Icatibant, a new bradykinin-receptor antagonist, in hereditary angioedema.
BACKGROUND
Hereditary angioedema is characterized by recurrent attacks of angioedema of the skin, larynx, and gastrointestinal tract. Bradykinin is the key mediator of symptoms. Icatibant is a selective bradykinin B2 receptor antagonist.


METHODS
In two double-blind, randomized, multicenter trials, we evaluated the effect of icatibant in patients with hereditary angioedema presenting with cutaneous or abdominal attacks. In the For Angioedema Subcutaneous Treatment (FAST) 1 trial, patients received either icatibant or placebo; in FAST-2, patients received either icatibant or oral tranexamic acid, at a dose of 3 g daily for 2 days. Icatibant was given once, subcutaneously, at a dose of 30 mg. The primary end point was the median time to clinically significant relief of symptoms.


RESULTS
A total of 56 and 74 patients underwent randomization in the FAST-1 and FAST-2 trials, respectively. The primary end point was reached in 2.5 hours with icatibant versus 4.6 hours with placebo in the FAST-1 trial (P=0.14) and in 2.0 hours with icatibant versus 12.0 hours with tranexamic acid in the FAST-2 trial (P<0.001). In the FAST-1 study, 3 recipients of icatibant and 13 recipients of placebo needed treatment with rescue medication. The median time to first improvement of symptoms, as assessed by patients and by investigators, was significantly shorter with icatibant in both trials. No icatibant-related serious adverse events were reported.


CONCLUSIONS
In patients with hereditary angioedema having acute attacks, we found a significant benefit of icatibant as compared with tranexamic acid in one trial and a nonsignificant benefit of icatibant as compared with placebo in the other trial with regard to the primary end point. The early use of rescue medication may have obscured the benefit of icatibant in the placebo trial. (Funded by Jerini; ClinicalTrials.gov numbers, NCT00097695 and NCT00500656.)
Cicardi
Marco
M
Università degli Studi di Milano, Milan.
Banerji
Aleena
A
Bracho
Francisco
F
Malbrán
Alejandro
A
Rosenkranz
Bernd
B
Riedl
Marc
M
Bork
Konrad
K
Lumry
William
W
Aberer
Werner
W
Bier
Henning
H
Bas
Murat
M
Greve
Jens
J
Hoffmann
Thomas K
TK
Farkas
Henriette
H
Reshef
Avner
A
Ritchie
Bruce
B
Yang
William
W
Grabbe
Jürgen
J
Kivity
Shmuel
S
Kreuz
Wolfhart
W
Levy
Robyn J
RJ
Luger
Thomas
T
Obtulowicz
Krystyna
K
Schmid-Grendelmeier
Peter
P
Bull
Christian
C
Sitkauskiene
Brigita
B
Smith
William B
WB
Toubi
Elias
E
Werner
Sonja
S
Anné
Suresh
S
Björkander
Janne
J
Bouillet
Laurence
L
Cillari
Enrico
E
Hurewitz
David
D
Jacobson
Kraig W
KW
Katelaris
Constance H
CH
Maurer
Marcus
M
Merk
Hans
H
Bernstein
Jonathan A
JA
Feighery
Conleth
C
Floccard
Bernard
B
Gleich
Gerald
G
Hébert
Jacques
J
Kaatz
Martin
M
Keith
Paul
P
Kirkpatrick
Charles H
CH
Langton
David
D
Martin
Ludovic
L
Pichler
Christiane
C
Resnick
David
D
Wombolt
Duane
D
Fernández Romero
Diego S
DS
Zanichelli
Andrea
A
Arcoleo
Francesco
F
Knolle
Jochen
J
Kravec
Irina
I
Dong
Liying
L
Zimmermann
Jens
J
Rosen
Kimberly
K
Fan
Wing-Tze
WT
D000208:Acute Disease; D000328:Adult; D054179:Angioedemas, Hereditary / Q000188:drug therapy*; D001920:Bradykinin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D065094:Bradykinin B2 Receptor Antagonists; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007279:Injections, Subcutaneous; D057194:Intention to Treat Analysis; D008297:Male; D018709:Statistics, Nonparametric; D014148:Tranexamic Acid / Q000627:therapeutic use
D065094:Bradykinin B2 Receptor Antagonists; D014148:Tranexamic Acid; C065679:icatibant; D001920:Bradykinin
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