Anouk Donners

17 General Introduction Knowledge gaps Measuring the concentrations of FVIII and emicizumab with LC-MS/MS has not been done before. This LC-MS/MS technique may be of interest to treating clinicians because of its many advantages in comparison to other assays. The potential role of bioanalysis with LC-MS/MS in haemophilia A is schematically presented in Figure 3. For FVIII, the dose, the FVIII activity and the bleed outcomes are well correlated, but the role of the FVIII concentration measured with LC-MS/MS in the dose–concentration–response relation is unknown. For emicizumab, no biomarker has yet been identified, and the entire dose–concentration–outcome relation, established in the pre-approval studies, is unclear. Bioanalysis with the LC-MS/MS technique could be applied to start filling these knowledge gaps and to further optimise the monitoring of FVIII and emicizumab in PwHA in the future. Two questions arise from these knowledge gaps: - How is the relationship between FVIII concentration and FVIII activity best described? - How low can we dose emicizumab without sacrificing the desired clinical response? Figure 3. Dose–concentration–response relationship with bioanalysis of FVIII and emicizumab in PwHA. 1