OBJECTIVES: Hereditary angioedema (HAE) is a rare inherited disease with unpredictable attacks of anywhere in body including larynx, which can be fatal. The purpose of this systematic review was to compare the efficacy and safety of currently available medications for the treatment of acute attack of HAE.

METHODS: A systematic search was conducted using MEDLINE and The Cochrane Library from January 2003 through June 2018. To be included, studies had to evaluate the efficacy and safety of the medications that could be used to treat acute attack of HAE. Then, we performed indirect treatment comparison of the efficacy using ‘time to onset of symptom relief (hours)’ as outcome measure with placebo or supportive care as a common control group. The random effect model was applied to meta-analysis because of the heterogeneity of studies included. The safety profile of the included studies reported different measures, therefore we performed qualitative synthesis.

RESULTS: A total of 230 studies that investigated treatment for HAE were identified. Seven placebo-controlled studies among three medication groups (ecallantide, icatibant, C1-INH concentrate) for the treatment of acute attack were included network meta-analysis. All of medications were generally tolerable in the clinical studies. Each of the medications showed a statistically significant early onset of symptom relief compared with the control group; icatibant (mean difference, MD -8.93, p=0.03), C1-INH (MD -2.74, p=0.002), and ecallantide (MD -1.63, p=0.003). However, there were no statistically significant superiority of efficacy among the medications in each pair of indirect comparison.

CONCLUSIONS: Currently, available treatments generally have good efficacy and tolerability compared to placebo, but no relative superiority among treatments can be found. However, because of the nature of such a rare disease, all of the included studies had a relatively small number of patients, therefore further studies are needed to identify the relative efficacy and cost-effectiveness of these treatments.