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.