Therapeutic Progress for Patients With Hereditary Angioedema


Diagnostic delay tends to be a challenge for patients with hereditary angioedema, a rare but serious condition affecting 1 in 50,000 individuals.

Diagnostic delay is a tragedy for many patients, as it increases the burden of disease and extends time to symptomatic relief or an actual cure. Diagnostic delay tends to be a challenge for patients with hereditary angioedema (HAE), a rare but serious condition affecting 1 in 50,000 individuals.

During a continuing education session on Monday at the Asembia Specialty Pharmacy Summit 2019, Mark A. Malesker, PharmD, FCCP, FCCM, FASHP, BCPS, said patients who have HAE develop episodes of edema, often in their skin, gastrointestinal tracts, or upper respiratory tracts. Most patients do not experience itching, but some do. These episodes can last from 2 to 5 days and occur every few weeks.

“Each individual’s disease severity is different, and in the worst cases, laryngeal involvement can cause fatal asphyxiation,” Malesker said. “Swelling in other areas may cause obstruction of organs.” He added that the United States is home to 8000 of the 200,000 people who have HAE globally.

HAE is not simply a single condition but rather an autosomal dominant disease that manifests in different ways. Malesker indicated that this condition is most often a genetic aberration that causes decreased production of the enzyme C1-INH; however, some patients may have normal levels of C1-INH, in which case those individuals have dysfunctional enzymes. In a third group, genetic defects in factor XII have been reported.

“Most of these patients start to have attacks as children or adolescents but are not appropriately diagnosed for years,” Malesker said. “Some of these patients become nearly unrecognizable when swelling occurs in the face. Nearly half of patients will have a laryngeal attack sometime during the course of their disease."

Swelling from third spacing, fluid shifts from the intravascular compartment to a body compartment, frequently causes hypotension. The wide variability in disease expression and HAE’s unpredictable course are responsible for the delayed diagnosis. The disease is often confused with allergies or other medical conditions, but a key difference is that it does not respond to antihistamines, corticosteroids, or epinephrine.

Malesker noted that patients must have comprehensive treatment plans so they will have treatment options for acute attacks, short-term prophylaxis when they face a procedure or another stressor, and long-term prophylaxis if they experience frequent attacks. Clinicians must tailor treatment plans to the individual patient and specifically address emergency care, home supply of medications, and means of communication with hospitals when acute treatment is needed.

Fortunately, symptomatic management—an intervention that is needed within 8 hours of the start of symptoms—is available with antiemetics, opioid analgesics, and fluid support. Additionally, a number of pharmacologic interventions are also available for acute attacks, including C1 esterase inhibitor, C1 esterase inhibitor recombinant, icatibant, and ecallantide. Patients can self-administer most of these medications, which can reduce the number of attacks and sometimes nearly eliminate them.

Malesker also covered long-term prophylaxis and indicated that there are now 4 treatment options to help patients who are managed inadequately with stressor avoidance and on-demand treatment. These include attenuated androgens, anti brinolytics, C1 esterase inhibitors, and plasma kallikrein inhibitor lanadelumab-flyo. He noted that there are significant differences in the mode of administration, the costs, and the dosing frequency among these agents.

Cari W. Pao, PharmD, MBA, MSHCM, expanded on one of Malesker’s key points: that many treatments are costly. Pao stressed that the average annual cost of care for an individual with HAE is approximately $410,000, and she noted that drugs specifically developed for HAE accounted for 97% of total costs for the disease.

For many conditions, economic experts justify drug costs by noting that as costs increase, associated medical costs decrease. That is not the case with HAE, however, a condition in which drugs account for most of the medical spend. Pao indicated that any savings accrued must come from ensuring appropriate pharmacotherapy, presenting this fact as a strong case for pharmacist-directed case management.

Pao noted that case management involves working closely with individual patients to elucidate their specific triggers and symptoms. She advocated for pharmacist involvement on the clinical team with frequent communication with primary care providers, specialists, and nurse case managers.

“Patients appreciate pharmacists because they are touch points when they have medication questions [or] insurance issues or simply need a dose of compassion,” Pao said.

Pao also made note of the HAE Patient Declaration of Rights, which helps patients with HAE obtain the care they need. By reviewing this document, pharmacists will be able to ensure that patients have access to at least 2 standard doses of an FDA-approved therapy for on-demand treatment of acute attacks.

“Patients with HAE should never be required to take anabolic steroids and fail a trial before being prescribed an FDA-approved therapy,” Pao said. “FDA-approved therapies are necessities for these patients.”

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