Open-label use of Nanofiltered C1 Esterase Inhibitor (human) for Treatment or Prophylaxis of Acute Attacks of Hereditary Angioedema (HAE) in Pregnant Subjects

Introduction: Pregnancy has been associated with an increased number of HAE attacks. Attenuated androgens are often prescribed for prophylaxis of HAE attacks, but are contraindicated in pregnancy (Category X) due to the potential for adverse events including virilization of the female fetus. Presented here are reports of nf-C1 INH use in pregnant subjects from nf-C1 INH open-label studies.

Methods: Pregnancy was not an exclusion criterion in two open label studies investigating the use of nf-C1 INH for the treatment of acute attacks and for prophylaxis of HAE attacks. In these studies nf-C1 INH 1000 U IV was administered for either acute attacks (followed by another injection 60 minutes later if needed) or routine prophylaxis (every 3-7 days). Pregnancy outcome data were collected retrospectively. Approval was obtained from WIRB and informed consent obtained from all subjects.

Results: Fourteen pregnant women were treated with nf-C1 INH in the studies; one subject who was treated in both studies delivered a healthy neonate. Of the 13 remaining subjects, 3 subjects enrolled in the acute treatment study. One received 8 doses and 2 subjects received a single dose of nf-C1 INH at delivery only. All 3 subjects delivered healthy neonates. Ten subjects in the prophylaxis study received a median of 34 doses (range: 2 to 85) during their pregnancy and reported the following outcomes: 7 subjects delivered 8 healthy neonates (1 set of twins), 1 subject (45yr old) with a history of miscarriage and ectopic pregnancy had a spontaneous abortion (reported as possible ectopic pregnancy), and 1 subject delivered a stillborn neonate with multiple congenital anomalies. This subject was first exposed to nf-C1 INH in the second trimester. One subject had an unknown outcome.

Conclusion: In this limited sample of pregnant women, nf-C1 INH had a favorable risk/benefit profile for management of HAE.