Hypothesis: The mechanism of recurrent hemarthroses (joint bleeds) resulted from chronic synovitis of target joints in hemophilic patients is thought to be a VEGF-based neo-angiogenic process. Local anti-VEGF therapy with intra-articular bevacizumab (Avastin), a VEGF-neutralizing monoclonal antibody that can efficiently antagonize VEGF activity, may block the process and decrease the frequency of recurrent bleeding episodes. In addition, we proved that intra-articular injection of bevacizumab in rat model is safe without significant local or systemic adverse events.~Primary Objective The efficacy of intra-articular bevacizumab injection for secondary prevention of recurrent hemarthroses for hemophilia patients who has had target joints with chronic synovitis. The safety profiles of intra-articular bevacizumab injection for hemophilia patients.~Study Population Adult hemophilia patients who have had one or more target joints with chronic synovitis and recurrent hemarthroses.~Investigational therapy: Intra-articular injection of Bevacizumab (20 or 40 mg/ 0.8 or 1.6 ml/ dose) every month (28 days) for up to 4 months, depending on the improvement of target joint bleeding.~Study Design The estimated study period is between Jan 2014 and Dec 2015. Totally 10 joints will be enrolled for this pilot study. Before enrollment, the joint(s) will be evaluated for their severity both clinically (by 10-point Pain Score, range of motion for the target joint, and World Federation of Hemophilia Score) and by MRI (using the compatible MRI scales developed by International Prophylaxis Study Group [IPSG]). Intra-articular injection of bevacizumab will be administered, after prophylactic factor supplementation, every month for up to four injections. In the first four patients, 20mg of bevacizumab will be administered. If there are no Gr 3 or Gr4 dose-limiting toxicities, bevacizumab dose will be escalated to 40mg in the other 6 patients. Before every procedure, the plasma and the synovial fluid samples will be collected for VEGF quantification for the correlative biomarker study. After completing the protocol treatment, the efficacy parameters as well as the safety profiles will be evaluated.~Assessments The efficacy: the differences of total episodes of recurrent hemarthroses within 3 months before and after completing bevacizumab intra-articular injection. Post-procedure target joints bleedings will be recorded at intervals of 1st, 3rd, 6th, and 12th months. The total absence of haemarthrosis (zero bleeding) is rated as excellent response; bleeding reduction between 75% and 99% is rated good, between 50% and 74% as fair, and below 50% as poor.
Primary Objective The efficacy of intra-articular bevacizumab injection for secondary prevention of recurrent hemarthroses for hemophilia patients who has had target joints with chronic synovitis. The safety profiles of intra-articular bevacizumab injection for hemophilia patients.~Study Population Adult hemophilia patients who have had one or more target joints with chronic synovitis and recurrent hemarthroses.~Investigational therapy: Intra-articular injection of Bevacizumab (20 or 40 mg/ 0.8 or 1.6 ml/ dose) every month (28 days) for up to 4 months, depending on the improvement of target joint bleeding.~Study Design The estimated study period is between Jan 2014 and Dec 2015. Totally 10 joints will be enrolled for this pilot study. Before enrollment, the joint(s) will be evaluated for their severity both clinically (by 10-point Pain Score, range of motion for the target joint, and World Federation of Hemophilia Score) and by MRI (using the compatible MRI scales developed by International Prophylaxis Study Group [IPSG]). Intra-articular injection of bevacizumab will be administered, after prophylactic factor supplementation, every month for up to four injections. In the first four patients, 20mg of bevacizumab will be administered. If there are no Gr 3 or Gr4 dose-limiting toxicities, bevacizumab dose will be escalated to 40mg in the other 6 patients. Before every procedure, the plasma and the synovial fluid samples will be collected for VEGF quantification for the correlative biomarker study. After completing the protocol treatment, the efficacy parameters as well as the safety profiles will be evaluated.