Long-term efficacy and safety of subcutaneous C1-inhibitor in women with hereditary angioedema: subgroup analysis from an open-label extension of a phase 3 trial

• Published in: Allergy, asthma, and clinical immunology Vol. 16; no. 1; p. 8
• Main Authors: Levy, Donald S, Farkas, Henriette, Riedl, Marc A, Hsu, Florence Ida, Brooks, Joel P, Cicardi, Marco, Feuersenger, Henrike, Pragst, Ingo, Reshef, Avner
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 04.02.2020; BioMed Central; BMC
• Subjects: Age; Angioedema; Angioneurotic edema; Birth control; C1-inhibitor; Comparative analysis; Edema; Estrogen; Estrogens; FDA approval; Female; Females; Genetic disorders; HAEGARDA; Hereditary angioedema; Hormones; Infants; Labels; Male identity; Menstruation; Phenols (Class of compounds); Population; Pregnancy; Pregnant women; Product development; Prophylaxis; Puberty; Sex hormones; Tumor necrosis factor-TNF; Women; Womens health; United States > US; C1-inhibitor; Pregnancy; Women; Childbearing; Hereditary angioedema; HAEGARDA; Estrogen; Conception; Female
• ISSN: 1710-1484; 1710-1492; 1710-1492
• DOI: 10.1186/s13223-020-0409-3

Women with hereditary angioedema due to C1-inhibitor deficiency (HAE-C1INH) experience more frequent and severe angioedema attacks compared with men. Fluctuations in female sex hormones can influence HAE attack frequency and severity. Subcutaneous C1-INH (C1-INH [SC]) is indicated as routine prophylaxis to prevent HAE attacks. In this post hoc subgroup analysis, we evaluated the efficacy and safety of C1-INH (SC) in female subjects with HAE-C1INH enrolled in an open-label extension of the pivotal phase III COMPACT trial. In this multicenter, randomized, parallel-arm trial, eligible subjects (age ≥ 6 years with ≥ 4 attacks over 2 consecutive months) received C1-INH (SC) 40 IU/kg or 60 IU/kg twice weekly for 52 to 140 weeks. Analyses of efficacy endpoints were performed for all female subjects and those of childbearing age (age ≥ 15 to ≤ 45 years), including subjects who became pregnant during the evaluation period. Overall, 91% (69/76) of female subjects were classified as responders (≥ 50% reduction in HAE attacks relative to the pre-study period); 82% experienced < 1 attack/4 weeks. The median number of attacks/month was 0.10, with 96% median reduction in attacks relative to the pre-study period. Results were similar in the subgroup of subjects of childbearing age. Four women who became pregnant during the trial and were exposed to C1-INH (SC) during the first trimester delivered healthy babies with no congenital abnormalities. C1-INH (SC) prophylaxis was safe and effective in women with HAE-C1INH, including those of childbearing age. Four women exposed to C1-INH (SC) during the first trimester had uneventful pregnancies and delivered healthy babies. Clinicaltrials.gov identifier NCT02316353 (Registered December 10, 2014); https://clinicaltrials.gov/ct2/show/NCT02316353.