A clinical evaluation of patients with known mutations (plasminogen and factor XII) with a focus on prophylactic treatment

Abstract

Background

Hereditary angioedema with normal C1-inhibitor (HAE-nC1-INH) is a rare genetic disease. The symptoms can resemble other forms of hereditary angioedema (HAE), but the specific laboratory values are inconspicuous. The knowledge about treatment strategies in HAE-nC1-INH remains insufficient; most of the drugs are only licensed and approved for other types of HAE.

Methods

An analysis of all patients with HAE-nC1-INH was carried out in a certified angioedema treatment center in southern Germany. Only patients with a confirmed HAE-nC1-INH mutation were included. The impact of disease was monitored with validated questionnaires.

Results

Eighteen patients were included: two families with a factor XII mutation and seven families with a plasminogen mutation. All individuals received icatibant for on-demand therapy—efficient treatment response was reported. Three patients were severely affected, and prophylaxis was initiated with lanadelumab. According to the questionnaires, the clinical course and symptoms improved significantly under this prophylactic regime.

Conclusion

This is one of the first descriptions of the clinical outcomes as a response to prophylactic treatment with lanadelumab in HAE-nC1-INH patients with a known mutation. The therapeutic management of HAE-1 and HAE-2 should also be the basis of HAE-nC1-INH, including prophylaxis.

Keywords:

• Hereditary angioedema
• HAE-nC1-INH
• C1-inhibitor
• prophylaxis
• treatment
• mutation
• plasminogen
• factor XII

Acknowledgment

The authors thank cand. med. Hannah Ramanathan for editorial assistance with regard to proper English language.

Ethical approval

This study protocol was reviewed and approved by the local ethics committee (Ethikkommission der Universität Ulm), approval number: 299/22.

Disclosure statement

R. Lochbaum has received funding to attend conferences/educational events from CSL Behring, BioCryst and Takeda. He has participated as an investigator in a clinical trial for Takeda and Pharvaris and received financial support for research projects from Takeda.

S. Trainotti has received grant research support and/or speaker/consultancy fees from CSL Behring and Takeda. She has also received funding to attend conferences/educational events from CSL Behring and Takeda. She has participated as an investigator in a clinical trial/registry for CSL Behring, BioCryst, IONIS Pharmaceuticals and Takeda.

J. Hahn has received speaker/consultancy fees from CSL Behring and Takeda. She has also received funding to attend conferences/educational events from CSL Behring and Takeda. She has participated as an investigator in a clinical trial/registry for CSL Behring, BioCryst, Pharvaris and Takeda.

J. Greve has received speaker/consultancy fees from CSL Behring, Kalvista Takeda and BioCryst. He has also received funding to attend conferences/educational events from CSL Behring and Takeda. He has participated as an investigator in a clinical trial/registry for CSL Behring, Pharvaris, BioCryst and Takeda.

T. K. Hoffmann has no conflict of interest to declare regarding this publication.

Additional information

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.