Hereditary Angioedema Treatment: Medication, Lifestyle Changes, and More
Hereditary angioedema (HAE) is a genetically inherited disorder that causes episodes of severe swelling of the limbs, face, digestive system, and airways. Not every attack has a known trigger, but stress or injury can lead to episodes.
The type of HAE a person has depends on their blood levels of a protein called C1 esterase inhibitor (C1-INH). People with type 1 HAE have low levels of C1-INH, while those with type 2 HAE have normal C1-INH levels but with a protein that doesn’t work correctly.
In the past, doctors commonly prescribed attenuated androgens (synthetic versions of male hormones) to prevent hereditary angioedema attacks. While these medicines are sometimes useful, they can cause serious side effects, such as liver problems, high cholesterol or blood pressure, mood swings, and damage to reproductive organs.
Today, many healthcare providers opt for alternative treatments to attenuated androgens. There are two kinds of hereditary angioedema treatments: preventive and on-demand.
Preventive or Prophylactic Therapies People with HAE take this type of medication regularly to help ward off an HAE attack. These medications can also help reduce the frequency and severity of your symptoms. A doctor may recommend long-term prophylactic medications to reduce the overall burden of attacks, but might prescribe short-term preventive medicines ahead of a surgical or dental procedure that puts stress on the body.
On-Demand or Acute Treatments This type of therapy helps to stop an attack that’s already in progress. Everyone with HAE should have access to an on-demand therapy, as prophylactic medications may not be 100 percent effective.
Currently, the U.S. Food and Drug Administration (FDA) has approved nine medicines to prevent or treat HAE attacks, including these classes of medications. All except one have approval for people to administer the medications without the help of a medical professional.
C1 Esterase Inhibitors (C1-INH)
These work by replacing C1-INH in the blood. C1-INH is a protein that helps regulate swelling and inflammation. By returning levels of C1-INH to normal, these injected medications can either prevent attacks from happening or treat HAE episodes as they occur.
The FDA has approved several C1-INH treatments for HAE, and two types are available. Plasma-derived C1-INH comes directly from part of human blood, while technicians create recombinant C1-INH using genetic engineering in host cells.
Plasma-derived C1-INH inhibitors are suitable for adults and children and include the brands:
Cinryze
Haegarda
Berinert
Only one recombinant C1-INH medication for HAE, Ruconest, is available for adults and adolescents with HAE, though it is contraindicated in people with an allergy to rabbit. People take Cinryze or Haegarda to prevent HAE attacks and Berinert or Ruconest to treat active HAE episodes.
Preventive C1-INH medications come as a powder that needs mixing with liquid and injecting under the skin (subcutaneous injection). Berinert and Ruconest require injecting into a vein (intravenous) rather than under the skin due to the need for rapid action during an episode.
If you feel comfortable self-injecting, you or a carer can do this at home, or you can have a healthcare professional administer the injection. Injections last 5 to 10 minutes and you’ll need one every three to four days for preventive medications.
Depending on the medication, side effects might include headache, nausea, vomiting, a bad taste in the mouth, fever or chills, injection site redness or pain, runny nose, sneezing, watery eyes, a sore throat, or dizziness. See a doctor about symptoms suggesting an allergic reaction, such as hives, rash, itching, breathing or swallowing difficulties, blue-tinted lips and skin, swelling of your face, tongue, or throat, sweating, hoarseness, lightheadedness, or fainting.
“Plasma-derived C1-esterase inhibitor is approved for long-term prophylaxis (Cinryze) and treatment of acute attacks (Cinryze and Berinert),” confirms Meng Chen, MD, clinical assistant professor in pulmonary, allergy, and critical care medicine at Stanford Medicine in California. “Recombinant C1-esterase inhibitor has approval for the treatment of acute attacks (Ruconest).”
Dr. Chen advises that both types of C1-esterase inhibitors are considered effective, and testing has not occurred to check whether one type carries more risks than the other. “Both are generally well tolerated with rare adverse events. However, people who are allergic to rabbits should not receive Ruconest, given that rabbits play a role in its production,” Chen advises.
Kallikrein Inhibitors
This class of medications is a monoclonal antibody, meaning they target and block the activity of a specific enzyme. Kallikrein inhibitors disrupt kallikrein, an enzyme with which C1-INH interacts to prevent swelling in healthy individuals.
Kallikrein inhibitors include:
lanadelumab (Takhzyro)
berotralstat (Ordaleyo)
sebetralstat (Ekterly)
Lanadelumab is a subcutaneous injection, while people can take berotralstat or sebetralstat as a daily pill. Lanadelumab and berotralstat are preventive medications, while sebetralstat is the first oral pill that’s available to treat acute attacks.
Common side effects differ between kallikrein inhibitors but may include abdominal pain, vomiting, diarrhea, back pain, gastroesophageal reflux disease (GERD), injection site reactions, upper respiratory infections, headache, rash, and dizziness.
Bradykinin B2 Receptor Antagonists
These medications target bradykinin, a molecule involved in causing HAE episodes. This enzyme affects the widening of blood vessels, and excess kallikrein during HAE can break down too many other blood components into bradykinin. This increases blood vessel dilation in the airways and gut, contributing to HAE swelling.
However, people with HAE can use bradykinin B2 receptor antagonists during an attack to treat symptoms. The bradykinin B2 receptor antagonists with FDA approval to treat HAE include:
icatibant (Firazyr)
ecallantide (Kalbitor)
Icatibant is only suitable for adults, while adolescents and adults can use ecallantide. Side effects can involve burning, numbness, swelling, pain, a feeling of pressure, and warmth. Headaches, nausea, fever, rash, and dizziness are also common side effects. As both medications are subcutaneous injections, itching, redness, pain, irritation, hives, and bruising might also occur.
Activated Factor 12a (F12a) Inhibitors
The most recently approved HAE medication is garadacimab (Andembry), a preventive monoclonal antibody that targets the protein factor 12a (F12a) in the blood.
This protein in plasma kicks off a chain reaction known as the kallikrein-kinin cascade, which triggers HAE attacks. By targeting factor 12a, garadacimab blocks the cascade at the top, unlike other HAE therapies that target kallikrein or bradykinin, which occur further down the chain. “The advantage of activated factor 12a inhibitors blocking the HAE response close to the top of the kallikrein-kinin cascade is in blocking the downstream inflammatory cascade that leads to swelling during HAE attacks,” Chen suggests.
People with HAE take garadacimab as a monthly subcutaneous injection. It is available for use as a prefilled pen for self-injection, known as an auto-injector, which delivers the medication in 15 seconds or less.
Psychological stress is among the most common triggers for HAE attacks. Plus, HAE has shown a range of psychological effects in narrative studies, including depression, anxiety, isolation, and feeling paranoid about the risk of attacks. “Mental health support is important for protecting mental health with HAE,” confirms Chen. “Patients can benefit from mental health services to manage the psychological impact of a chronic medical condition.”
This can lead to a cycle in which depression, anxiety, and post-traumatic stress disorders (PTSD) develop due to attacks but also trigger further attacks. Depending on the individual, these may include:
Getting enough rest
Exercising daily
Practicing meditation, deep breathing techniques, or yoga
Getting a massage
“Addressing the psychological impact of HAE is important for the treatment plan,” suggests Chen. “This can help improve the overall quality of life for the patient and mitigate stress, which may trigger HAE attacks.”
However, while stress and trauma occasionally trigger HAE attacks, most occur without any known trigger or cause.
Talk to your doctor about which medicines are most appropriate for treating your HAE attacks.
Guidelines suggest that everyone with HAE should have an on-demand treatment plan.
If you have frequent episodes, your physician might suggest both a preventive and an on-demand therapy. The severity of your attacks and your general health will also factor into your doctor’s recommendations.
The FDA-approved therapies are typically used to treat the most common kinds of HAE: type 1 and type 2. Clinical trials are underway to uncover new medicines that could help HAE in the future.
