The Impact on Quality of Life Following Treatment with Plasma Prekallikrein Targeted Oligonucleotide Antisense Therapy in Hereditary Angioedema Patients

Patients with hereditary angioedema (HAE) often experience emotional distress and reduced health-related quality of life (HRQoL). Improving quality of life has become an important hallmark of disease management of HAE. Selective inhibition of plasma prekallikrein by antisense oligonucleotide treatment (PKK-LRx) reduced angioedema attacks by more than 90% in a phase 2 trial. The impact of this treatment on HRQoL was a predefined end-point in this trial. In this phase 2 trial, patients with hereditary angioedema with C1-inhibitor deficiency (HAE type I or II) were randomly assigned in a 2:1 ratio to a 16-week treatment period with subcutaneous dosing of 80 mg PKK-LRx or placebo every four weeks. Quality of life was assessed with the validated angioedema quality of life questionnaire (AE-QoL) at randomization and the end of study. Scores range from 0 – to 100, with higher scores indicating greater impairment. The minimal clinically important difference is defined as a change of six points. A total of 20 patients with HAE were enrolled, of whom 14 received PKK-LRx and 6 placebo. Patients reported higher overall HRQoL over 17 weeks in the PKK-LRx treatment group compared with placebo. The mean change in total score of the AE-QoL in HAE patients treated with PKK-LRx was -26.85, compared with -6.15 in the placebo group (P=0.002). These reductions were also observed across all individual domains of the AE-QoL compared with placebo. HRQoL assessment revealed clinically meaningful and sustained improvements from baseline in overall quality of life and across all domains of the AE-QoL questionnaire.