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Anti-Inhibitor Coagulant Complex Prophylaxis in Hemophilia with Inhibitors

Leissinger, Cindy; Gringeri, Alessandro; Antmen, Bulent; Berntorp, Erik LU ; Biasoli, Chiara; Carpenter, Shannon; Cortesi, Paolo; Jo, Hyejin; Kavakli, Kaan and Lassila, Riitta, et al. (2011) In New England Journal of Medicine 365(18). p.1684-1692
Abstract
Background Patients with severe hemophilia A and factor VIII inhibitors are at increased risk for serious bleeding complications and progression to end-stage joint disease. Effective strategies to prevent bleeding in such patients have not yet been established. Methods We enrolled patients with hemophilia A who were older than 2 years of age, had high-titer inhibitors, and used concentrates known as bypassing agents for bleeding in a prospective, randomized, crossover study comparing 6 months of anti-inhibitor coagulant complex (AICC), infused prophylactically at a target dose of 85 U per kilogram of body weight (+/- 15%) on 3 nonconsecutive days per week, with 6 months of on-demand therapy (AICC at a target dose of 85 U per kilogram [+/-... (More)
Background Patients with severe hemophilia A and factor VIII inhibitors are at increased risk for serious bleeding complications and progression to end-stage joint disease. Effective strategies to prevent bleeding in such patients have not yet been established. Methods We enrolled patients with hemophilia A who were older than 2 years of age, had high-titer inhibitors, and used concentrates known as bypassing agents for bleeding in a prospective, randomized, crossover study comparing 6 months of anti-inhibitor coagulant complex (AICC), infused prophylactically at a target dose of 85 U per kilogram of body weight (+/- 15%) on 3 nonconsecutive days per week, with 6 months of on-demand therapy (AICC at a target dose of 85 U per kilogram [+/- 15%] used for bleeding episodes). The two treatment periods were separated by a 3-month washout period, during which patients received on-demand therapy for bleeding. The primary outcome was the number of bleeding episodes during each 6-month treatment period. Results Thirty-four patients underwent randomization; 26 patients completed both treatment periods and could be evaluated per protocol for the efficacy analysis. As compared with on-demand therapy, prophylaxis was associated with a 62% reduction in all bleeding episodes (P < 0.001), a 61% reduction in hemarthroses (P < 0.001), and a 72% reduction in target-joint bleeding (>= 3 hemarthroses in a single joint during a 6-month treatment period) (P < 0.001). Thirty-three randomly assigned patients received at least one infusion of the study drug and were evaluated for safety. One patient had an allergic reaction to the study drug. Conclusions AICC prophylaxis at the dosage evaluated significantly and safely decreased the frequency of joint and other bleeding events in patients with severe hemophilia A and factor VIII inhibitors. (Funded by Baxter BioScience; Pro-FEIBA ClinicalTrials.gov number, NCT00221195.) (Less)
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published
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in
New England Journal of Medicine
volume
365
issue
18
pages
1684 - 1692
publisher
Massachusetts Medical Society
external identifiers
  • wos:000296424200007
  • scopus:80455144639
ISSN
0028-4793
DOI
10.1056/NEJMoa1104435
language
English
LU publication?
yes
id
3151dbcd-bf42-4232-8aa0-f2b8a30ec2f5 (old id 2207706)
date added to LUP
2011-11-30 09:12:32
date last changed
2017-11-05 03:10:08
@article{3151dbcd-bf42-4232-8aa0-f2b8a30ec2f5,
  abstract     = {Background Patients with severe hemophilia A and factor VIII inhibitors are at increased risk for serious bleeding complications and progression to end-stage joint disease. Effective strategies to prevent bleeding in such patients have not yet been established. Methods We enrolled patients with hemophilia A who were older than 2 years of age, had high-titer inhibitors, and used concentrates known as bypassing agents for bleeding in a prospective, randomized, crossover study comparing 6 months of anti-inhibitor coagulant complex (AICC), infused prophylactically at a target dose of 85 U per kilogram of body weight (+/- 15%) on 3 nonconsecutive days per week, with 6 months of on-demand therapy (AICC at a target dose of 85 U per kilogram [+/- 15%] used for bleeding episodes). The two treatment periods were separated by a 3-month washout period, during which patients received on-demand therapy for bleeding. The primary outcome was the number of bleeding episodes during each 6-month treatment period. Results Thirty-four patients underwent randomization; 26 patients completed both treatment periods and could be evaluated per protocol for the efficacy analysis. As compared with on-demand therapy, prophylaxis was associated with a 62% reduction in all bleeding episodes (P &lt; 0.001), a 61% reduction in hemarthroses (P &lt; 0.001), and a 72% reduction in target-joint bleeding (&gt;= 3 hemarthroses in a single joint during a 6-month treatment period) (P &lt; 0.001). Thirty-three randomly assigned patients received at least one infusion of the study drug and were evaluated for safety. One patient had an allergic reaction to the study drug. Conclusions AICC prophylaxis at the dosage evaluated significantly and safely decreased the frequency of joint and other bleeding events in patients with severe hemophilia A and factor VIII inhibitors. (Funded by Baxter BioScience; Pro-FEIBA ClinicalTrials.gov number, NCT00221195.)},
  author       = {Leissinger, Cindy and Gringeri, Alessandro and Antmen, Bulent and Berntorp, Erik and Biasoli, Chiara and Carpenter, Shannon and Cortesi, Paolo and Jo, Hyejin and Kavakli, Kaan and Lassila, Riitta and Morfini, Massimo and Negrier, Claude and Rocino, Angiola and Schramm, Wolfgang and Serban, Margit and Uscatescu, Marusia Valentina and Windyga, Jerzy and Zulfikar, Bulent and Mantovani, Lorenzo},
  issn         = {0028-4793},
  language     = {eng},
  number       = {18},
  pages        = {1684--1692},
  publisher    = {Massachusetts Medical Society},
  series       = {New England Journal of Medicine},
  title        = {Anti-Inhibitor Coagulant Complex Prophylaxis in Hemophilia with Inhibitors},
  url          = {http://dx.doi.org/10.1056/NEJMoa1104435},
  volume       = {365},
  year         = {2011},
}