title: Anti-inhibitor coagulant complex prophylaxis in hemophilia with inhibitors.
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<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.).
authors: Louisiana Center for Bleeding and Clotting Disorders, Tulane University, New Orleans, LA, USA. cleissi@tulane.edu
authors: Cindy
authors: C
authors: Leissinger
authors: Alessandro
authors: A
authors: Gringeri
authors: Bülent
authors: B
authors: Antmen
authors: Erik
authors: E
authors: Berntorp
authors: Chiara
authors: C
authors: Biasoli
authors: Shannon
authors: S
authors: Carpenter
authors: Paolo
authors: P
authors: Cortesi
authors: Hyejin
authors: H
authors: Jo
authors: Kaan
authors: K
authors: Kavakli
authors: Riitta
authors: R
authors: Lassila
authors: Massimo
authors: M
authors: Morfini
authors: Claude
authors: C
authors: Négrier
authors: Angiola
authors: A
authors: Rocino
authors: Wolfgang
authors: W
authors: Schramm
authors: Margit
authors: M
authors: Serban
authors: Marusia Valentina
authors: MV
authors: Uscatescu
authors: Jerzy
authors: J
authors: Windyga
authors: Bülent
authors: B
authors: Zülfikar
authors: Lorenzo
authors: L
authors: Mantovani
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001779:Blood Coagulation Factors / Q000008:administration & dosage* / Q000009:adverse effects; D002648:Child; D002675:Child, Preschool; D018592:Cross-Over Studies; D004334:Drug Administration Schedule; D005169:Factor VIII / Q000008:administration & dosage / Q000037:antagonists & inhibitors; D005260:Female; D006467:Hemophilia A / Q000150:complications / Q000188:drug therapy*; D006470:Hemorrhage / Q000517:prevention & control*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D018709:Statistics, Nonparametric; D055815:Young Adult
chemical_list: D001779:Blood Coagulation Factors; D005169:Factor VIII; C065655:anti-inhibitor coagulant complex