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Clinical Trial
. 2019 Jul-Aug;7(6):1793-1802.e2.
doi: 10.1016/j.jaip.2019.01.054. Epub 2019 Feb 15.

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

Timothy Craig  1 , Bruce Zuraw  2 , Hilary Longhurst  3 , Marco Cicardi  4 , Konrad Bork  5 , Clive Grattan  6 , Constance Katelaris  7 , Gordon Sussman  8 , Paul K Keith  9 , William Yang  10 , Jacques Hébert  11 , Jana Hanzlikova  12 , Petra Staubach-Renz  13 , Inmaculada Martinez-Saguer  14 , Markus Magerl  15 , Emel Aygören-Pürsün  16 , Henriette Farkas  17 , Avner Reshef  18 , Shmuel Kivity  19 , Sergio Neri  20 , Ioana Crisan  21 , Teresa Caballero  22 , Maria L Baeza  23 , Maria Dolores Hernandez  24 , Henry Li  25 , William Lumry  26 , Jonathan A Bernstein  27 , Iftikar Hussain  28 , John Anderson  29 , Lawrence B Schwartz  30 , Joshua Jacobs  31 , Michael Manning  32 , Donald Levy  33 , Marc Riedl  34 , Sandra Christiansen  34 , Henrike Feuersenger  35 , Ingo Pragst  35 , Sarah Mycroft  36 , Dipti Pawaskar  36 , Iris Jacobs  36 ; COMPACT Investigators
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Free article
Clinical Trial

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

Timothy Craig et al. J Allergy Clin Immunol Pract. 2019 Jul-Aug.
Free article

Abstract

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.

Keywords: C1-esterase inhibitor; HAEGARDA; Hereditary angioedema; Long-term; Prophylaxis; Safety; Subcutaneous.

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