spark: Research Funding. Fischer:Bayer, Biogen, Pfizer, Baxter/Shire, and Novo Nordisk: Research Funding; Bayer, Baxter/Shire, SOBI/Biogen, CSL Behring, Octapharma, Pfizer, NovoNordisk: Research Funding; Bayer, Baxter, Biogen, CSL Behring, Freeline, Novo Nordisk, Pfizer, Roche, and Sobi: Consultancy.