Efficacy of human C1 esterase inhibitor concentrate compared with placebo in acute hereditary angioedema attacks.
BACKGROUND
Hereditary angioedema caused by C1 esterase inhibitor deficiency is a rare disorder.


OBJECTIVE
To compare the efficacy of pasteurized C1 esterase inhibitor concentrate (Berinert, CSL Behring) at intravenous doses of 10 or 20 U/kg body weight with placebo in the treatment of single, acute abdominal or facial attacks in patients with hereditary angioedema.


METHODS
This was a randomized, double-blind, placebo-controlled study in 125 patients with type I or II hereditary angioedema. The primary outcome was time from start of treatment to onset of symptom relief. Secondary outcomes were time to complete resolution, proportion of patients with worsened intensity of angioedema symptoms between 2 and 4hours after treatment, and number of vomiting episodes within 4 hours.


RESULTS
Median time to onset of relief was significantly shorter with C1 esterase inhibitor concentrate at a dose of 20 U/kg than with placebo (0.5 vs 1.5 hours; P = .0025), whereas with 10 U/kg, the time to onset of relief was only slightly shorter than with placebo (1.2 vs 1.5 hours; P = .2731). Compared with placebo, the reduction in time to onset of relief was greatest for severe attacks (0.5 vs 13.5 hours). The secondary outcomes consistently supported the efficacy of the 20 U/kg dose. C1 esterase inhibitor concentrate was safe and well tolerated. No seroconversions were observed for HIV, hepatitis virus, or human B19 virus.


CONCLUSIONS
C1 esterase inhibitor concentrate given intravenously at a dose of 20 U/kg is an effective and safe treatment for acute abdominal and facial attacks in patients with hereditary angioedema, with a rapid onset of relief.
Craig
Timothy J
TJ
Penn State University College of Medicine, Hershey, Pa., USA.
Levy
Robyn J
RJ
Wasserman
Richard L
RL
Bewtra
Againdra K
AK
Hurewitz
David
D
Obtułowicz
Krystyna
K
Reshef
Avner
A
Ritchie
Bruce
B
Moldovan
Dumitru
D
Shirov
Todor
T
Grivcheva-Panovska
Vesna
V
Kiessling
Peter C
PC
Keinecke
Heinz-Otto
HO
Bernstein
Jonathan A
JA
D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D054179:Angioedemas, Hereditary / Q000188:drug therapy*; D002648:Child; D050718:Complement C1 Inhibitor Protein / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D051056:Complement Inactivating Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007275:Injections, Intravenous; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D055815:Young Adult
D050718:Complement C1 Inhibitor Protein; D051056:Complement Inactivating Agents