Registry‐based analysis of Icatibant and C1‐inhibitor use in treatment of laryngeal attacks of hereditary angioedema

To the editor, Hereditary angioedema (HAE) is a rare condition which manifests as repeated episodes of localized subcutaneous or submucosal oedema.1 Oedemas involving the upper airways carry the risk of asphyxiation and death. The aim of this study was to present our clinical experience of icatibant and C1 inhibitor use for treating HAE1/2 laryngeal attacks (LA). To our knowledge, this is the first direct comparison of these treatment approaches for LA. A retrospective patient record analysis was performed. Data were collected from the Czech national registry of primary immunodeficiencies, where all known diagnosed HAE patients in Czechia are registered. Data collected between March 2012 and December 2019 were analysed. The attacks were recorded on paper diaries and reported by e-mail, then validated by attending doctors during patients' visits and entered electronically in the registry. Repeated dose/therapy was defined as using the same or another drug within 48 h after the first treatment. Generalized estimating equation (GEE) was used to evaluate differences between treatments with adjustment for potential dependencies among time courses of LA from one individual. Attacks that had missing data on the modelled time courses were excluded from the individual analysis. All analyses were conducted using R version 4.0.4 R Core Team (2021). 2 Data from 180 HAE patients (153 HAE1; 26 HAE2; and 1 HAEnC1INH) were available. A total of 5690 attacks were recorded in 153 patients, of which 499 (8.8%) were laryngeal attacks, occurring in 66 patients (40 females and 26 males; 54 HAE1 and 12 HAE2). Another attack location was present in 217 LA, median age at LA was 43.2 (range 5.0– 74.7) years, and triggers were identified in 24.4% of LA (Table 1). Almost all LA (497, 99.6%) were actively treated. Drug use was not randomized but was influenced by patient preference and HAE centre experience. Most attacks, 345 (69.4%), were treated with icatibant (Firazyr®), 94 (18.9%) attacks with recombinant human C1INH (rhC1 INH, Ruconest®), 52 (10.5%) attacks with plasmaderived, pasteurized, nanofiltered C1INH (pnfC1INH, Berinert®) and 2 (0.4%) attacks with plasmaderived, nanofiltered C1INH (nfC1INH, Cynrize®). Because only 2 LA were treated with nfC1INH, the data were not analysed. Three attacks were treated with attenuated androgens and one with fresh frozen plasma, which were also excluded from analysis. In our study, fixed drug doses were used Firazyr® (30 mg), Ruconest® 2100 U 1– 2 vials (median dose 2100 U, range 2100– 4200 U) and Berinert® 500 IU 1– 2 vials (median dose 1000 IU, range 500– 1000 IU). Fortythree patients (65%) with a LA were on longterm prophylaxis (LTP) at the time of the attacks. Two hundred seven (41.6%) LA occurred despite LTP with C1INH (rhC1INH 34 attacks in 2 patients, pnfC1INH 31 attacks in 4 patients), attenuated androgens (119 attacks in 37 patients) and tranexamic acid (58 attacks in 37 patients). In 35 attacks, the patients had been using combined LTP with attenuated androgens and tranexamic acid. This means that 68.6% LA occurred in people taking LTP with attenuated androgens and tranexamic acid, but only 16.4% LA occurred in those using LTP with pnfC1INH and 15% with rhC1INH. Treatment had to be repeated in 71 LA (14.3%), but less frequently in those LA where no other site was affected (6.8%). An adverse reaction associated with the LA treatment was reported in 1 (0.2%) attack. This adverse reaction was evaluated as vasovagal syncope. LA treatment was evaluated as effective in 98.4% of attacks.