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Emicizumab Prophylaxis in Hemophilia A with Inhibitors.

Authors :
Oldenburg, Johannes
Mahlangu, Johnny N.
Kim, Benjamin
Schmitt, Christophe
Callaghan, Michael U.
Young, Guy
Santagostino, Elena
Kruse-Jarres, Rebecca
Negrier, Claude
Kessler, Craig
Valente, Nancy
Asikanius, Elina
Levy, Gallia G.
Windyga, Jerzy
Shima, Midori
Source :
New England Journal of Medicine. 8/31/2017, Vol. 377 Issue 9, p809-818. 10p.
Publication Year :
2017

Abstract

<bold>Background: </bold>Emicizumab (ACE910) bridges activated factor IX and factor X to restore the function of activated factor VIII, which is deficient in persons with hemophilia A. This phase 3, multicenter trial assessed once-weekly subcutaneous emicizumab prophylaxis in persons with hemophilia A with factor VIII inhibitors.<bold>Methods: </bold>We enrolled participants who were 12 years of age or older. Those who had previously received episodic treatment with bypassing agents were randomly assigned in a 2:1 ratio to emicizumab prophylaxis (group A) or no prophylaxis (group B). The primary end point was the difference in bleeding rates between group A and group B. Participants who had previously received prophylactic treatment with bypassing agents received emicizumab prophylaxis in group C.<bold>Results: </bold>A total of 109 male participants with hemophilia A with inhibitors were enrolled. The annualized bleeding rate was 2.9 events (95% confidence interval [CI], 1.7 to 5.0) among participants who were randomly assigned to emicizumab prophylaxis (group A, 35 participants) versus 23.3 events (95% CI, 12.3 to 43.9) among those assigned to no prophylaxis (group B, 18 participants), representing a significant difference of 87% in favor of emicizumab prophylaxis (P<0.001). A total of 22 participants in group A (63%) had zero bleeding events, as compared with 1 participant (6%) in group B. Among 24 participants in group C who had participated in a noninterventional study, emicizumab prophylaxis resulted in a bleeding rate that was significantly lower by 79% than the rate with previous bypassing-agent prophylaxis (P<0.001). Overall, 198 adverse events were reported in 103 participants receiving emicizumab prophylaxis; the most frequent events were injection-site reactions (in 15% of participants). Thrombotic microangiopathy and thrombosis were reported in 2 participants each (in the primary analysis) who had received multiple infusions of activated prothrombin complex concentrate for breakthrough bleeding. No antidrug antibodies were detected.<bold>Conclusions: </bold>Emicizumab prophylaxis was associated with a significantly lower rate of bleeding events than no prophylaxis among participants with hemophilia A with inhibitors. (Funded by F. Hoffmann-La Roche and Chugai Pharmaceutical; HAVEN 1 ClinicalTrials.gov number, NCT02622321 .). [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
00284793
Volume :
377
Issue :
9
Database :
Academic Search Index
Journal :
New England Journal of Medicine
Publication Type :
Academic Journal
Accession number :
124943448
Full Text :
https://doi.org/10.1056/NEJMoa1703068