Efficacy and safety of recombinant human C1-inhibitor for the treatment of attacks of hereditary angioedema: European open-label extension study.
BACKGROUND
Hereditary angioedema (HAE) owing to C1 inhibitor deficiency is an autosomal dominant disorder, characterized by recurrent, potentially life-threatening, localized attacks of tissue swelling. Current treatment involves the infusion of C1 inhibitor protein (C1-INH) isolated from human plasma.


OBJECTIVE
This open-label extension to a European, Israeli and Argentinean randomized study (NCT00262301) aimed to investigate the efficacy and safety of recombinant human C1 inhibitor (rhC1-INH) as a first-line treatment following an HAE attack, together with its effect on subsequent attacks.


METHODS
An HAE-specific visual analogue scale (VAS) 0-100 mm was used by patients to assess the severity of attack at four anatomical locations. Patients were treated with one, single-vial, fixed-dose of rhC1-INH (2100 U), followed by up to two further vials at the investigators discretion. The primary end-point was the time from first rhC1-INH injection to first onset of relief of symptoms (≥ 20 mm decrease on VAS). Response to treatment was defined as the onset of relief within 4 h.


RESULTS
A total of 57 patients were treated for 194 HAE attacks. Overall, sustained relief of symptoms was achieved in 87% of rhC1-INH-treated patients within 4 h of treatment, with 57% of attacks requiring only one vial of rhC1-INH. When categorized by successive attacks experienced by individual patients, the response rate to rhC1-INH treatment was 96%, 83%, 87%, 80% and 80% for attacks 1-5 respectively. Treatment with rhC1-INH was well tolerated, with no discontinuations owing to treatment-emergent adverse events and no adverse events relating to immunogenicity.


CONCLUSIONS
Treatment with rhC1-INH provides fast-onset relief for an HAE attack, with a high rate of therapeutic response maintained throughout subsequent attacks.
Department of Allergology-Immunology, Mures County Hospital, University of Medicine and Pharmacy, Tîrgu-Mureş, Romania. moldovan.dumitru@gmail.com
D
D
Moldovan
A
A
Reshef
J
J
Fabiani
S
S
Kivity
E
E
Toubi
M
M
Shlesinger
M
M
Triggiani
V
V
Montinaro
E
E
Cillari
G
G
Realdi
M
M
Cancian
S
S
Visscher
A
A
Zanichelli
A
A
Relan
M
M
Cicardi
D000293:Adolescent; D000328:Adult; D000368:Aged; D054179:Angioedemas, Hereditary / Q000188:drug therapy*; 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*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins / Q000627:therapeutic use; D012307:Risk Factors; D016896:Treatment Outcome; D055815:Young Adult
D050718:Complement C1 Inhibitor Protein; D051056:Complement Inactivating Agents; D011994:Recombinant Proteins