Response time for ecallantide treatment of acute hereditary angioedema attacks.
BACKGROUND
Hereditary angioedema (HAE) is a rare, debilitating, and potentially fatal disease characterized by acute attacks of swelling that can affect the abdomen/gastrointestinal tract, larynx, face, genitals, and extremities. Ecallantide is a novel plasma kallikrein inhibitor developed for the treatment of acute HAE attacks.


OBJECTIVE
To examine the speed of effect of ecallantide vs placebo.


METHODS
Data were integrated from 2 randomized, double-blind, placebo-controlled phase 3 trials of ecallantide in patients with HAE. Eligible patients presented within 8 hours of onset of a moderate to severe HAE attack for 1:1 randomization to receive a single dose of 30 mg of subcutaneous ecallantide or placebo. End points included time to beginning of improvement, time to sustained overall improvement, and time to significant overall improvement.


RESULTS
A total of 143 participants (70 receiving ecallantide and 73 receiving placebo) were included. The distribution curves for time to beginning of improvement demonstrated a trend in favor of ecallantide vs placebo within 4 hours (P(log rank) = .09). For time to onset of sustained improvement, the difference in the distribution of the curves between the 2 groups reached significance by 2 hours after dosing (P(log rank) = .04). For time to significant overall improvement, the difference in the distribution of the curves reached significance in favor of ecallantide by 90 minutes (P(log rank) = .04). The beneficial effect of ecallantide was demonstrated earliest for abdominal attacks, followed by laryngeal and peripheral attacks.


CONCLUSIONS
Ecallantide provides relief of acute HAE attack symptoms, with rapidity of response commensurate with therapeutic needs for HAE attack locations.
University of California at Los Angeles, David Geffen School of Medicine, Los Angeles, California 90095-1680, USA. mriedl@mednet.ucla.edu
Marc
M
Riedl
Marilyn
M
Campion
Patrick T
PT
Horn
William E
WE
Pullman
D000293:Adolescent; D000328:Adult; D000368:Aged; D054179:Angioedemas, Hereditary / Q000188:drug therapy*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007279:Injections, Subcutaneous; D007610:Kallikreins / Q000037:antagonists & inhibitors*; D008297:Male; D008875:Middle Aged; D015337:Multicenter Studies as Topic; D010455:Peptides / Q000008:administration & dosage / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic; D013997:Time Factors; D016896:Treatment Outcome; D014481:United States
D010455:Peptides; C511194:ecallantide; D007610:Kallikreins