Cross‐reacting inhibitors against recombinant porcine factor VIII in acquired hemophilia A: Data from the GTH ‐ AH 01/2010 Study

Background Recombinant porcine factor VIII (rp FVIII , OBI ‐1, susoctocog alfa) is used for the treatment of acute bleeds in patients with acquired hemophilia A ( AHA ). Inhibitors in AHA can sometimes cross‐react with rp FVIII . Objectives To assess the frequency, strength, and determinants of cross‐reactivity. Patients/methods Baseline samples from 70 patients of the prospective, observational cohort study GTH ‐ AH 01/2010 were assessed for anti‐human FVIII and anti‐rp FVIII inhibitors using modified Nijmegen‐Bethesda assays, as well as anti‐human FVIII domain reactivity using enzyme‐linked immunoassay (ELISA) . Results Anti‐human FVIII inhibitors were present in all samples ranging between 0.7 and 3891 Bethesda Units (BU)/mL. Inhibitors from 31 of 70 patients (44%) partially inhibited rp FVIII with anti‐rp FVIII titers ranging between 0.5 and 471 BU/mL. Anti‐rp FVIII titers were ≤5 BU in most patients. Patients with cross‐reacting inhibitors, as compared to patients without, had significantly higher anti‐human FVIII titers (27.8 versus 5.4 BU/mL) and lower baseline FVIII activity (<1 versus 2.6 IU/dL). The ratio between anti‐rp FVIII to anti‐human titers was highest for inhibitors involving the C1 domain. Cross‐reactivity was very rare, if inhibitors reacted only with the C2 domain of FVIII (6%). An anti‐human FVIII titer of >100 BU/mL predicted cross‐reactivity with 97% likelihood, whereas an anti‐human FVIII titer of <3.8 BU/mL predicted absent cross‐reactivity with 90% likelihood. Conclusion Cross‐reacting inhibitors should be considered when choosing a treatment for bleeding patients with AHA . Cross‐reactivity is frequent in patients with anti‐human FVIII titers of >100 BU/mL.