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

H Henry Li,Marc Riedl,Jay Kashkin

doi:10.1007/s12016-018-8684-1

Abstract

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.

Highlights

Hereditary angioedema (HAE) is an autosomal dominant genetic disorder resulting from mutations in the SERPING1 gene that give rise to a deficiency in the quantity or function of endogenous C1-esterase inhibitor (C1-INH)
C1-INH is the primary regulator of the contact system, where it inhibits the activity of factor XIIa and plasma kallikrein, two enzymes that regulate the formation of bradykinin (Fig. 1)
Under conditions of C1INH deficiency, uncontrolled activation of the contact system leads to overproduction of bradykinin, a potent vasoactive peptide thought to be the primary mediator of angioedema in HAE

Summary

Introduction

Hereditary angioedema (HAE) is an autosomal dominant genetic disorder resulting from mutations in the SERPING1 gene that give rise to a deficiency in the quantity or function of endogenous C1-esterase inhibitor (C1-INH). Choosing and implementing the optimal treatment for an individual patient remains a challenge for physicians To address these challenges, a number of consensus recommendations and guidelines for HAE management have been published, including guidelines recently issued jointly by the World Allergy Organization (WAO) and the European Academy of Allergy and Clinical Immunology (EAACI) [7–10]. A number of consensus recommendations and guidelines for HAE management have been published, including guidelines recently issued jointly by the World Allergy Organization (WAO) and the European Academy of Allergy and Clinical Immunology (EAACI) [7–10] All these consensus documents share the following principles: (1) HAE therapy needs to be individualized, (2) all patients should have access to acute (on-demand) treatment, and (3) some patients require long-term and shortterm prophylaxis (Table 1) [7–10].

Acute treatment plan should establish

Findings

Summary