Inhibitor Development in Previously Untreated or Minimally Treated Patients with Hemophilia a Treated with a Plasma-derived Solvent-detergent Factor VIII Concentrate

Abstract number: P1415

Mara¹ SM, Alessandro² G, Giuseppe T, Antonio FS

¹¹Center of Pharmacoeconomics, Department of Pharmacological Sciences, University of Milan, Italy ²²Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, IRCCS Maggiore Hospital and University of Milan, Italy

Background:  A solvent-detergent virus-inactivated plasma-derived FVIII concentrate has been introduced in the treatment of Italian patients with hemophilia A since 15 years ago. This product is a non-monoclonally purified, high purity FVIII concentrate, without albumin in the final formulation and without removal of its VWF content.

Methods:  A retrospective survey was carried out in Italy with an electronic form in order to evaluate the immunogenicity of a solvent-detergent virus-inactivated plasma-derived FVIII concentrate in previously untreated patients (PUPs) never exposed to other concentrates or in minimally treated patients (MTPs) previously exposed for up to 5 days to other concentrates.

Results:  The investigated population was represented by 99 patients (71 of them, 72%, with FVIII < 1%, and 28 patients, 28%, with FVIII from 1 to 5%) with ages ranging from 6 to 64 years (mean = 36.33, median = 21.35) of whom 31 (31%) PUPs and 68 (69%) MTPs, with 1 to 5 exposure days (EDs) to other plasma products (median = 4). Surveyed patients had been exposed to a solvent-detergent virus-inactivated plasma-derived FVIII concentrate for 21 to 1580 EDs (mean = 284 and median = 88). Seven patients (3 PUPs and 4 MTPs) developed inhibitors (7.1%, CI 95% 3–14%) after 4 to 22 EDs (median = 11.5, mean = 12.3). All of these inhibitor patients were severe. Of these, 5 were low responders (less than 5 BU/ml) and 2 were high responders (peak inhibitor titer 99 and 127 U/ml respectively). Two low responders cleared inhibitors spontaneously; one high responder underwent immunotolerance treatment with complete and stable response.

Conclusions:  These findings suggest that the solvent-detergent plasma-derived FVIII concentrate that has been used in Italy for 15 years is at low risk of inhibitor development in PUPs and MTPs with severe and moderate hemophilia. Moreover, the risk of inhibitor development was similar to that reported for other plasma-derived VWF-containing FVIII products.