Understanding hereditary angioedema (HAE)

Managing hereditary angioedema (HAE), a disruptive and sometimes deadly disease, can be difficult and costly for patients and plan sponsors alike, with much variability among people who have this condition. Here are some of the most important things to know about HAE. 

What is HAE? 

HAE is an extremely rare genetic condition that involves periodic attacks of severe, potentially life-threatening swelling of the subcutaneous tissue. The condition is most often associated with damaged or deficient C1 esterase inhibitor (C1-INH), a protein that regulates swelling. In the absence of functional C1-INH, overexpression of a peptide called bradykinin can occur. Bradykinin triggers movement of fluid from blood vessels into tissues, resulting in swelling.

There are three types of HAE:

• HAE type I comprises approximately 80 to 85% of cases and is caused by a deficiency of C1-INH.
• HAE type II comprises approximately 15% of cases and is caused by dysfunction of C1-INH.
• HAE with normal C1 esterase inhibitor, whose prevalence is unknown, is caused by distinct genetic mutations that drive increased bradykinin expression but are unrelated to C1-INH presence or function.

Swelling episodes can be triggered by: 

• repetitive physical activity, 
• anxiety, 
• menstruation,
• fatigue,
• stress, 
• trauma, 
• surgery, 
• dental procedures,
• weather changes,
• infections, 
• diet, 
• medication 

or occur in the absence of a known trigger. Episodes may be life-threatening if they occur around the patient’s airway or abdomen. Disease severity is variable; patients may experience one swell per year up to two or three swells per week. The condition affects approximately 6,000 patients in the U.S., and is typically diagnosed in childhood. 

How does HAE treatment work?

Traditional anti-swelling therapies—like antihistamines, corticosteroids and epinephrine—are ineffective for treating HAE. Every patient has a unique drug regimen and dosage requirement, with multiple perspectives between prescribers and pharmacists. Depending on the patient’s age and family history, varying levels of support may be needed, with more care required for infused versus oral treatments.

Acute swelling attacks are treated with on-demand C1-INH replacements such as Berinert® or Ruconest®, which are administered intravenously. Alternatively, patients may receive the kallikrein inhibitor Kalbitor® or the selective bradykinin b2 receptor antagonist Firazyr®, both injected subcutaneously. 

Patients who have life-threatening attacks are often treated with long-term prophylaxis. These drugs include an oral medication (Orladeyo^®), a subcutaneous injection (Takhzyro^®) or infused C1-INH concentrates (Cinryze^®, Haegarda^®).

Multiple potentially curative therapies using CRISPR gene editing technology are in clinical trials, with the possibility of approval this decade. While the arrival of these treatments could be transformative for patients, it’s reasonable to assume they will be cost-prohibitive like many other gene therapies in the pipeline. 

What should plan sponsors know about HAE?

There are many variables that can make HAE unpredictable for plan sponsors. Because every patient presents differently and the number of swells varies greatly by patient, it can be difficult to budget costs. Some patients may be on prophylactic treatments, some may only need on-demand treatment, while the most expensive patients are usually on a combination of both. 

Because up to one-third of patients will experience a life-threatening attack¹, every single swell should be considered for treatment regardless of location. A single attack can cost as much as $30,000, which may come as an unwelcome surprise for smaller plan sponsors.

In many ways, much of what’s true about hemophilia can also be considered true about HAE—simply replace the word “bleed” with “swell.” However, because the prevalence is significantly lower than hemophilia, which has as many as 40,000 patients in the U.S.,² some plan sponsors may have no patients with HAE, while others might have an entire family with the disease. Awareness and education are the best ways to avoid fire drills when it comes to this condition.

Accredo’s approach to HAE care

Accredo’s Therapeutic Resource Center for HAE helps to transform care for this troubling, expensive disease state with an unmatched team of pharmacists, nurses and customer service representatives.

Pharmacists conduct clinical assessments and counsel each HAE patient individually when they join Accredo and throughout their care journey—teaching them about their medications, answering any clinical questions they have and offering gap-in-care rescue calls as needed to improve adherence. 

Telephonic and at-home nursing support is available 24/7, and proactive social work support is offered to severe and life-threatened HAE patients for a whole-person health experience. Accredo is also committed to reducing waste through our vial and regimen optimization programs in HAE—programs that directly result in payer savings.³

Ultimately, patients reap the benefits of our advanced TRC care model, with a team of experts to collaborate and consult on their drug regimen, while one-of-a-kind reporting allows plan sponsors to track a patient’s journey against cost, and see what causes spend to progress.