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

Abstract

Background: 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. Methods: 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. Results: 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. Conclusions: 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. Trial registration Clinicaltrials.gov identifier NCT02316353 (Registered December 10, 2014); https ://clini caltr ials.gov/ct2/ show/NCT02 31635 3.

Subcutaneous C1‐Inhibitor Concentrate for prophylaxis during pregnancy and lactation in a patient with C1‐INH‐HAE

“…As in our case, there were no reported congenital abnormalities 5 . Levy et al described four pregnant women with exposure to pdC1INH 40‐60 U/kg prophylaxis for four to 8 weeks during the COMPACT trial (Clinical Study for Optimal Management of Preventing Angioedema with Low‐Volume Subcutaneous C1‐Inhibitor Replacement Therapy) with a favorable pregnancy outcome 6 …”

Sugar Matters: Improving In Vivo Clearance Rate of Highly Glycosylated Recombinant Plasma Proteins for Therapeutic Use

“…HAE is characterized by recurrent episodes of severe swelling, which can result in life-threatening situations [ 5 , 19 ]. C1-INH administration on demand and as prophylaxis reduced the severity and the frequency of attacks, respectively [ 20 ]. Other examples of the efficacy of purified plasma proteins in diseases are plasma derived coagulation factors (factor VIII and factor IX) in haemophila [ 21 ] or gammaglobulins in primary and secondary humoral immunodeficiencies [ 22 ].…”

Reviewing clinical considerations and guideline recommendations of C1 inhibitor prophylaxis for hereditary angioedema

“…C1INH can be used across a range of patient groups, including children as young as 6 years old (United States) or "adolescents" (EU), and in women who are of childbearing age, pregnant, or lactating. 23,24,[57][58][59] Regarding use in the elderly, the US prescribing information notes that "clinical experience has not identified differences in responses between the elderly and younger patients," but recommends that dosing be initiated at the low end of the dosing range, since this population has the potential for decreased hepatic, renal, or cardiac function as well as potential for more concomitant disease and/or other drug therapy. 24 Finally, patients with HAE should be made aware of patient advocacy organizations, such as the HAE international (HAEi) and US HAEA, as these provide important sources of patient support and education about their disease and management options, including LTP.…”