Immune Tolerance Utilizing Intermediate Purity Factor VIII Concentrate in Hemophilia A Patients with High Factor VIII Titers.

Abstract

Immune tolerance therapy (ITT) is a treatment that is used to eliminate factor VIII inhibitors associated with hemophilia A. However, standard ITT is not successful in approximately 20% of patients. In those who do not attain tolerance, the length of treatment with resultant cost of factor concentrate and family stress are major concerns. Utilization of intermediate purity products (IPP) has been suggested as a means to increase the success rate of ITT, shorten the duration of ITT, and decrease the quantity of factor concentrate used. We retrospectively analyzed outcomes for 8 patients who received IPP as part of an ITT regimen from 1993–2004. Four patients were switched from recombinant/monoclonal factor VIII to IPP during ITT because of poor response to initial therapy (Table 1). Four others were started on IPP at the initiation of ITT because they had already failed ITT or past history indicated a likelihood of failing standard ITT (Table 2). Tolerance was defined as having a Bethesda titer of <1 BU/ml, > 66% recovery of factor VIII, and/or a half-life of 6 hours or greater. In the first group, all four patients attained tolerance. In these patients the switch to IPP resulted in a faster drop in inhibitor titer than had been previously achieved. In the second group, one patient attained tolerance rapidly; one achieved partial tolerance and uses prophylactic IPP. A third patient is currently undergoing ITT and is responding well. The fourth patient has failed to achieve tolerance. These four patients had adverse risk factors that made them poor candidates for conventional ITT. Of the 6 patients who have achieved partial or complete tolerance, 4 have been switched back to recombinant factor VIII and have maintained tolerance. However, two patients have been maintained on IPP because attempts to switch to recombinant factor VIII resulted in a rise in their inhibitor titers. If tolerance can be achieved with IPP it can result in major cost savings for these patients. At our institution the cost of IPP is about 50–66% of the cost of recombinant factor VIII. These data are presented as further evidence that choice of factor may influence ITT success and that a subset of patients may benefit from an IPP regimen for ITT.Table 1: Recombinant/Monoclonal Use; Patients Switched to IPPIDAge at Inhibitor Dx (yrs)Peak Inhibitor (BU)Age at Start of ITT (yrs)Inhibitor at ITT Start (BU)Age at Switch to IPP (yrs)Reason for SwitchTime to Tolerization0016.8349.8210.0Poor response to ITT12 months0028.210011.8112.1Poor response to ITT by brother (001)6 months0055.21246.396.5–7.0 /8.2-presentPoor response to initial therapy / inability to sustain tolerization36 months0073.92703.9134.1Poor response to ITT and bleeding complications16 monthsTable 2: Patients Started on IPP InitiallyIDAge at Inhibitor Dx (yrs)Peak Inhibitor (BU)Age at Start of ITT (yrs)Inhibitor at ITT Start (BU)Time to Partial TolerizationTime to Tolerization0034.0483321.46Did not achieveNA0041.2100012.410–2029 monthsNA0061.360012.40–16 months8 months0080.82775.81.16 monthsNA