D2.77 - Lanadelumab in C1-Esterase Inhibitor Non-Responding patient: A Case Report

Background: Hereditary angioedema (HAE) due to C1-esterase inhibitor deficiency is a rare but life-threatening genetic condition characterized by recurrent, non-pitting edema of the skin and mucous membranes. In many regions, patients face significant diagnostic delays and limited access to targeted therapies. This report describes a complex clinical case of a patient with a long history of undiagnosed HAE and a severe family history, who demonstrated poor response to standard plasma-derived C1-inhibitor prophylaxis but achieved remarkable improvement after switching to a monoclonal antibody targeting plasma kallikrein.

Methods: We analyzed the medical history, diagnostic process, and therapeutic outcomes of a female patient currently treated at a specialized allergy center in Kazakhstan. Disease control and quality of life were assessed using the Angioedema Control Test (AECT) and the Angioedema Quality of Life (AE-QOL) questionnaire. The clinical evaluation included laboratory confirmation of HAE Type I via low C4 levels and decreased C1-esterase inhibitor (C1-INH) antigen and functional levels.

Results: The patient experienced recurrent swelling since the age of 10; however, the diagnosis remained unrecognized for decades. Her family history was notable for the premature death of her mother at age 40 due to asphyxiation during an acute laryngeal edema. The definitive diagnosis of HAE Type I was finally established in 2020. In 2023, the patient commenced long-term prophylaxis with plasma-derived C1-inhibitor administered twice weekly. Despite this intervention, she continued to suffer from frequent and severe relapses, indicating a failure of standard replacement therapy. In 2025, the treatment regimen was transitioned to lanadelumab. Following the initiation of this kallikrein inhibitor, the frequency and severity of angioedema episodes were significantly reduced. The patient reported a dramatic improvement in her AECT scores and a substantial decrease in AE-QOL impairment, achieving stable disease remission for the first time.

Conclusions: This case underscores the challenges of managing HAE and the critical importance of early diagnosis and family screening. It demonstrates that when traditional C1-inhibitor prophylaxis fails to provide adequate control, switching to modern targeted therapies like lanadelumab can effectively prevent life-threatening attacks and restore the patient’s quality of life.