TY - JOUR
T1 - Anti-Inhibitor Coagulant Complex Prophylaxis in Hemophilia with Inhibitors
AU - Leissinger, Cindy
AU - Gringeri, Alessandro
AU - Antmen, Bulent
AU - Berntorp, Erik
AU - Biasoli, Chiara
AU - Carpenter, Shannon
AU - Cortesi, Paolo
AU - Jo, Hyejin
AU - Kavakli, Kaan
AU - Lassila, Riitta
AU - Morfini, Massimo
AU - Negrier, Claude
AU - Rocino, Angiola
AU - Schramm, Wolfgang
AU - Serban, Margit
AU - Uscatescu, Marusia Valentina
AU - Windyga, Jerzy
AU - Zulfikar, Bulent
AU - Mantovani, Lorenzo
PY - 2011
Y1 - 2011
N2 - 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.)
AB - 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.)
U2 - 10.1056/NEJMoa1104435
DO - 10.1056/NEJMoa1104435
M3 - Article
C2 - 22047559
SN - 0028-4793
VL - 365
SP - 1684
EP - 1692
JO - New England Journal of Medicine
JF - New England Journal of Medicine
IS - 18
ER -