A safety review of prophylaxis drugs for adolescent patients with hereditary angioedema

ABSTRACT

Introduction

Hereditary angioedema (HAE) is characterized by recurrent subcutaneously and/or submucosally localized edematous swellings. The first symptoms often appear in childhood, and they may become more frequent and severe in puberty. Since the appearance of HAE attacks is unpredictable regarding the localization and the frequency, the attacks put a significant burden on the patients and crucially impacts their quality of life.

Areas covered

This review article analyzes the safety data acquired from the clinical trials conducted with the currently available medicinal products for the prophylactic treatment of hereditary angioedema due to C1 inhibitor deficiency and the safety data of observatory studies based on clinical practice. A review of the published literature was conducted using the PubMed database, clinical trials from ClinicalTrials.gov, and abstracts published at scientific conferences.

Expert opinion

The currently available therapeutic products have a good safety and efficiency profile and the international guidelines recommend them as first-line treatments. The choice should be made based on the evaluation of the availability and the preference of the patient.

KEYWORDS:

• Adolescent
• bradykinin
• children
• clinical trial
• hereditary angioedema
• prophylaxis
• safety
• treatment

Article highlights

• Hereditary angioedema with C1-inhibitor (C1-INH) deficiency (C1-INH-HAE) is a rare, autosomal dominant inherited disease, characterized by recurrent edematous episodes (HAE attacks).

• HAE attacks can occur at any age; in adolescence, an increase in the frequency of the symptoms may be observed, so this patient group requires great attention.

• C1-INH-HAE is a bradykinin mediated disorder, so HAE attacks do not respond to conventional treatment, they require a special therapy.

• Part of the targeted treatments act by inhibiting the development of bradykinin, and part of them block the effect of bradykinin on its receptor.

• The aim of the therapeutic strategy is the prevention or treatment of the ongoing HAE attack.

• Targeted prophylactic therapies are directed at the supplementation of deficient C1-INH and the inhibition of kallikrein.

• This review summarizes the experiences related to medications, with particular attention to their safety, currently available for the prophylactic treatment of the adolescent patient group.

Declaration of Interest

H Farkas received research grants from CSL Behring, Takeda and Pharming and served as an advisor for these companies and Kalvista and Biocryst, and has participated in clinical trials/registries for BioCryst, CSL Behring, Pharming, Kalvista, Pharvaris and Takeda. Z Balla has participated in clinical trials of CSL Behring, Pharvaris and Takeda. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Author contribution statement

The authors confirm contribution to the paper as follows: study conception and design: H Farkas, Z Balla,; data collection: Z Balla; analysis and interpretation of results: H Farkas, Z Balla. Author; draft manuscript preparation: H Farkas, Z Balla. All authors critically reviewed the results, revised the paper for intellectual content, provided detailed feedback, read and approved the final version of the manuscript.

Additional information

Funding

This paper was not funded.