A patient with hereditary angioedema with normal C1 inhibitor (HAE-nC1) and negative genetic testing experienced reduced attack severity and approximately 80% lower attack frequency as a result of treatment with anti-kallikrein biologic medication lanadelumab, according to a case report published in the Journal of Allergy and Clinical Immunology: Global.
The study authors reported on a 62-year-old female patient with long-term recurrent angioedema of her tongue, larynx, extremities, and abdomen. Treatment with high-dose antihistamines (cetirizine 40 mg per day for 12 weeks) and oral glucocorticosteroids (prednisone 60 mg daily for 24 weeks) did not provide symptom relief. The patient was never trialed on omalizumab.
Repeated testing of her serum C4 concentration and C1 inhibitor concentration and function showed no abnormalities. Moreover, gene sequencing of FXII, PLG, ANGPT1, and SERPING1 did not identify any pathogenic variants.
The patient previously experienced approximately 3 angioedema attacks per week. Acute treatment with subcutaneous icatibant led to noticeable symptom relief within 30 minutes and prevented the need for emergency department care, but she still experienced frequent swelling. Due to the incidence and unpredictability of the swelling episodes, the patient’s quality of life as well as her occupational and social activities were significantly impaired.
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The patient was offered an intravenous plasma-derived C1 inhibitor for the treatment of acute attacks and long-term prophylaxis, but she could not administer it on her own due to vision impairment.
After being started on 300 mg of subcutaneous lanadelumab every 2 weeks, her average attack frequency decreased from approximately 12 to 2 per month and the attacks became mild enough that she could refrain from using icatibant.
At the last visit, the patient’s angioedema control test score was 14 (out of a possible 16 points with scores higher than 10 indicating well-controlled disease).
“The successful use of lanadelumab in this case, suggests that kallikrein plays a central role in the pathophysiology in at least a subset of patients with HAE-nC1, which is likely a genetically and physiologically heterogenous condition,” Adatia and Ritchie wrote.
“This finding supports further investigation of the contact pathway in the search for additional monogenic causes of the HAEnC1 phenotype. HAE-nC1 patients who do not respond to lanadelumab may conversely have novel disease mechanisms that do not involve the contact pathway.”
In the absence of randomized controlled trials with patients with HAE-nC1, there are no approved therapies for this condition and patients are treated similarly to those with HAE caused by C1-inhibitor deficiency.
Adatia A, Ritchie B. Successful use of lanadelumab in a patient with hereditary angioedema with normal C1 inhibitor and negative genetic testing. J Allergy Clin Immunol. Published online February 21, 2023. doi:10.1016/j.jacig.2023.100087.