Response to ecallantide treatment of acute attacks of hereditary angioedema based on time to intervention: Results from the EDEMA clinical trials

Abstract

Hereditary Angioedema (HAE) is a rare, debilitating, genetic disorder characterized by acute attacks of edema without urticaria. Ecallantide, a direct plasma kallikrein inhibitor, is approved for treatment of acute HAE attacks. This article addresses the efficacy of ecallantide in the treatment of moderate-to-severe attacks of HAE based on time to treatment. A post hoc integrated analysis of the EDEMA4 and EDEMA3-DB clinical trials was performed based on the time to patient's treatment, defined as the time from initial recognition of moderate-to-severe symptoms to dosing (cohort, 0-2, >2-4, >4-6, >6-8, and >8 hours). Mean symptom complex severity (MSCS) score and treatment outcome score (TOS) were analyzed. Complete or near-complete resolution of symptoms was assessed at 4 and 24 hours. In this analysis, 70 patients received 30 mg of subcutaneous (s.c.) ecallantide and 73 patients received placebo. Change from baseline in MSCS score and TOS at 4 hours revealed significantly better response to ecallantide versus placebo for patients treated >2-4 (n = 46; p = 0.002; p = 0.003) or >4-6 (n = 47; p = 0.044; p = 0.043) hours after symptom onset. Fewer patients were treated within 2 hours of symptom onset; for these patients (n = 10; p = 0.752; p = 0.422) treatment did not achieve statistical significance. For overall response, complete or near-complete resolution was greatest within the 0- to 2-hour cohort (71.4%). As with other therapies for HAE early ecallantide therapy is optimal. Treatment with ecallantide within 6 hours of symptom onset leads to more rapid and sustained improvement of symptoms.

The international WAO/EAACI guideline for the management of hereditary angioedema—The 2017 revision and update

“…Early treatment with C1‐INH concentrate, ecallantide, or icatibant provides a better treatment response than late treatment. Early treatment is associated with a shorter time to resolution of symptoms and shorter total attack duration regardless of attack severity . As early treatment is facilitated by self‐administration, all patients with HAE‐1/2 should be considered for home therapy and self‐administration training .…”

Update on treatment of hereditary angioedema

“…Patients in this trial reported a mean decrease of symptom score at 4 h of 0.81 on Ecallantide vs. 0.37 on placebo (P = 0.01) [35]. A post hoc integrated analysis of the EDEMA4 and EDEMA3 clinical trials showed that change from baseline in MSCS and TOS was significantly better with ecallantide vs. placebo for patients treated > 2-4 h after symptom onset (n = 46, P = 0.002, P = 0.003) and > 4-6 h after onset of symptoms (n = 47, P = 0.044, P = 0.043) [36].…”

An analysis of the teaching of intravenous self-administration in patients with hereditary angio-oedema

“…HAE attack treatments are most effective when administered early. [5][6][7] Although patients are dependent upon ª 2016 British Association of Dermatologists healthcare providers for the administration of ondemand treatment, many have reported not seeking treatment in a hospital as a result of previous inappropriate treatment, e.g. for histamine-induced angiooedema.…”

“…Treatment is most effective when administered early in the course of an HAE attack . Home‐based self‐administration of C1 inhibitor or icatibant for the on‐demand treatment of attacks reduces attack duration and treatment‐associated costs .…”

“…1 Treatment is most effective when administered early in the course of an HAE attack. [5][6][7] Home-based selfadministration of C1 inhibitor or icatibant for the ondemand treatment of attacks reduces attack duration and treatment-associated costs. [6][7][8][9] Recent survey data indicate that in the EU, Canada and the USA, there are several barriers to the uptake of self-administration of HAE treatments, including fears regarding venous access/condition or self-injection, competence and safety.…”