Anouk Donners

127 Entire-vial dosing of emicizumab Figure 1. Schematic study timeline per individual. Baseline characteristics The following baseline characteristics were collected: haemophilia A severity, FVIII inhibitor status, age, weight, Body Mass Index (BMI), previous factor-replacement regimen and emicizumab regimen. The haemophilia severity was classified on endogenous FVIII activity as severe (<1%), moderate (1–5%), or mild (>5–40%) [10]. The FVIII inhibitor status was classified as present if the inhibitor titre at baseline was ≥0.3 BU/mL. All maintenance doses of emicizumab were converted to a 4-week dosing frequency for comparison (i.e., each mg/kg dose was divided by the dosing interval and multiplied by 28 days). Plasma concentrations of emicizumab According to the local protocol, plasma samples for emicizumab concentration measurements were usually assessed before the 4th loading dose (i.e., after receiving 3 loading doses), at 3 and 12 months after starting emicizumab and at least once a year thereafter. All concentrations were combined with monitoring of complete blood count and renal function. A (cross-)validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was used to quantify the concentration of emicizumab in human plasma [11, 12]. The plasma concentration-time curve was fitted using a weighted nonlinear least squares regression with a one-phase association model, and the fit was presented with 90%-prediction bands of points. The between- and within-individual variabilities of plasma emicizumab concentrations during the maintenance phase (defined from ≥28 days) were expressed as the percentage coefficient of variation (%CV), which was calculated as (SD/mean) × 100%. The within-individual variability was calculated for both ≥2 and ≥3 concentrations per individual without dose changes during the studied period. Bleeds The PwHA were monitored closely over time and it was mandatory to contact a 24/7-available attending clinician at any suspicion of bleeding. During those calls or visits, the need for FVIII/BPA treatment was evaluated and all cases of suspected joint- or muscle bleeds were evaluated at the clinic. Adverse events (e.g., thrombotic) were 7