134 Chapter 7 To allow comparison with previous reports, the proportion of individuals without (joint) bleeds during emicizumab were calculated in 24-week intervals. A total of 78 PwHA had a follow-up time of ≥24 weeks after starting emicizumab therapy (i.e., the first 24-week interval), of which the proportion without any bleeds was 73.1%; the proportion with 1−3 bleeds was 24.4%, and the proportion with >3 bleeds was 2.6% (see Supplemental Figure SF1). Ten of the total 32 bleeds (31%) in the first 24-week interval occurred during the loading phase. Only two individuals had >3 bleeds during this first 24-week interval: the first one had five bleeds during the loading phase and one during the maintenance phase, and the second individual had four bleeds during the maintenance phase. The zero-bleed proportion of all individuals was 75.0%, 73.3% and 80.0%, respectively, in the consecutive 24-week intervals. After the first 24-week interval, the proportion with >3 bleeds remained at 0% for all the consecutive 24-week intervals. Due to pain experienced during infusion of emicizumab, most children (n = 21, 66%) used a local anaesthetic cream (EMLA®) prior to the injection. Except for local pain, no adverse events of changes in the complete blood count and the renal function, nor thromboses or losses of response were observed. As presented in Figure 4, bleed rates (p-values 0.997 and 0.863) and joint bleed rates (p-values 0.354 and 0.148) were similar across the concentration subgroups of <40, 40−80 and >80 µg/mL. Additionally, similar bleed rates were observed across the adherence, age, dosing interval, BMI and FVIII inhibitors subgroups, which are presented in Supplemental Table ST3. Figure 4. The mean annualized bleed rates (ABRs) and annualized joint bleed rates (AJBRs) (95% CI) of only treated bleeds across the subgroups of the plasma concentration of emicizumab.