Nanofiltered C1 inhibitor concentrate for treatment of hereditary angioedema

Bruce L. Zuraw, Paula J. Busse, Martha White, Joshua Jacobs, William Lumry, James Baker, Timothy Craig, J. Andrew Grant, David Hurewitz, Leonard Bielory, William E. Cartwright, Majed Koleilat, Walter Ryan, Oren Schaefer, Michael Manning, Pragnesh Patel, Jonathan A. Bernstein, Roger A. Friedman, Robert Wilkinson, David TannerGary Kohler, Glenne Gunther, Robyn Levy, James McClellan, Joseph Redhead, David Guss, Eugene Heyman, Brent A. Blumenstein, Ira Kalfus, Michael M. Frank

Research output: Contribution to journalArticlepeer-review

394 Scopus citations

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 nano-filtered 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 angio edema 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.)

Original languageEnglish (US)
Pages (from-to)513-522
Number of pages10
JournalNew England Journal of Medicine
Volume363
Issue number6
DOIs
StatePublished - Aug 5 2010

ASJC Scopus subject areas

  • General Medicine

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