Improving the burden of hereditary angioedema through targeted treatment

Hereditary angioedema (HAE) is a rare autosomal dominant disease, which so far cannot be cured. The aim of this thesis is to describe the full burden of this disease and to contribute to new therapeutic strategies to prevent the recurrence of angioedema attacks. Part A concerns the entire burden of HAE, predominantly focussing on patients in the Netherlands. This burden of HAE comprises of angioedema control, health-related quality of life, the burden of treatment, personal and societal costs, reproductive decisions, precautionary measures before partaking in activities which can trigger angioedema attacks, and the burden that comes with participating in clinical trials. In Part B the current landscape of prophylactic and acute treatment is described, where after the prospective targets of future therapies are discussed. Part B contains the description of the first two angioedema patients who received prekallikrein antisense oligonucleotides, as well as the phase 2 trial with this new treatment in HAE patients. This is followed by additional laboratory analyses of plasma collected in this phase 2 trial, elucidating whether prekallikrein inhibition causes increased thrombotic risk. Lastly, the phase 2 trial investigating activated factor XII inhibition in HAE patients is discussed.