Successful Use of Lanadelumab in an Older Patient With Type II Hereditary Angioedema

Discussion

According to the international WAO/EAACI 2021 guidelines, HAE treatment goals are “to achieve complete control of the disease and to normalize patients’ lives.”⁸ On-demand treatment options include C1 esterase inhibitor, icatibant, or ecallantide (a kallikrein inhibitor).⁸ Long-term prophylaxis in HAE should be considered, accounting for disease activity, burden, control, and patient preference. Five medications have been used for long-term prophylaxis: antifibrinolytic agents (not recommended), attenuated androgens (considered second-line), C1 esterase inhibitor, berotralstat, and lanadelumab.⁸

Antifibrinolytics are no longer recommended for long-term prophylactic treatment as their efficacy is poor and was not considered for our patient. Attenuated androgens, such as danazol, have a history of prophylactic use in patients with HAE due to their good efficacy but are suboptimal due to their significant AE profile and many drug-drug interactions.⁸ In addition, androgens have many contraindications, including hypertension and hypertriglyceridemia, which were both present in our patient. Consequently, danazol was not an advised treatment for our patient. C1 esterase inhibitor is often used to prevent HAE attacks and can be given intravenously or subcutaneously, typically administered biweekly. A potential AE of C1 esterase inhibitor is thrombosis.Therefore, C1 esterase inhibitor was not a preferred choice in our older patient with a history of hypercoagulability. Berotralstat, a plasma kallikrein inhibitor, is an oral treatment option that also has shown efficacy in long-term prophylaxis. The most common AEs of berotralstat tend to be gastrointestinal symptoms, and the medication requires dose adjustment for patients with hepatic impairment.⁸ Berotralstat was not considered because it was not an approved treatment option at the time of this patient’s treatment. Lanadelumab is a human monoclonal antibody against plasma kallikrein, which decreases bradykinin production in patients with HAE, thus preventing angioedema attacks.⁵ Data regarding the use of lanadelumab in patients with type II HAE are limited, but because HAE with normal C1 esterase inhibitor levels involves the production of bradykinin via kallikrein, lanadelumab should still be effective.¹ Lanadelumab was chosen for our patient because of its minimal AEs and is not known to increase the risk of thrombosis.

Lanadelumab is a novel medication, recently approved in 2018 by the US Food and Drug Administration for the treatment of type I and type 2 HAE in patients aged ≥ 12 years.⁷ The phase 3 Hereditary Angioedema Long-term Prophylaxis (HELP) study concluded that treatment with subcutaneous lanadelumab for 26 weeks significantly decreased the frequency of angioedema attacks compared with placebo.⁵ However, 113 (90.4%) of patients in the phase III HELP study had type I HAE.⁵ Of the 125 patients that completed this randomized, double-blind study, only 12 had type II HAE.⁵ In addition, this study only included 5 patients aged ≥ 65 years.⁵ Also, no patients aged ≥ 65 years were part of the treatment arms that included a lanadelumab dose of 300 mg.⁵ In a case series of 12 patients in Canada, treatment with lanadelumab decreased angioedema attacks by 72%.⁹ However, the series only included 1 patient with type II HAE who was aged 36 years.⁹ Therefore, our case demonstrates the efficacy of lanadelumab in a patient aged ≥ 65 years with type II HAE.

Conclusions

HAE is a rare and potentially fatal disease characterized by recurrent, unpredictable attacks of edema throughout the body. The disease burden adversely affects a patient’s quality of life. Therefore, long-term prophylaxis is critical to managing patients with HAE. Lanadelumab has been proven as an effective long-term prophylactic treatment option for HAE attacks. This case supports the use of lanadelumab in patients with type II HAE and patients aged ≥ 65 years.

Acknowledgments

The patient was initially written up based on his delayed diagnosis as a case report.³ An earlier version of this article was presented by Samuel Weiss, MD, and Derek Smith, MD, as a poster at the American Academy of Allergy, Asthma, and Immunology virtual conference February 26 to March 1, 2021.