Kalbitor Has Potential as Treatment for Angioedema Attacks in Lupus Teens Who Have Normal C1-IHN Levels, Case Reports Contend

Kalbitor (ecallantide) is a potential treatment for angioedema attacks that do not respond to medication, in adolescents who also have systemic lupus erythematosus (SLE), even if they have normal levels of C1 inhibitor protein, two case reports suggest.

The study combining the reports, “Ecallantide: An alternative treatment of refractory angioedema in adolescents with systemic lupus erythematosus,” was published in The Journal of Allergy and Clinical Immunology: In Practice.

Some cases of idiopathic angioedema seem to be associated with autoimmune disorders such as SLE. People with autoimmune diseases can produce autoantibodies — antibodies that mistakenly attack healthy proteins — against C1 inhibitor protein, reducing the levels of that protein and making the patients prone to angioedema attacks.

Shire‘s Kalbitor is a treatment for hereditary angioedema (HAE) that inhibits kallikrein, a protein that causes swelling when the levels of C1 inhibitor protein are low. The therapy is approved for people 12 or older.

Researchers reported the cases of two adolescents who developed angioedema after being diagnosed with SLE and responded well to treatment with Kalbitor.

The first patient was a 13-year-old Caucasian girl, who had been diagnosed two years earlier with SLE and Grave’s disease, an autoimmune disorder that reduces hormone production in the thyroid gland.

The girl had an acute angioedema attack after receiving an acyclovir injection to treat herpes infection. The researchers said that acyclovir probably triggered the attack.

The patient had swelling in her eyelids, lips, and tongue. She received treatment with epinephrine (adrenaline), methylprednisolone (a corticosteroid), and an antihistamine, but swelling persisted and progressed to her airways. The doctors gave her two doses of Kalbitor, which reduced the swelling.

Lab tests performed during the angioedema attack showed low levels of the complement proteins — members of the immune systems that get depleted in people with autoimmune diseases — and autoantibodies against different molecules, including C1 inhibitor protein. In spite of autoantibody presence, the girl had normal levels of C1 inhibitor protein.

The doctors discharged the patient after adjusting her SLE medication. She did not present any angioedema attacks in the following year.

The second patient was a 17-year-old Caucasian boy who had been diagnosed recently with SLE and lupus nephritis, a complication of SLE that affects kidney function.

The boy developed an angioedema attack causing lip, tongue, and airway swelling after receiving a blood transfusion.

The patient was intubated and treated with epinephrine and methylprednisolone with no improvement. His swelling got better some hours after receiving two doses of Kalbitor. The boy was extubated and discharged two days after the treatment.

Lab exams during the angioedema attack showed low complement levels and autoantibodies against C1 inhibitor protein, but normal levels and activity of the protein.

“Although both patients developed angioedema during active SLE, the normal level of C1-INH [C1 inhibitor protein] and activity levels imply that consumption of C1-INH by autoantibodies is not the primary cause of angioedema in these patients,” the investigators said.

The boy still needs treatment for SLE, but did not have any angioedema attacks in the following two years.

“Ecallantide may be a potential treatment option for acute, refractory angioedema in SLE patients,” the investigators wrote. “We also suspect that another kallikrein inhibitor, lanadelumab [approved as Takhzyro], might be a possibility as [preventive treatment] for SLE patients with frequent severe angioedema attacks.”