Under-the-skin injections found to ease angioedema in pregnancy
Woman with type 3 HAE treated with subcutaneous C1-INH injections
A pregnant woman with type 3 hereditary angioedema (HAE) had potential swelling attacks effectively controlled during both pregnancy and breastfeeding with the use of subcutaneous or under-the-skin injections of a plasma-derived C1 esterase inhibitor (C1-INH), according to a case report from Spain.
Researchers say this may be the first time subcutaneous C1-INH injections were used to manage HAE in a type 3 patient during pregnancy and breastfeeding. More typically, intravenous or into-the-vein injections of C1-INH would be used, but such administration can lead to more complications.
“The current case report describes a successful experience of a patient with [type 3] HAE receiving off-label [subcutaneous plasma-derived C1-INH] during pregnancy (including pre-delivery), postpartum and breastfeeding, who experienced a reduction in both the number and severity of HAE attacks,” the team wrote, noting that the under-the-skin injections were “safe and effective in the patient.”
The case suggests that subcutaneous injections “could be a valuable option for the long–term prophylaxis [preventive treatment] of pregnant and breastfeeding patients,” according to the researchers.
The study, “Subcutaneous plasma derived C1 inhibitor for long-term prophylaxis during pregnancy and breastfeeding in a patient with Factor XII hereditary angioedema,” was published in The Journal of Allergy and Clinical Immunology: In Practice. The work was funded by CSL Behring, which markets the approved plasma-derived C1-INH concentrates Berinert and Haegarda.
Case may be the first of a pregnant woman treated with subcutaneous injections
HAE is caused by mutations that result in the overproduction of bradykinin, a signaling molecule that can trigger swelling attacks. HAE types 1 and 2 are caused by mutations that lower the levels or interfere with the activity of the C1-INH protein, which normally helps regulate bradykinin levels.
Type 3 HAE is a rarer form of the disease in which C1-INH levels and activity are normal. In up to 25% of cases, type 3 HAE is caused by mutations in the F12 gene, which provides instructions for making a blood clotting protein called coagulation factor 12 (FXII). These mutations increase the levels of activated FXII, which is involved in the production of bradykinin.
Plasma-derived C1-INH concentrates like Berinert and Haegarda are commonly used as long-term prophylactic treatments to prevent HAE swelling attacks.
While there have been quite a few reports describing the use of intravenous plasma-derived C1-INH concentrates in pregnant women, there are less reported data on the use of subcutaneous products during pregnancy.
“The evidence published with the subcutaneous (SC) preparation is scarcer in patients with HAE due to C1-INH deficiency, and non-existent in patients with [type 3] HAE,” the researchers wrote.
Now, the team described the case of a 35-year-old woman with type 3 HAE who used a subcutaneous plasma-derived C1-INH product off-label to manage swelling during pregnancy.
Since her late teens, the woman had been experiencing about two or three HAE swelling attacks per year, usually on her lips, face, and limbs. On several occasions, these attacks required emergency treatment.
She had previously given birth to four children, two boys and two girls, and had not experienced an increase in the number or severity of HAE attacks during pregnancy.
In early 2020, she became pregnant with twins. But a few weeks into the pregnancy she experienced a bout of swelling on her tongue that impaired her breathing and required her to be admitted to the intensive care unit.
She opted not to start long-term prophylactic therapy, and instead was sent home with instructions to resort to on-demand treatment with an intravenous plasma-derived C1-INH concentrate if needed. A few months later, however, her pregnancy ended, and she lost both twins.
Later that same year, the woman became pregnant again, and yet again experienced several bouts of tongue swelling that impaired her breathing. She was again given emergency care, and considering the frequency and severity of the episodes, was advised to start prophylactic treatment.
In the 29th week of her pregnancy, around the start of the third trimester, the woman started on an off-label prophylactic regimen of a plasma-derived C1-INH concentrate. The injections were given subcutaneously twice per week. Apart from a brief bout of lip swelling triggered by an injury, she did not experience any further swelling attacks during pregnancy.
At about 38 weeks into her pregnancy, the baby showed signs of distress in the womb, and was delivered via an emergency cesarean section, known as a C-section. A dose of intravenous C1-INH concentrate was administered 30 minutes before the C-section.
The baby, a boy, was healthy, and the patient continued prophylactic treatment with a subcutaneous C1-INH concentrate while breastfeeding, without any further swelling episodes or other complications to date.
To the best of our knowledge, this is the first report of the management of a patient with [type 3] HAE with [subcutaneous plasma-derived C1-INH] during pregnancy and breastfeeding.
This was especially notable, according to the researchers, given that both breastfeeding and surgeries like a C-section can act as triggers for HAE attacks.
“To the best of our knowledge, this is the first report of the management of a patient with [type 3] HAE with [subcutaneous plasma-derived C1-INH] during pregnancy and breastfeeding,” the researchers wrote.
Overall, the case “contributes to the generation of clinical evidence on the use of this … [long-term treatment option], not only in the difficult-to-study population of pregnant women, which are typically excluded from clinical trials, but also in women with normal levels of C1 esterase inhibitor and [F12] mutation,” the team wrote.
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