• Cindy Leissinger, Alessandro Gringeri, Bülent Antmen, Erik Berntorp, Chiara Biasoli, Shannon Carpenter, Paolo Cortesi, Hyejin Jo, Kaan Kavakli, Riitta Lassila, Massimo Morfini, Claude Négrier, Angiola Rocino, Wolfgang Schramm, Margit Serban, Marusia Valentina Uscatescu, Jerzy Windyga, Bülent Zülfikar, and Lorenzo Mantovani.
• Louisiana Center for Bleeding and Clotting Disorders, Tulane University, New Orleans, LA, USA. cleissi@tulane.edu
• N. Engl. J. Med. 2011 Nov 3; 365 (18): 1684-92.

BackgroundPatients 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.MethodsWe 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.ResultsThirty-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.ConclusionsAICC 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.).

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