Pharmacokinetics, safety and efficacy of a recombinant factor IX product, trenonacog alfa in previously treated haemophilia B patients.

INTRODUCTION: Trenonacog alfa (IB1001) is a recombinant factor IX (rFIX) manufactured in Chinese hamster ovary (CHO) cells. IB1001 was evaluated in a multicentre clinical trial with haemophilia B patients. AIM: The aim was to establish IB1001 pharmacokinetic non-inferiority to comparator rFIX, safety and efficacy in previously treated patients (PTPs) with haemophilia B. METHODS: Subjects were severe or moderately severe haemophilia B adult and adolescent PTPs with no history of FIX inhibitors. RESULTS: IB1001 PK non-inferiority to comparator rFIX was demonstrated through ratio of AUC0-∞ in 32 subjects. IB1001 was well tolerated in all 76 treated subjects; the most common adverse drug reaction was headache (2.6% of subjects) and there were no reports of FIX inhibitors. Transient non-inhibitory binding FIX antibodies and anti-CHO cell protein antibodies developed in 21% and 29% of subjects respectively; no safety concerns were associated with development of these antibodies. Prophylaxis (mean duration ± SD: 17.9 ± 9.6 months, mean dose: 55.5 ± 12.9 IU/kg, median 1.0 infusion per week) was effective in preventing bleeds (median annual bleed rate: 1.52, interquartile range: 0.0-3.46). One or two IB1001 infusions resolved 84% of the bleeds, while for 84% of treatments haemostatic efficacy of IB1001 was rated excellent or good. IB1001 haemostatic efficacy for all 19 major surgeries was rated adequate or better than adequate. CONCLUSIONS: IB1001 is safe and efficacious for treatment of bleeds, routine prophylaxis and perioperative management in haemophilia B patients.

Safety and efficacy of plasma-derived coagulation factor IX concentrate (AlphaNine® SD) in patients with haemophilia B undergoing surgical intervention: a single institution retrospective analysis.

While coagulation factor replacement is essential in surgical intervention in haemophilia B patients, few studies are available on the safety and efficacy of plasma-derived factor IX (FIX) for haemostasis during surgery. This retrospective study examined outcomes in these patients. A total of 20 patients who underwent 29 surgical procedures at the Hemophilia Treatment Center at Orthopaedic Hospital in Los Angeles, California, were identified and their inpatient charts were reviewed and abstracted. Outcomes included pre- and postoperative FIX dosing, recovery of FIX, blood loss, use of blood products, safety and haemostatic response. Identified patients had mild (10%), moderate (15%) or severe (75%) haemophilia B, and average age at surgery was 48.5 years. All surgical procedures were major (orthopaedic 89.7%; abdominal 10.3%), all were completed under general anaesthesia, and average time in surgery was 3.25 h. Average hospital length of stay was 11.0 days [standard deviation (SD) = 8.5] and all patients were discharged home. All patients were treated with AlphaNine® SD at an average dose of 254.9 IU kg(-1) (SD = 65.4) on the day of surgery and the dose was adjusted over the course of hospital stay. Mean perioperative blood loss was 255.5 mL (SD = 283.1) and blood replacement was required in only two surgeries (6.9%). FIX recovery analysis performed preoperatively related well to FIX levels obtained. Identified patients had little blood loss perioperatively and had no bleeding related complications. Plasma-derived FIX pre- and postoperatively appeared to be a safe and effective treatment in haemophilia B patients undergoing surgery.

Same day outpatient transjugular liver biopsies in haemophilia.

Patients with haemophilia are at increased risk of hepatitis C infection because of prior transfusion of blood products. Virtually all haemophiliacs who received pooled blood products before the mid-1980s have been infected with hepatitis C. A liver biopsy is important to identify the extent of liver disease, and to help determine the necessity of interferon therapy. With factor replacement, in-hospital liver biopsy is safe. Thirty patients with haemophilia were evaluated for chronic hepatitis C infection. Eleven patients subsequently underwent successful transjugular liver biopsy in the outpatient setting after appropriate factor replacement. Mean +/- SD pre- and posthaemoglobin values were 15.8 +/- 0.79 and 14.4 +/- 0.71 g dL(-1) (P = ns). There was no significant change in heart rate, systolic or diastolic blood pressure during the monitoring period (P = ns) and no major complication was noted in perioperative follow-up. The mean length of the liver biopsy specimens was 1.7 +/- 0.3 cm, mean grade was 2 +/- 0.6 and mean stage was 2.3 +/- 1.2. Our experience demonstrates that outpatient transjugular liver biopsy can be safely performed in patients with haemophilia in the outpatient setting, avoiding the cost and need for hospital admission.