Safety and efficacy of prophylactic nanofiltered C1-inhibitor in hereditary angioedema.
OBJECTIVE
Nanofiltered C1-inhibitor (C1INH-nf) is approved for prophylactic treatment of hereditary angioedema. This study assessed the efficacy and safety of C1INH-nf as prophylactic therapy in a large cohort of patients with hereditary angioedema.


METHODS
An open-label multicenter extension study was performed involving 146 subjects with hereditary angioedema who were treated with C1INH-nf for up to 2.6 years in centers throughout the United States. Subjects were to be treated with C1INH-nf 1000 units every 3 to 7 days. The primary efficacy variable was the number of attacks of angioedema experienced.


RESULTS
Subjects experienced a 93.7% reduction in attacks while taking prophylactic C1INH-nf (0.19 attacks per month; interquartile range, 0.00-0.64) compared with the historical rate of attacks. Some 87.7% reported an attack frequency of 1 or less attack per month during prophylactic C1INH-nf and 34.9% had no attacks during the study. Some 7.5% of subjects experienced relatively frequent attacks despite twice-weekly C1INH-nf. Although twice-weekly dosing was highly effective in most subjects, once-weekly dosing provided adequate control in a subgroup of subjects. No clinical characteristics predicted the response to prophylactic C1INH-nf, including historical attack frequency. C1INH-nf was well tolerated.


CONCLUSIONS
Prophylactic C1INH-nf is highly effective and safe, and provides durable prophylaxis in the majority of patients with hereditary angioedema. The recommended dose of C1INH-nf 1000 units twice weekly is supported by this open-label study. Individual patients may benefit from further dose adjustment on the basis of response to therapy and individual treatment goals.
University of California, San Diego, La Jolla, USA. bzuraw@ucsd.edu
Bruce L
BL
Zuraw
Ira
I
Kalfus
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D054179:Angioedemas, Hereditary / Q000150:complications* / Q000188:drug therapy / Q000517:prevention & control*; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D003174:Complement C1 Inactivator Proteins / Q000008:administration & dosage* / Q000009:adverse effects*; D050718:Complement C1 Inhibitor Protein; D004334:Drug Administration Schedule; D005260:Female; D005374:Filtration; D006801:Humans; D008297:Male; D008875:Middle Aged; D036103:Nanotechnology; D010146:Pain / Q000188:drug therapy / Q000209:etiology / Q000517:prevention & control*; D010147:Pain Measurement; D011994:Recombinant Proteins / Q000008:administration & dosage* / Q000009:adverse effects*; D016896:Treatment Outcome
D003174:Complement C1 Inactivator Proteins; D050718:Complement C1 Inhibitor Protein; D011994:Recombinant Proteins; C469952:SERPING1 protein, human