TY - JOUR
T1 - Long-Term Outcomes with Subcutaneous C1-Inhibitor Replacement Therapy for Prevention of Hereditary Angioedema Attacks
AU - COMPACT Investigators
AU - Craig, Timothy
AU - Zuraw, B.
AU - Longhurst, Hilary
AU - Cicardi, M.
AU - Bork, Konrad
AU - Grattan, C.
AU - Katelaris, Constance
AU - Sussman, Gordon
AU - Keith, Paul K.
AU - Yang, William
AU - Hébert, Jacques
AU - Hanzlikova, Jana
AU - Staubach-Renz, P.
AU - Martinez-Saguer, Inmaculada
AU - Magerl, Markus
AU - Aygören-Pürsün, Emel
AU - Farkas, Henriette
AU - Reshef, A.
AU - Kivity, Shmuel
AU - Neri, Sergio
AU - Crisan, I.
AU - Caballero, Teresa
AU - Baeza, Maria L.
AU - Hernandez, Maria Dolores
AU - Li, H.
AU - Lumry, William
AU - Bernstein, Jonathan A.
AU - Hussain, Iftikar
AU - Anderson, John
AU - Schwartz, Lawrence B.
AU - Jacobs, Joshua
AU - Manning, Michael
AU - Levy, Donald
AU - Riedl, Marc
AU - Christiansen, Sandra
AU - Feuersenger, Henrike
AU - Pragst, Ingo
AU - Mycroft, S.
AU - Pawaskar, D.
AU - Jacobs, Iris
N1 - Publisher Copyright:
© 2019 The Authors
PY - 2019/7/1
Y1 - 2019/7/1
N2 - 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.
AB - 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.
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U2 - 10.1016/j.jaip.2019.01.054
DO - 10.1016/j.jaip.2019.01.054
M3 - Article
C2 - 30772477
AN - SCOPUS:85063112545
SN - 2213-2198
VL - 7
SP - 1793-1802.e2
JO - Journal of Allergy and Clinical Immunology: In Practice
JF - Journal of Allergy and Clinical Immunology: In Practice
IS - 6
ER -