Use of Ecallantide in Pediatric Hereditary Angioedema

Abstract

WHAT'S KNOWN ON THIS SUBJECT:Patients with hereditary angioedema (HAE) have recurrent episodes of painful swelling. Several new therapies to prevent and treat HAE attacks are approved by the Food and Drug Administration, but their safety and efficacy in children are largely unknown.WHAT THIS STUDY ADDS: Ecallantide appears effective for treatment of HAE attacks in pediatric patients age 10 to 17 years with an acceptable safety profile. It represents a potential treatment option for adolescents with HAE. abstract OBJECTIVE: Hereditary angioedema (HAE) due to C1-inhbitor deficiency is a rare autosomal dominant disease that manifests as sudden unpredictable attacks of subcutaneous or submucosal edema affecting the skin, intestine, and upper airway. Ecallantide is a plasma kallikrein inhibitor indicated for treatment of HAE attacks in patients aged 16 years and older. This analysis examines safety and efficacy of ecallantide for treatment of HAE attacks in patients ,18 years of age.METHODS: Data for patients aged 9 to 17 years treated subcutaneously with 30 mg ecallantide or placebo were pooled from 4 clinical studies (2 double-blind, placebo-controlled and 2 open-label). Efficacy end points included 2 HAE-specific patient-reported outcome measures: mean symptom complex severity (MSCS) score and treatment outcome score (TOS). Times to initial improvement, sustained improvement, and complete or near-complete symptom resolution were calculated. Treatment-emergent adverse events were examined. RESULTS:Overall, 29 pediatric patients were included; 25 of them received ecallantide for 62 total HAE attacks, and 10 received placebo for 10 total attacks. Ecallantide-treated attacks revealed clinically relevant reduction in symptom severity at 4 hours postdosing based on mean change in MSCS score (21.4 6 0.9 ecallantide versus 20.9 6 0.6 placebo) and TOS (73.9 6 35.50 ecallantide versus 45.0 6 43.78 placebo). Patients treated with ecallantide showed rapid improvement in symptoms (median time to complete or near-complete symptom resolution: 181 minutes). No serious adverse events related to treatment were observed.CONCLUSIONS: Ecallantide appears effective for HAE attacks in adolescents, with rapid symptom improvement. No unexpected safety issues were identified. Pediatrics 2013;132:e490-e497 AUTHORS:

Recombinant human C1 esterase inhibitor treatment for hereditary angioedema attacks in children

“…A systematic review of pdC1‐INH for HAE attacks in pediatrics, including children less than 12 years of age, reported efficacy and safety results similar to those observed in adults . Ecallantide, a plasma kallikrein inhibitor indicated for acute treatment in patients who are at least 12 years of age, exhibited a safety and efficacy profile similar to that observed in adults with HAE. Results of an open‐label, phase 3 study of icatibant reported efficacy and tolerability of this bradykinin B2 receptor antagonist for acute treatment of C1‐INH‐HAE in pediatric patients (inclusion criteria, aged 2‐17 years) .…”

Management of Children With Hereditary Angioedema Due to C1 Inhibitor Deficiency

“…A recent analysis of pooled data suggests that ecallantide is effective for the treatment of HAE attacks in younger patients and has an acceptable safety profile. 40,41 Ecallantide has been associated with hypersensitivity reactions in a small percentage (3%-4%) of recipients and therefore has a boxed warning that states that it must be administered under the supervision of medical personnel. It can often be arranged for a home health nurse to administer the drug.…”

How we manage persons with hereditary angioedema

“…The limited uncontrolled experience with their use in younger age groups has been recently reviewed (Wahn et al, 2012;Kuhlen & Banerji, 2015). There is open-label data showing the safety and efficacy of pdC1INH (Lumry et al, 2013b;Schneider et al, 2013), rhC1INH and ecallantide (MacGinnitie et al, 2013). Trials are on-going for many of the existing drugs to guide future treatment options.…”