Lanadelumab may be an effective prophylactic treatment for hereditary angioedema

1. In this randomized controlled trial, prophylactic lanadelumab reduced attack frequency and severity in patients with hereditary angioedema compared to placebo.

2. The most common adverse reactions associated with lanadelumab treatment were injection site reactions and headache.

Evidence Rating Level: 1 (Excellent)   

Study Rundown: Hereditary angioedema is an autosomal dominant disorder caused by C1 inhibitory deficiency (type I) or dysfunction (type II). While current therapeutic options require frequent monitoring or intravenous access, subcutaneous injections of the human monoclonal antibody against kallikrein, lanadelumab, may be used prophylactically to reduce the frequency and intensity of attacks. In this randomized controlled trial, angioedema attack frequency and severity was reduced with lanadelumab compared with placebo over 26 weeks. Quality of life scores were also improved with lanadelumab. The most common adverse effects with lanadelumab treatment were injection site reactions and headaches.

While the use of lanadelumab for patients with hereditary angioedema is promising, the small size of the study introduced imbalances in the demographics that may represent potential confounders. In addition, the study period of only a half-year will require future follow-up to determine long-term efficacy and adverse effects.

Click to read the study in JAMA

Relevant Reading: Inhibiting plasma kallikrein for hereditary angioedema prophylaxis

In-Depth [randomized controlled trial]: In the Hereditary Angioedema Long-term Prophylaxis (HELP) trial conducted at 41 sites in Canada, Europe, Jordan, and the United States, patients who were 12 years or older with a confirmed diagnosis of hereditary angioedema types I or II were recruited to receive lanadelumab (n = 84) or placebo (n = 41). There was a 4-week run-in-period, preceded by a >= 2-week washout of any long-term prophylactic therapy, to determine baseline attack rate. Patients were randomized 2:1 to receive subcutaneously injected lanadelumab or placebo. Lanadelumab patients were assigned in a 1:1:1 ratio: 150mg every 4 weeks, 300mg every 4 weeks, or 300mg every 2 weeks. The primary endpoint was the number of attacks during the 26-week treatment period. The mean number of attacks in the placebo group was 1.97 (CI₉₅ 1.64-2.36) compared with 0.48 (CI₉₅ 0.31-0.73) in the 150mg every-4-week group, 0.53 (CI₉₅ 0.36-0.77) in the 300mg every-4-week group, and 0.26 (CI₉₅ 0.14-0.46) in the 300mg every-2-week group. Patients treated with lanadelumab had improved quality of life total scores (150-mg every-4-week group p = .047; 300-mg every-4-week group p = .07; 300-mg every-2-week group p = .001). Patients who received lanadelumab had more attack-free days (p < 0.001), reduced on-demand C1-inhibitor use (20.2% vs 65.9%; p < 0.001), and fewer moderate or severe attacks per month (p < 0.001). Most treatment-related adverse effects were mild to moderate (98.5%) and mainly comprised injection site pain (41.7%), injection site erythema (9.5%), injection site bruising (6.0%), and headache (7.1%).

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