Long-Term Outcomes with Subcutaneous C1-Inhibitor Replacement Therapy for Prevention of Hereditary Angioedema Attacks

Background For the prevention of attacks of hereditary angioedema (HAE), the efficacy and safety of subcutaneous human C1-esterase inhibitor (C1-INH[SC]; HAEGARDA, CSL Behring) was established in the 16-week Clinical Study for Optimal Management of Preventing Angioedema with Low-Volume Subcutaneous C1-Inhibitor Replacement Therapy (COMPACT). Objective To assess the long-term safety, occurrence of angioedema attacks, and use of rescue medication with C1-INH(SC). Methods Open-label, randomized, parallel-arm extension of COMPACT across 11 countries. Patients with frequent angioedema attacks, either study treatment-naive or who had completed COMPACT, were randomly assigned (1:1) to 40 IU/kg or 60 IU/kg C1-INH(SC) twice per week, with conditional uptitration to optimize prophylaxis (ClinicalTrials.gov registration no. NCT02316353). Results A total of 126 patients with a monthly attack rate of 4.3 in 3 months before entry in COMPACT were enrolled and treated for a mean of 1.5 years; 44 patients (34.9%) had more than 2 years of exposure. Mean steady-state C1-INH functional activity increased to 66.6% with 60 IU/kg. Incidence of adverse events was low and similar in both dose groups (11.3 and 8.5 events per patient-year for 40 IU/kg and 60 IU/kg, respectively). For 40 IU/kg and 60 IU/kg, median annualized attack rates were 1.3 and 1.0, respectively, and median rescue medication use was 0.2 and 0.0 times per year, respectively. Of 23 patients receiving 60 IU/kg for more than 2 years, 19 (83%) were attack-free during months 25 to 30 of treatment. Conclusions In patients with frequent HAE attacks, long-term replacement therapy with C1-INH(SC) is safe and exhibits a substantial and sustained prophylactic effect, with the vast majority of patients becoming free from debilitating disease symptoms

Whose primaries? Grassroots’ views on candidate selection procedures

Opening-up processes of candidate selection is often viewed as a means for political parties to regain legitimacy, and perhaps more crucially, members and voters. Despite a widespread belief that citizens want more democracy, including within parties, little research has questioned what sort of opening-up is desired—e.g. open or closed primaries—if at all, and by what type of citizens. Using data of the 2014 PartiRep voter survey in Belgium, we examine the diversity of preferences regarding candidate selection, and the extent to which preferences for open or closed primaries relate to voters’ participation in party organisations. Given the diversification of party affiliation types, we operationalise participation through two distinct variables: the formal party membership status of the respondents, and their party activism. We show that both membership and activism influence individual preferences, and that their effects are in fact conditional upon each other. Findings also raise crucial issues regarding the consequences of the multiplication of affiliation modes, the motivations and direction of intra-party reforms, as well as feed the debate on their expected versus genuine consequences.SCOPUS: ar.jinfo:eu-repo/semantics/publishe