Idiopathic non-mast cell angioedema: Treatment insights from global experts

Background: Idiopathic non-mast cell angioedema (INMA) is a rare disease typified by recurrent attacks of cutaneous and subcutaneous swelling. Every attack carries the potential for severe morbidity and, in the case of laryngeal involvement, mortality. Whereas therapies approved for hereditary angioedema (HAE) have been used in the care of patients with INMA, little is known with regard to their efficacy for the treatment of this disease. Objective: The objective was to gather evidence from global experts, ranking their assessment of on-demand therapy (ODT) and long-term prophylactic (LTP) treatment efficacy for INMA. Methods: A survey was developed and distributed to international experts invited to attend a 2023 symposium. INMA was diagnosed by standardized criteria. Linkert scales were used to rate the efficacy for ODT and LTP therapy. Enrollment was closed after 1 month and the data were analyzed. Results: Surveys were distributed to 31 experts from 16 countries with a 77% response rate (n = 24) reporting on 300 patients with INMA. Efficacy rankings of ODT were the following: icatibant (14 experts with 93 treated patients), 46.2% high and 38.7% moderate; and plasma-derived C1 inhibitor (C1INH) (13 experts with 31 treated patients), 32.3% moderate and 45.2% mild. Efficacy rankings of LTP were the following: antifibrinolytics (11 experts with 52 treated patients), 23.1% high and 38.5% moderate; lanadelumab (5 experts with 19 treated patients), 21% high and 79% moderate; and subcutaneous C1INH (3 experts with 19 treated patients), 21.1% moderate and 79.0% mild. LTP efficacy was also recorded for berotralstat and progestin. Conclusion: Icatibant (ODT) and either antifibrinolytics or lanadelumab (LTP) were ranked as the most efficacious treatments for the patients with INMA (among medications with at least five treated patients) by the expert physicians. Progestins, berotralstat, and plasma derived C1INH each demonstrated a favorable prophylactic effect; however, broader experience will be required to formulate overall recommendations.