Ruconest (recombinant C1-inhibitor, rhC1-INH) and Firazyr (icatibant) are safe and effective approaches as first-line treatment for hereditary angioedema (HAE) attacks in pregnant women, a study suggests.
Findings of the study, “Treatment of Hereditary Angioedema Attacks with Icatibant and Recombinant C1 Inhibitor During Pregnancy,” were published in the Journal of Clinical Immunology.
HAE is a rare genetic disorder characterized by sudden and recurrent episodes of swelling in the deeper layers of the skin, the upper airway, and the gastrointestinal (GI) tract. The disease is caused by genetic mutations in the SERPING1 gene, leading to lower levels of C1-inhibitor, in the case of HAE type 1, or to a dysfunctional C1-inhibitor whose levels remain normal or elevated in the case of HAE type 2.
Pregnancy can have different effects on HAE flare-ups, ranging from easing symptoms to aggravating the disease. Based on previous data from retrospective, observational, and case report studies, plasma-derived human C1-inhibitor concentrate (pdC1-INH) has been recommended as a course of treatment for acute attacks or as a short-term preventive treatment for pregnant women.
However, no studies until now have addressed the safety and efficacy of other treatments, including Firazyr, Kalbitor (ecallantide), or Ruconest, during pregnancy.
So researchers set out to document the clinical outcomes of six women — three with HAE type 1 and three with type 2 — who experienced acute HAE flare-ups during pregnancy and were treated with either Ruconest, Firazyr, Berinert (plasma-derived, pasteurized, nanofiltered C1-inhibitor, pnfC1-INH) or Cinryze (plasma-derived, nanofiltered C1-INH, nfC1-INH).
For the six pregnancies in all, 79 HAE attacks — 23 in the first trimester, 36 in the second trimester, and 30 in the third trimester — were reported. Most were abdominal (67.1%), followed by peripheral (26.6%), facial (12.7%), and laryngeal (12.7%) edemas. In 16.5% of cases, attacks were combined and affected more than one region at a time.
More than half (63.3%) of the attacks were treated with Ruconest, followed by Berinert in 21.5%, Firazyr in 16.5%, and Cinryze in 1.3%. In five attacks (6.3%) experienced by one of the patients with HAE type 2, the treatment had to be repeated.
“After the initial treatment, the patient reported a temporary improvement in symptoms; however, the attack symptoms recurred. In all cases, the second treatment was effective,” researchers wrote.
All patients were able to carry their babies to full term, and all six deliveries — one Cesarean section and five spontaneous vaginal deliveries — occurred with no complications. Newborns had a healthy birth weight ranging from 2,850 (about 6.3 pounds) to 3,690 grams (8.1 pounds) and did not have any congenital abnormalities.
“According to the U.S. Food and Drug Administration, rhC1-INH’s pregnancy category is B [while] icatibant is in pregnancy category C, [meaning that] animal reproduction studies have not demonstrated a risk to the foetus [in the former], but have shown an adverse effect on the foetus [in the latter],” the researchers wrote.
“[Nevertheless,] our results show good rhC1-INH or icatibant treatment efficacy for HAE attacks during pregnancy [with no associated side effects]. However, long-term data on larger populations are required to confirm the safety of rhC1-INH and icatibant,” they added.