A plasma-derived factor VIII/von Willebrand factor product (Octanate) can eliminate inhibitors in patients with hemophilia A, according to research published in Haemophilia.
Octanate eradicated inhibitors in nearly 80% of patients studied, and patients who became inhibitor-free experienced an 86% reduction in monthly bleeding.
Adverse drug reactions occurred in about 42% of patients, and 4 of the 124 adverse events were considered serious.
Wolfhart Kreuz, MD, of HZRM (Haemophilia Centre Rhein Main) in Mörfelden-Walldorf, Germany, and his colleagues conducted this research as part of the ongoing ObsITI study. The trial enrolled 48 patients with hemophilia A and inhibitors.
Most patients–83.3% (n=40)—had 1 or more poor prognostic factors for immune tolerance induction (ITI) success. This includes age of 7 or older, having been diagnosed with inhibitors for 2 years or more, having an inhibitor titer of 10 BU or higher at the start of ITI, and prior ITI failure.
Patients received Octanate as the sole factor VIII product between December 2005 and October 2010. Patients who were “low responders” at the start of ITI (<5 BU) received 50–100 IU factor VIII kg-1 daily or every other day. And “high responders” (≥5 BU) received 100 IU factor VIII kg-1 every 12 hours.
During ITI, 4 patients received prophylaxis with bypassing agents—2 with activated prothrombin complex concentrates and 2 with recombinant factor VIIa.
The researchers assessed ITI efficacy according to 3 criteria. These were: (1) inhibitor titer <0.6 BU, (2) factor VIII recovery ≥80% of the predefined reference value of 1.5% IU-1 kg-1 body weight ≤1 hour post-injection, and (3) factor VIII half-life ≥7 hours.
The researchers defined “complete success” as meeting all 3 efficacy criteria, “partial success” as meeting 2 criteria, and “partial response” as meeting 1 criterion. If none of the criteria were met within the 36-month observation period, this was considered an ITI failure. Withdrawal from the study for administrative reasons was considered an ITI failure as well.
Treatment was deemed a complete success in 70.8% of patients (n=34) and a partial success in 6.3% (n=3). One patient (2.1%) had a partial response. Treatment failed in 20.8% of patients (n=10), all of whom had poor prognostic factors.
Overall, 79.2% of patients (38/48) became negative for inhibitors. These patients saw an 86% reduction in their monthly bleeding rate (P<0.0001), which decreased most dramatically during the initial 4 months of ITI. During that period, the mean monthly bleeding rate fell from 1.05 to 0.26.
The researchers noted that treatment outcome was significantly associated with a patient’s inhibitor titer level at the start of ITI (P=0.0068), the number of poor prognostic factors (P=0.0187), the monthly bleeding rate during ITI (P=0.0005), and peak inhibitor titer during ITI (P=0.0007).
There were 124 adverse drug reactions reported in 20 patients (41.7%). And there were 4 serious adverse drug reactions—intravenous catheter infection, febrile convulsion, gingivitis, and pyrexia. One reaction—allergic dermatitis—was considered possibly or probably related to treatment.
