HAE treatment-switching process varies among patients: Study
Switching to Orladeyo or Takhzyro may mean fewer swelling episodes
Transitioning from other prophylactic, or preventive, treatments, to Orladeyo (berotralstat) or Takhzyro (lanadelumab) can take some time and adjustment, but helps to safely prevent swelling episodes in hereditary angioedema (HAE) patients.
That’s according to a study reporting the process of such a treatment transition for four family members with HAE.
“The transition journey,” the researchers wrote, “may not be straightforward and is specific to each patient.” This can be true even when patients share the same genotype, or genetic makeup, behind the disease, as was in this case. The case series may help to inform future transition guidelines, the researchers said.
The study, “Androgen transition and management of hereditary angioedema long-term prophylaxis in real life: a single-center case series,” was published in the Orphanet Journal of Rare Diseases with support from Biocryst Pharmaceuticals, which markets Orladeyo.
HAE causes recurrent swelling episodes in various parts of the body, but long-term prophylaxis can “reduce the frequency and duration of episodes and therefore prevent life-threatening complications,” the researchers wrote.
Many patients still on older treatments
Targeted prophylactic medications like Orladeyo, taken orally once daily, or Takhzyro, given via under-the-skin injections once every two or four weeks for adults, are recommended as first line treatment for HAE.
However, many patients remain on older, non-targeted prophylactic treatments, such as attenuated androgens or tranexamic acid, “in light of ease of access, price and patient habituation,” the researchers wrote. Notably, attenuated androgens “have several limitations related to efficacy, adverse effects (AEs) and contraindications,” they added.
There is limited evidence on the transition between long-term prophylactic treatments, especially from older medications to Orladeyo, the researchers noted.
To fill this knowledge gap, the team of researchers in France described how four family members transitioned to long-term targeted prophylaxis. All had HAE type 1, and were diagnosed between the ages of 5 and 12.
“Despite having the same genotype there was variability in patient management, both in relation to the type of treatment given and the transition to new therapy,” the researchers wrote. “As such they each received an individualized treatment plan.”
The first patient described in the study was a 52-year-old man who had been on danazol, an attenuated androgen, for more than two decades. He decided to change treatment due to the risks of long-term androgen use.
He started on Orladeyo, and was instructed to take a low danazol dose. However, he deviated from the plan and was taking his initial danazol dose, as he experienced three swelling episodes after starting treatment change. He eventually stopped Orladeyo treatment, and continued on his danazol initial dose due to anxiety related to the transition process and two additional swelling attacks.
An adjusted transition plan was designed to gradually reduce the dose of danazol while reintroducing Orladeyo. After eight months, the man’s swelling episodes were under control with Orladeyo and a low danazol dose, and after 11 months, danazol was discontinued. He remained free of swelling episodes for at least six months on Orladeyo alone.
Family members switch HAE treatments, with varying experiences
Another patient, the man’s 21-year-old daughter, was first treated with tranexamic acid and then with chlormadinone, a type of hormonal treatment, due to frequent swelling episodes requiring on-demand treatment.
However, she did not tolerate chlormadinone well, and was switched to Takhzyro. She experienced headaches and vomiting in the first month, but the treatment stopped swelling attacks. After several months, she transitioned to Orladeyo “as the injections negatively affected her quality of life and mood,” the team wrote.
“Other than a mild attack seven months later, that did not require on-demand treatment, she has remained attack-free since the transition,” they added.
A 50-year-old woman, a sister of the man, took danazol intermittently for over 20 years. She decided to transition to Orladeyo when it became available based on an assessment of danazol’s risk-benefit balance.
Despite a transition plan to gradually reduce, and subsequently discontinue, danazol over six weeks while starting on Orladeyo, the plan took nearly 1.5 years to complete due to the occurrence of HAE attacks.
While she was satisfied with Orladeyo after that period, reporting no side effects, she restarted low-dose danazol, and has been instructed to again further reduce the dose.
The woman’s 19-year-old daughter was prescribed tranexamic acid for long-term prophylaxis and Firazyr (icatibant) for on-demand treatment as a child. However, by age 13 she reported that she was not using Firazyr because of fear of self-injection.
Two years later, she was started on Takhzyro, administered by a nurse. After two years and some adjustments on treatment frequency, she had learned to self-inject and her disease was well managed.
Adverse events during transition were mild and resolved after patients were well established on the new therapy. Three patients experienced swelling episodes during the transition process, but only one required on-demand treatment with Firazyr.
“Patients should be followed closely during the transition process,” the researchers wrote. “Following patients closely during the transition period helps identify any issues, including difficulties with treatment adherence, and may allow the transition plan to be adapted when necessary.”
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