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

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.