rfviia总剂量.ppt

Role of gene haplotypes in inhibitor development Rates of inhibitor development in PUPs with plasma-derived factor (SIPPET) Inhibitor rates with long-acting factors * * * * * * This figure illustrates the frequencies (counts) of efficacy outcomes by time point and type of treatment. There were no statistically significant differences in the distribution of outcomes by treatment at any time point. The primary endpoint of equivalence was not met. Astermark J et al. A randomized comparison of bypassing agents in hemophilia complicated by an inhibitor: the FEIBA NovoSeven Comparative (FENOC) Study. Blood. 2007;109:546-551. * * * * * * * * * * * * * * There is no consensus for the optimal regimen, as they have not been systematically compared. They may differ more in time to success rather than in the overall success rate. * Failure to demonstrate a progressive 20% reduction in inhibitor titer over each successive 6-month period of uninterrupted ITI, beginning 3 months after initiation to allow for expected anamnesis * Occur in 3% of patients Approximately 80% are high-responding Frequent occurrence of allergic/anaphylactic reactions prior to or simultaneously with the onset of inhibitors Antibodies to FIX protein IgG4 and IgG1 subclasses Focus on patients with FIX inhibitor-related complications (severe allergic or anaphylactic reactions) Median age at inhibitor detection: 19.5 months (9-156) Median exposure days to FIX replacement therapy: 11 days (2-180) Mean peak inhibitor titer: 30 BU (1-1156) * A rigorous definition of success requires that there be no inhibitor detectable by Bethesda assay and that the in vivo recovery of FVIII must be normal. After achieving immune tolerance, patients are often placed on a continuous prophylactic FVIII schedule. The International Registry is maintained by Dr. G. Mariani, University of Palermo, Italy. The North American registry is maintained by Dr. D. DiMichele, Columbia University, New York. No singl