Anouk Donners

18 Chapter 1 Thesis objectives This thesis is designed to optimise the drug monitoring of FVIII and emicizumab in PwHA. To achieve this objective, I will: 1) Develop and validate the LC-MS/MS methods that quantify FVIII and emicizumab in human plasma; 2) investigate the dose–biomarker relationship of FVIII and the dose–concentration– response relationships of emicizumab; and 3) propose and evaluate a cost-efficient dosing strategy for emicizumab. Outline In Chapters 2, 3 and 5, I provide a framework for measuring therapeutic proteins, such as FVIII and emicizumab, in human plasma using LC-MS/MS bioanalysis. In Chapter 4, I investigate the concentration–biomarker relationship of FVIII, and in Chapters 5−7, I investigate the dose–concentration–response relationship for emicizumab. In Chapters 6−8, I conduct studies to support a cost-efficient approach to emicizumab treatment, which may inspire others to dose biopharmaceuticals more affordable. An overall discussion in Chapter 9 is presented in the last chapter of this thesis to put the lessons learned into a broader perspective. I also deliberate on the potential future applications of monitoring FVIII concentrations in PwHA and a framework for the cost-efficient dosing of biopharmaceuticals. This thesis can be summarised as the groundwork for measuring and monitoring FVIII and emicizumab with LC-MS/MS bioanalysis in PwHA. Author’s contribution AD conceived the idea and set-up the general introduction. AD conducted literature review, outlined and wrote the general introduction. Throughout the process, AD asked and implemented input and feedback from the supervision team.