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

COMPACT Investigators

Research output: Contribution to journalArticle

3 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1793-1802.e2
JournalJournal of Allergy and Clinical Immunology: In Practice
Volume7
Issue number6
DOIs
StatePublished - Jul 1 2019

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Hereditary Angioedemas
Angioedema
Therapeutics
Complement C1 Inhibitor Protein
Safety
Incidence

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy

Cite this

@article{be8b2c0b551c4a939ec267d7d442f5db,
title = "Long-Term Outcomes with Subcutaneous C1-Inhibitor Replacement Therapy for Prevention of Hereditary Angioedema Attacks",
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.",
author = "{COMPACT Investigators} and Timothy Craig and B. Zuraw and Hilary Longhurst and M. Cicardi and Konrad Bork and C. Grattan and Constance Katelaris and Gordon Sussman and Keith, {Paul K.} and William Yang and Jacques H{\'e}bert and Jana Hanzlikova and P. Staubach-Renz and Inmaculada Martinez-Saguer and Markus Magerl and Emel Ayg{\"o}ren-P{\"u}rs{\"u}n and Henriette Farkas and A. Reshef and Shmuel Kivity and Sergio Neri and I. Crisan and Teresa Caballero and Baeza, {Maria L.} and Hernandez, {Maria Dolores} and H. Li and William Lumry and Bernstein, {Jonathan A.} and Iftikar Hussain and John Anderson and Schwartz, {Lawrence B.} and Joshua Jacobs and Michael Manning and Donald Levy and Marc Riedl and Sandra Christiansen and Henrike Feuersenger and Ingo Pragst and S. Mycroft and D. Pawaskar and Iris Jacobs",
year = "2019",
month = "7",
day = "1",
doi = "10.1016/j.jaip.2019.01.054",
language = "English (US)",
volume = "7",
pages = "1793--1802.e2",
journal = "Journal of Allergy and Clinical Immunology: In Practice",
issn = "2213-2198",
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Long-Term Outcomes with Subcutaneous C1-Inhibitor Replacement Therapy for Prevention of Hereditary Angioedema Attacks. / COMPACT Investigators.

In: Journal of Allergy and Clinical Immunology: In Practice, Vol. 7, No. 6, 01.07.2019, p. 1793-1802.e2.

Research output: Contribution to journalArticle

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

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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DO - 10.1016/j.jaip.2019.01.054

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