76 Chapter 4 Figure 3. Boxplots comparing the relative differences of the determinant group with the non-determinant group. The ‘+’ illustrates the mean. Boxplot 3A, determinant is anti-FVIII antibodies ≥0.6 BU/mL with a mean relative difference 133% (95% CI 81, 185%). Boxplot 3B, determinant is the exposed group compared to unexposed group with a mean relative difference -37% (95% CI -65, -9%). Also, specific FVIII product subgroups were compared to the unexposed group. Plasmaderived FVIII product (n = 7) had a relative difference of -64% (95% CI: -114; -15%). The two B-domain modified products included in this study were turoctocog alfa (NovoEight® n = 22) and efmoroctocog alfa (Elocta® n = 5). The relative differences of samples with B-domain modified products (n = 27) were -58% (95% CI: -89; -26%) lower compared to the relative differences in the unexposed group. Linear regression was also performed on turoctocog alfa and efmoroctocog alfa separately and significantly demonstrated their relative differences were -53% (95% CI: -86; -20%) and -77% (95% CI: -136; -17%) lower when compared to the relative differences of the unexposed samples. In general, all exogenous FVIII products resulted in negative relative differences (Table 2), meaning that the FVIII plasma concentration is lower compared to the FVIII activity. No significant differences were found for age, body weight, the subgroup full-length FVIII products (n = 32), octocog alfa (recombinant full-length FVIII: Advate® n = 8; Helixate®/ Kogenate® n = 18), co-medications desmopressin (n = 6), heparin and low molecular weight heparins (n = 16), tranexamic acid (n = 10), and co-morbidities heart disease (n = 6) or hepatitis B and C (n = 19). The determinants gender, other co-medications (such as oral anticoagulants, antiplatelet drugs, immunosuppressive drugs, and corticosteroids), and other co-morbidities (such as HIV, lung disease, hypertension) could not be studied because of low variability and numbers.
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