OBJECTIVES : Hereditary angioedema (HAE) is a rare disorder characterized by recurrent episodes of body tissue swelling. We evaluated the cost-effectiveness of lanadelumab and the C1-inhibitors, Cinryze and Haegarda, for long-term prophylaxis against acute HAE attacks versus no prophylaxis in adult patients with HAE type 1/2 from a US health system perspective.

METHODS : We developed a Markov model with two health states: alive with HAE and dead with monthly cycles over a life-time horizon. Baseline characteristics were: mean age of 39.6 years, 68.4% female, mean weights of 88.8kg (male) and 76.4 kg (female), and a baseline attack rate of 3.39 per month. We tracked number of attacks, time attack free, survival, quality-of-life, and costs. Parameters were obtained from publicly available databases, published literature, and expert opinion. Outcomes included discounted (3% per year) quality-adjusted life-years (QALYs) and costs (2018 US$), and incremental cost per QALY gained (ICER). We conducted univariate and probabilistic sensitivity analyses, and scenario analyses.

RESULTS : Expected QALYs were 17.47 for no prophylaxis, and ranged from 18.21 (Cinryze) to 18.66 (lanadelumab) for patients receiving prophylaxis. Expected costs were $9,953,000 for no prophylaxis and ranged from $10,343,000 (Haegarda) to $14,396,000 (Cinryze) yielding ICERs ranging from $328,000 (Haegarda) to $5,954,000 (Cinryze). ICERs were extremely sensitive to drug acquisition costs, the baseline attack rate and treatment effects. The probability that Haegarda and lanadelumab were cost-effective at a $150,000/QALY threshold was 36% and 5%, respectively. A scenario analysis showed that 75% of patients would need to be switched to every four-week dosing for lanadelumab to be cost-effective at a $150,000/QALY threshold.

CONCLUSIONS : In the base case, drugs for prophylaxis against acute attacks of HAE were likely to exceed the cost-effectiveness threshold of $150,000/QALY. However, the model outcomes were highly sensitive to changes in model inputs and assumptions and should be interpreted with caution.