C1-Esterase Inhibitor Concentrate for Acute Laryngeal Hereditary Angioedema (HAE) Attacks: Different Treatment Response Based on Dosing Regimen?

Abstract

For acute treatment of hereditary angioedema (HAE) attacks, international consensus guidelines recommend plasma-derived C1-inhibitor concentrate (pdC1-INH) both at fixed and body weight-adjusted doses. Since fast response to treatment with a single dose is paramount for potentially life-threatening laryngeal HAE attacks, we compared available efficacy data with different pdC1-INH dosing regimens. We performed an indirect, descriptive comparison of treatment response with pdC1-INH at fixed doses of 500 or 1000 IU and body weight-adjusted doses of 20 IU/kg, using data from clinical studies with 1000 IU Cinryze®, and 500 or 1000 IU and 20 IU/kg Berinert®. Data were compared descriptively, using a Kaplan-Meier analysis, and by a Wilcoxon test. Median time to onset of symptom relief (95% confidence interval [CI]) was 15 minutes (14; 25) with 20 IU/kg Berinert (N=48), 30 minutes (30; 40) with 500 IU Berinert (N=48), 40 minutes (40; 40) with 1000 IU Berinert (N=145), and 45 minutes (30; 75) with 1000 IU Cinryze (N=82) (per-attack analysis). A similar difference was seen in a per-patient analysis, with significantly shorter median average time to onset of symptom relief with 20 IU/kg compared with fixed pdC1-INH doses (26 versus 43 minutes; p=0.019). No re-dosing was needed with body weight-adjusted dosing, while a second dose was used in up to 62% of attacks treated with 1000 IU. Available data suggest body weight-adjusted dosing with pdC1-INH at 20 IU/kg as preferred treatment choice over fixed dosing to ensure optimal treatment response for acute laryngeal HAE attacks.