Study design
All enrolled patients completed a four-week observation period, followed by an eight-week treatment period with rhC1-INH (Recombinant human C1 esterase inhibitor (rhC1-INH), Conestat alfa/Ruconest®; Pharming Technologies; Leiden , The Netherlands), followed by another four-week observation period (Supplemental figure 1). Throughout the entire trial, patients continued using 4dd antihistamines. The total dose of rhC1-INH was calculated based on body weight (50 IU/kg; max 4200 IU) and was twice-weekly administered intravenously over a time course of five minutes.
A detailed medical history and physical examination were recorded at first visit and adverse events and concomitant drug use were registered at each following visit.
The attack frequency and severity were recorded in the AE activity score (AAS) form.19 Weekly AAS results (AAS7) were combined into AAS scores per four weeks (AAS28). An attack was separated from a subsequent attack when there had been an AE free period between reported swellings on subsequent days as scored on the AAS form. The AE Quality of Life score (AE-QoL) was used to assess the effect of AE on quality of life,20 with 0 to 23 indicating “no effect”, 24 to 38 indicating a “small effect” and ≥ 39 indicating a “moderate to large effect”.21 The primary endpoint of the study was a reduction in attack frequency of 50% in the treatment period compared to the cumulative observation period. Secondary outcomes were AAS over 28 days (AAS28) and AE-QoL scores during the treatment period compared to observation period. Outcomes were assessed per case. Follow-up data was collected by analysing patient records.