title: Nanofiltered C1 inhibitor concentrate for treatment of hereditary angioedema.
abstract: BACKGROUND
  Hereditary angioedema due to C1 inhibitor deficiency is characterized by recurrent acute attacks of swelling that can be painful and sometimes life-threatening.
  
  
  METHODS
  We conducted two randomized trials to evaluate nanofiltered C1 inhibitor concentrate in the management of hereditary angioedema. The first study compared nanofiltered C1 inhibitor concentrate with placebo for treatment of an acute attack of angioedema. A total of 68 subjects (35 in the C1 inhibitor group and 33 in the placebo group) were given one or two intravenous injections of the study drug (1000 units each). The primary end point was the time to the onset of unequivocal relief. The second study was a crossover trial involving 22 subjects with hereditary angioedema that compared prophylactic twice-weekly injections of nanofiltered C1 inhibitor concentrate (1000 units) with placebo during two 12-week periods. The primary end point was the number of attacks of angioedema per period, with each subject acting as his or her own control.
  
  
  RESULTS
  In the first study, the median time to the onset of unequivocal relief from an attack was 2 hours in the subjects treated with C1 inhibitor concentrate but longer than 4 hours in those given placebo (P=0.02). In the second study, the number of attacks per 12-week period was 6.26 with C1 inhibitor concentrate given as prophylaxis, as compared with 12.73 with placebo (P<0.001); the subjects who received the C1 inhibitor concentrate also had significant reductions in both the severity and the duration of attacks, in the need for open-label rescue therapy, and in the total number of days with swelling.
  
  
  CONCLUSIONS
  In subjects with hereditary angioedema, nanofiltered C1 inhibitor concentrate shortened the duration of acute attacks. When used for prophylaxis, nanofiltered C1 inhibitor concentrate reduced the frequency of acute attacks. (Funded by Lev Pharmaceuticals; ClinicalTrials.gov numbers, NCT00289211, NCT01005888, NCT00438815, and NCT00462709.)
authors.affiliation: University of California, San Diego, USA. bzuraw@ucsd.edu
authors.forename: Bruce L
authors.initials: BL
authors.lastname: Zuraw
authors.forename: Paula J
authors.initials: PJ
authors.lastname: Busse
authors.forename: Martha
authors.initials: M
authors.lastname: White
authors.forename: Joshua
authors.initials: J
authors.lastname: Jacobs
authors.forename: William
authors.initials: W
authors.lastname: Lumry
authors.forename: James
authors.initials: J
authors.lastname: Baker
authors.forename: Timothy
authors.initials: T
authors.lastname: Craig
authors.forename: J Andrew
authors.initials: JA
authors.lastname: Grant
authors.forename: David
authors.initials: D
authors.lastname: Hurewitz
authors.forename: Leonard
authors.initials: L
authors.lastname: Bielory
authors.forename: William E
authors.initials: WE
authors.lastname: Cartwright
authors.forename: Majed
authors.initials: M
authors.lastname: Koleilat
authors.forename: Walter
authors.initials: W
authors.lastname: Ryan
authors.forename: Oren
authors.initials: O
authors.lastname: Schaefer
authors.forename: Michael
authors.initials: M
authors.lastname: Manning
authors.forename: Pragnesh
authors.initials: P
authors.lastname: Patel
authors.forename: Jonathan A
authors.initials: JA
authors.lastname: Bernstein
authors.forename: Roger A
authors.initials: RA
authors.lastname: Friedman
authors.forename: Robert
authors.initials: R
authors.lastname: Wilkinson
authors.forename: David
authors.initials: D
authors.lastname: Tanner
authors.forename: Gary
authors.initials: G
authors.lastname: Kohler
authors.forename: Glenne
authors.initials: G
authors.lastname: Gunther
authors.forename: Robyn
authors.initials: R
authors.lastname: Levy
authors.forename: James
authors.initials: J
authors.lastname: McClellan
authors.forename: Joseph
authors.initials: J
authors.lastname: Redhead
authors.forename: David
authors.initials: D
authors.lastname: Guss
authors.forename: Eugene
authors.initials: E
authors.lastname: Heyman
authors.forename: Brent A
authors.initials: BA
authors.lastname: Blumenstein
authors.forename: Ira
authors.initials: I
authors.lastname: Kalfus
authors.forename: Michael M
authors.initials: MM
authors.lastname: Frank
mesh_terms: D000208:Acute Disease; D000328:Adult; D000704:Analysis of Variance; D054179:Angioedemas, Hereditary / Q000188:drug therapy* / Q000517:prevention & control*; D002648:Child; D050718:Complement C1 Inhibitor Protein / Q000009:adverse effects / Q000627:therapeutic use*; D051056:Complement Inactivating Agents / Q000009:adverse effects / Q000627:therapeutic use*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D036103:Nanotechnology; D016016:Proportional Hazards Models; D014462:Ultrafiltration
chemical_list: D050718:Complement C1 Inhibitor Protein; D051056:Complement Inactivating Agents