132 Chapter 7 Figure 3. Plasma concentrations of emicizumab according to the time since starting emicizumab with adherence. The subgroup analyses on the last observed concentration per individual in the maintenance phase demonstrated a significant difference in the adherence subgroups: non-adherent individuals (n = 6) had a median concentration of 18 (IQR 8−30) µg/mL, while adherent individuals (n = 88) had a median concentration of 63 (IQR 51−80) µg/mL (p-value <0.001), which included eight individuals (9%) with last concentrations of <40 µg/mL. Therefore, the concentrations from non-adherent individuals were excluded from further analyses of the age, dosing interval and BMI subgroups. The adults/adolescents had median concentrations of 69 (IQR 51−87) µg/mL, while the children had median concentrations of 58 (IQR 51−66) µg/mL (p-value 0.017). The concentrations were similar across the dosing interval and BMI subgroups, as presented in Supplemental Table ST3. Bleeds The data on treated bleeds with an overall follow-up in of 131 person-years before and 96 person-years during the emicizumab therapy are summarized in Table 2. The total number of treated bleeds observed decreased from 442 before to 74 during the emicizumab therapy, with a concomitant significant reduction of ABRs from 3.6 (95% CI 2.9–4.4), to 0.8 (95% CI 0.6–1.1) (p-value <0.001). The number of treated joint bleeds decreased from 271 before to 34 during the emicizumab therapy, with a concomitant significant reduction of AJBRs from 2.2 (95% CI 1.7–2.7) to 0.4 (95% CI 0.2–0.6) (p-value <0.001). The number of treated muscle bleeds decreased from 72 before to 13 during the emicizumab therapy. As presented in Table 2, the bleed rates before emicizumab were higher in adults/adolescents than in children. Concomitantly, the reduction in bleed rates after switching to emicizumab therapy appeared more pronounced in adults (ABR 80%, AJBR 86%) than in children (ABR 70%, AJBR 50%).