Understanding hereditary angioedema and its treatment
Hereditary angioedema (HAE) is a rare genetic disorder characterized by recurring episodes of severe swelling. These attacks, caused by excess bradykinin, can affect various parts of the body, including the face, extremities, gastrointestinal tract, and, most dangerously, the upper airway. Managing HAE involves two main strategies: long-term prophylaxis (preventing attacks) and on-demand treatment (addressing acute attacks as they occur). Historically, many effective treatments required injections or infusions, but pharmaceutical advancements have introduced oral options that have revolutionized patient convenience and control.
The oral pill for preventative HAE treatment: Orladeyo (berotralstat)
One of the most significant developments in oral HAE management is the availability of Orladeyo, the brand name for the drug berotralstat. It is a plasma kallikrein inhibitor used for long-term prophylaxis against HAE attacks.
How Orladeyo works
In people with HAE, low levels of C1 esterase inhibitor (C1-INH) lead to excessive activity of plasma kallikrein, an enzyme that triggers the overproduction of bradykinin. Berotralstat works by blocking the activity of this enzyme. By inhibiting plasma kallikrein, Orladeyo helps prevent the cascade that leads to swelling and pain, effectively reducing the frequency of attacks.
Usage and considerations for Orladeyo
- Administration: Orladeyo is typically taken as a single capsule once daily with food. Taking it with food can help reduce stomach-related side effects.
- Age and patient population: It is approved for use in adults and pediatric patients 12 years of age and older.
- Safety: It's crucial not to exceed the prescribed daily amount, as higher quantities can increase the risk of heart rhythm problems, such as QT prolongation. Patients should also inform their doctor if they have liver problems, as adjustments may be necessary.
- Not a rescue medication: Orladeyo is not used to treat acute HAE attacks once they have already started. Patients on preventative therapy should still carry a separate rescue medication for breakthrough attacks.
The oral pill for acute HAE attacks: Ekterly (sebetralstat)
Ekterly, known by its generic name sebetralstat, is another breakthrough oral medication for HAE. It is the first and only FDA-approved oral treatment for acute HAE attacks. This on-demand therapy offers a convenient, non-injectable alternative for patients to use at the first sign of an attack.
How Ekterly works
Similar to Orladeyo, Ekterly is also a plasma kallikrein inhibitor. When taken at the onset of an attack, it blocks the activity of the enzyme responsible for creating the excess bradykinin that causes swelling. This inhibition helps stop the progression of the attack and provides rapid symptom relief.
Usage and considerations for Ekterly
- Administration: Ekterly is typically taken orally at the first sign of an acute attack. A second quantity may be taken some hours later if symptoms persist.
- Age and patient population: Ekterly is approved for patients 12 years and older.
- Side effects: The most common side effect reported in clinical trials was headache.
- Convenience: As an oral capsule, Ekterly is easier to carry and administer than injected or infused on-demand treatments, allowing for quicker intervention and potentially better outcomes.
Comparison of oral HAE treatments: Orladeyo vs. Ekterly
| Feature | Orladeyo (Berotralstat) | Ekterly (Sebetralstat) |
|---|---|---|
| Purpose | Long-term prophylaxis (prevention) | On-demand treatment (acute attacks) |
| Administration | Once-daily oral capsule | Oral tablets (two per dose) |
| Mechanism | Plasma kallikrein inhibitor | Plasma kallikrein inhibitor |
| Usage timing | Taken daily, regardless of symptoms | Taken at the onset of an attack |
| Common side effects | Abdominal pain, vomiting, diarrhea | Headache |
| Serious risk | Heart rhythm problems (with misuse) | None commonly reported (on-demand use) |
| Age approval | 12 years and older | 12 years and older |
The broader landscape of HAE treatment
While oral medications are a significant step forward, other non-oral therapies continue to play a vital role, especially for those who require infusions or have difficulty with oral administration. Non-oral options include:
- Injectable Preventatives: Lanadelumab (Takhzyro) is an injectable plasma kallikrein inhibitor for prophylaxis. Subcutaneous C1 esterase inhibitors (Haegarda) and intravenous C1 esterase inhibitors (Cinryze) are also used for prevention.
- Injectable On-Demand: Injectable C1 esterase inhibitors (Berinert), bradykinin B2 receptor antagonists (icatibant/Firazyr), and plasma kallikrein inhibitors (ecallantide/Kalbitor) are used to treat acute attacks.
Conclusion: The power of choice in HAE management
The availability of oral medications like Orladeyo and Ekterly represents a major milestone in the management of hereditary angioedema. For years, patients relied solely on injections and infusions, which, while effective, can be burdensome and challenging to administer, especially in emergency situations. These oral options offer increased flexibility and independence, empowering patients to manage their condition more effectively and conveniently. For those with HAE, having a choice between an easy-to-take daily pill for prevention and a rapid-acting oral capsule for acute attacks provides a level of control that can dramatically improve quality of life. As always, patients should consult with a healthcare professional to determine the most appropriate treatment plan for their specific needs. For more information and resources, patients can visit the Hereditary Angioedema Association at https://www.haea.org/pages/p/treatments.
Disclaimer
This information is for general knowledge and should not be taken as medical advice. Consult with a healthcare professional before starting any new supplement regimen.
