Anouk Donners

126 Chapter 7 MATERIALS AND METHODS Design and setting This single-center, retrospective observational study on prospectively registered data was conducted at the Van Creveldkliniek, University Medical Center in Utrecht, the Netherlands. All PwHA (adults and children) who started emicizumab between July 2018 and January 26th 2022 were eligible. The inclusion criteria were a diagnosis of congenital haemophilia A, at least one plasma emicizumab concentration measurement available and no objection against the usage of clinical data for research in the Electronic Health Record. The PwHA were switched from prophylaxis or on-demand therapy with either FVIII concentrates (standard half-life [SHL] or extended half-life [EHL]) or bypassing agents (BPA; i.e., activated factor VII [rFVIIa] or activated prothrombin concentrate complex [aPCC]) to emicizumab therapy during a regular medical visit. All PwHA received emicizumab loading doses of 3 mg/kg per week for 4 consecutive weeks according to the drug label. Subsequently, the maintenance dose (≥28 days after the first loading dose) was an equivalent of the registered dose of 6 mg/kg/4 weeks, but with varying dosing intervals that were rounded to the highest frequency and the nearest vial size [8, 9]. These dosing intervals ranged between 7 and 28 days and were based on shared decision-making between the PwHA and their own treating clinician. Previous prophylaxis was continued for 1 week during the emicizumab loading phase, except for individuals with inhibitors or frequent bleeding, who then continued their regular prophylaxis for 2 weeks after starting emicizumab. The PwHA were instructed to contact the center in case of suspected bleeds. Bleeding episodes were treated with regular doses of FVIII or rFVIIa. This study was evaluated and approved by the Medical Ethics Review Board of UMC Utrecht with study number 21/825. Individual informed consent was waived. Variable and outcome analyses The data sources were health diaries, telephone calls to attending clinicians and clinical visits. The data on outcomes and variables were prospectively registered in the Electronic Health Records and extracted by performing retrospective chart reviews. The data were collected preferably 1 year (but at least 12 weeks) before starting with emicizumab therapy until the study’s end date of January 26th, 2022 (see Figure 1 for a schematic study timeline per individual).