Switch to Takhzyro found to reduce cardiovascular risk for HAE patient
Use of approved therapy also prevented swelling attacks for man, 56: Report
Switching from long-term androgen treatment to Takhzyro (lanadelumab) successfully prevented swelling attacks and reduced cardiovascular risk in a man with hereditary angioedema (HAE) type 1, according to a report from Italy.
The man had undergone two kidney transplants and was on immunosuppressant medications for several years.
According to the researchers, cardiovascular conditions “represent the first cause of death in … patients [with kidney issues] and are among the leading causes of mortality in patients with hereditary angioedema” like that found in this man.
“The successful outcomes of this case highlight the potential of [Takhzyro] as a promising prophylactic [preventive] therapy,” the researchers wrote.
Further, “during the 13-month follow-up period, our patient showed no evidence of infections or adverse side effects” with Takhzyro use, the team added.
The study, “Lanadelumab in a kidney transplant patient with hereditary angioedema due to C1-inhibitor deficiency and high cardiovascular risk – a case report,” was published in the journal Frontiers in Immunology.
Researchers detail case of HAE patient with high cardiovascular risk
Hereditary angioedema, known as HAE, is characterized by the excessive production of bradykinin — a molecule that regulates blood pressure by promoting the widening of blood vessels — which causes fluid to leak out from blood vessels and accumulate in nearby tissues, causing swelling.
The condition is commonly caused by mutations in the SERPING1 gene that impair the production or function of a protein called C1-inhibitor, or C1-INH. The C1-INH protein regulates bradykinin levels by blocking kallikrein and coagulation factor 12, proteins that promote the production of bradykinin.
Until the approval of Takhzyro, antibody-based therapies designed to block kallikrein — specifically, treatments such as danazol and stanazolol — were most commonly used to prevent swelling attacks. However, these medications, which have a similar structure to the male sex hormone (androgen) testosterone, may increase the risk for cardiovascular conditions. That is not a common side effect of Takhzyro.
Here, the team of researchers described the case of a 56-year-old man who had his first angioedema episode, affecting one arm, in 1984, at the age of 17. He was started on immunosuppressive therapy including corticosteroids and cyclosporine, after blood work revealed evidence of acute renal failure.
Disease progression made him need hemodialysis — a treatment that filters wastes, salts, and fluid from the blood in the way kidneys do when they are healthy.
In the following five years, he experienced an average of two swelling attacks per month, mainly affecting the face or limbs. Treatment with standard therapy was not successful. He was diagnosed with HAE C1-INH type 1, with low C1-INH levels and activity. His children also developed angioedema later, confirming the diagnosis of HAE-C1INH type 1.
The man was treated with plasma-derived C1-INH, given intravenously, or into the vein, to treat swelling attacks. However, given the frequency of the attacks, the patient was prescribed long-term preventive treatment with stanozolol, an attenuated version of androgen, which reduced attack frequency to about one per year.
Patient had second kidney transplant in 2023, then started Takhzyro
About seven years after first seeking treatment, the man underwent a kidney transplant, restarting his use of steroids and cyclosporine. In 1994, his preventive treatment was changed to danazol (100 mg), which was equally effective as stanazolol. But because the man also developed myocardial hypertrophy — thickening of the heart muscle, making it harder for the heart to pump blood — his immunosuppressive treatment was changed to mycophenolate in 2002, when he was 35.
After 10 years of stable clinical status, the patient developed cyclosporine-induced kidney damage, which led to transplant rejection and the need to restart dialysis.
“This procedure, probably together with psychological stress, resulted in a [recurrence] of HAE attacks, and the dose of Danazol was increased to 100 mg [twice daily],” the researchers wrote.
The man underwent a second kidney transplant in 2018. Since then, his immunosuppressive treatment included mycophenolate, tacrolimus, and prednisone.
When the man was 56, in 2023, his cardiovascular risk, as assessed with kidney disease measures, was 13.2% at 10 years. Given his report of weight gain as a side effect of danazol, that dose was reduced and he eventually stopped that treatment eight weeks later.
Treatment with Takhzyro, given at a 300 mg dose by subcutaneous, or under-the-skin, injection every two weeks, was started. This change in treatment regimen had been discussed with the patient.
[Takhzyro] is effective and safe in preventing hereditary angioedema attacks, as well as in reducing cardiovascular risk in an immunosuppressed patient with significant comorbidities [coexisting conditions].
After six months free from swelling attacks, the dosage was reduced to once every four weeks. At the last follow-up, the man remained asymptomatic and his cardiovascular risk decreased to 9.3% at 10 years.
Overall “[Takhzyro] is effective and safe in preventing hereditary angioedema attacks, as well as in reducing cardiovascular risk in an immunosuppressed patient with significant comorbidities [coexisting conditions],” the investigators wrote.
About the Author
