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Long-term subcutaneous C1-inhibitor replacement is safe and effective for hereditary angioedema

Published online: February 14, 2019

Hereditary angioedema (HAE) is a rare genetic disorder secondary to the deficiency or dysfunction of the C1 inhibitor (C1-INH) protein. HAE is a debilitating disease characterized by painful, disfiguring, and potentially fatal attacks of swelling of the skin of the face and body and the tissues of the upper respiratory, gastrointestinal, and genitourinary tracts. Intravenous C1-INH replacement therapy is currently recommended as a first-line treatment of HAE and for the long-term prophylaxis of angioedema attacks. However, evidence from real-world clinical practice suggests that attacks can occur in approximately 50% of patients with HAE using the recommended dose of prophylactic intravenous C1-INH, and that they often require higher doses, adding to the overall cost of current prophylactic therapy. Recently, a highly concentrated human plasma–derived C1-INH for subcutaneous injection (C1-INH[SC]) was approved for long-term prophylaxis in patients with HAE after showing safety and efficacy in reducing the attack rate in the Clinical Study for Optimal Management of Preventing Angioedema with Low-Volume Subcutaneous C1-Inhibitor Replacement Therapy (COMPACT).

In a recent long-term study published in The Journal of Allergy and Clinical Immunology: In Practice, Craig et al. describe a multicenter, randomized, parallel-arm, open-label extension of phase 3 of COMPACT that aimed to determine the long-term safety of C1-INH(SC). The study enrolled a total of 126 patients with a mean age of 41 years, with ten patients younger than 18 years. Patients were randomly assigned to receive either 40 or 60 IU/kg of C1-INH(SC) twice per week during two different treatment periods: a 24-week fixed-dose period and a 28-week dose-adjustment period. A total of 23 patients (35%) received more than 2 years of exposure. Safety endpoints included serious adverse events (SAEs), adverse events (AEs) leading to premature discontinuation, and HAE attacks resulting in hospitalization.

The results from this study showed that both doses of C1-INH(SC) were well tolerated, and AEs were generally mild to moderate in intensity and resolved within 24 hours of appearance. The most commonly observed AEs were injection-site reactions, which were reported in about half of the patients at any time during the study. No treatment-related SAEs were reported in either arm. The median annualized attack rate was reduced from 30 attacks per year prior to the study to 1 attack per year during the study. More than 80% of patients treated with C1-INH(SC) 60 IU/kg for more than 2 years no longer required any rescue medication and achieved an attack-free status.

This long-term study confirms the results of the pivotal COMPACT study and demonstrates that long-term subcutaneous replacement therapy with C1-INH reduces HAE symptoms, the number of angioedema attacks, and the need for rescue medication. Furthermore, it offers a safe and sustained prophylactic effect, with the vast majority of patients becoming free from debilitating disease symptoms.

The Journal of Allergy and Clinical Immunology: In Practice is an official journal of the AAAAI, focusing on practical information for the practicing clinician.