Update on the Use of C1-Esterase Inhibitor Replacement Therapy in the Acute and Prophylactic Treatment of Hereditary Angioedema

• Published in: Clinical reviews in allergy & immunology 2019-04, Vol.56 (2), p.207-218
• Main Authors: Henry Li, H., Riedl, Marc, Kashkin, Jay
• Format: Article
• Language: English
• Subjects: Activities of daily living; Acute Disease; Adolescents; Age Factors; Allergology; Angioedema; Angioneurotic edema; Asthma; Bradykinin; Children; Competition (Economics); Complement C1 Inhibitor Protein - administration & dosage; Complement C1 Inhibitor Protein - adverse effects; Complement C1 Inhibitor Protein - therapeutic use; Disease prevention; Disease Progression; Drug therapy; Edema; Enzymes; Esterase; Formulations; Guidelines; Health Care Costs; Hereditary Angioedema Types I and II - drug therapy; Hereditary Angioedema Types I and II - prevention & control; Humans; Hydrolases; Immunology; Internal Medicine; Intravenous administration; Medical treatment; Medicine; Medicine & Public Health; Patients; Permeability; Plasma; Practice Guidelines as Topic; Premedication; Preventive medicine; Pricing; Prophylaxis; Proteins; Rare diseases; Recombinant Proteins - administration & dosage; Recombinant Proteins - adverse effects; Recombinant Proteins - therapeutic use; Self-administration; Time Factors; Treatment Outcome; Youth
• ISSN: 1080-0549; 1559-0267
• DOI: 10.1007/s12016-018-8684-1

In the vast majority of patients with hereditary angioedema (HAE), angioedema attacks are due to the quantitative or functional deficiency of C1-esterase inhibitor (C1-INH), which leads to increased vascular permeability and unregulated release of bradykinin. Exogenous administration of C1-INH is a rational way to restore the concentration and functional activity of this protein, regulate the release of bradykinin, and attenuate or prevent subcutaneous and submucosal edema associated with HAE. Recent international guidelines for the management of HAE include C1-INH as an option for acute treatment of HAE. In addition, these guidelines recommend C1-INH as first-line treatment for long-term prophylaxis and as the therapy of choice for short-term/preprocedural prophylaxis. Several C1-INH products are available, with approved indications varying across regions. For the acute treatment of HAE, both plasma-derived and recombinant C1-INH formulations have been shown to be effective and well tolerated in adolescents and adults with HAE, with onset of relief within 30 min to a few hours. Plasma-derived C1-INH is approved for use in children, and recombinant C1-INH is being evaluated in this population. Intravenous (IV) and subcutaneous (SC) formulations of C1-INH have been approved for routine prophylaxis to prevent HAE attacks in adolescents and adults. Both formulations when administered twice weekly have been shown to reduce the frequency and severity of HAE attacks. The SC formulation of C1-INH obviates the need for repeated venous access and may facilitate self-administration of HAE prophylaxis at home, as recommended in HAE treatment guidelines. As with most rare diseases, the costs of HAE treatment are high; however, the development of additional acute and prophylactic medications for HAE may result in competitive pricing and help drive down the costs of HAE treatment.