Open Access

Timothy Craig, Bruce Zuraw, Hilary Longhurst, Marco Cicardi, Konrad Bork, Clive Grattan, Constance Katelaris, Gordon Sussman, Paul K. Keith, William Yang, Jacques Hébert, Jana Hanzlikova, Petra Staubach-Renz, Inmaculada Martinez Saguer, Markus Magerl, Emel Aygören-Pürsün, Henriette Farkas, Avner Reshef, Shmuel Kivity, Sergio Neri, Ioana Crișan, Teresa Caballero, María Luisa Baeza, Maria Dolores Hernandez, Henry Li, William Lumry, Jonathan A. Bernstein, Iftikar Hussain, John Anderson, Lawrence B. Schwartz, Joshua Jacobs, Michael Manning, Donald Levy, Marc A. Riedl, Sandra Christiansen, Henrike Feuersenger, Ingo Pragst, Sarah Mycroft, Dipti Pawaskar, Iris Jacobs

• 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 COMPACT trial. Objective: To assess the long-term safety, occurrence of angioedema attacks, and use of rescue medication with C1-INH(SC). Methods: Open-label, randomised, parallel-arm extension of COMPACT across 11 countries. Patients with frequent angioedema attacks, either study treatment-naïve or who had completed the COMPACT trial, were randomly assigned (1:1) to 40 IU/kg or 60 IU/kg C1-INH(SC) twice per week, with conditional up-titration to optimise prophylaxis. ClinicalTrials.gov registration: NCT02316353. Results: 126 patients with a monthly attack rate of 4.3 in 3 months prior to entry in the COMPACT program were enrolled and treated for a mean of 1·5 years; 44 patients (34·9%) had >2 years exposure. Median steady-state C1-INH functional activity increased to a maximum of 73.0% 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 annualised 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 >2 years, 19 (83%) were attack-free during months 25–30 of treatment. Conclusion: 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.