Abstract
Life expectancy for people with hemophilia has improved and is now approaching that of the general population. This growing population will likely experience age-related co-morbidities such as cardiovascular diseases, diabetes, and chronic kidney disease.
Distribution of endogenous and exogenous (plasma or recombinant) factor IX between the intravascular and extravascular spaces have not been fully elucidated. In vivo recovery and elimination half-life have been suggested to be inadequate descriptors of effective pharmacokinetics (PK) of FIX, but that differences in distribution might be clinically important (Bjorkman Haemophilia 2013).
Pharmacokinetics (PK) of the long acting recombinant Factor IX albumin fusion protein (rIX-FP) with albumin demonstrated improved PK in a pivotal trial. However, no data exists in patients with end stage renal failure requiring dialysis. We present PK data for a single patient on dialysis who has received a single dose of rIX-FP,
Case: 71 y/o male with moderate hemophilia B with factor IX activity levels ranging between 2-4%. He averaged 2 bleeds per year until 2013, when his creatinine increased to 1.93-2.3 (GFR approx. 30mL/min). He averaged 2-4 joint or soft tissue bleeds since 2013. His GFR dropped to 7-10 mL/min in 2015. He tested negative for HCV, HIV, and multiple myeloma. A kidney biopsy and angiogram was not performed. He had nephrotic range proteinuria. His renal ultrasound was unremarkable. Hypertensive nephrosclerosis was the working diagnosis. The patient had a central line placed and AV fistula created in April 2016, which was complicated by bleeding despite factor replacement with Benefix (Pfizer). He began hemodialysis in May 2016 using a tunneled central catheter while awaiting maturation. The patient wanted to switch to peritoneal dialysis (PD). For the PD catheter placement we recommended Idelvion for factor replacement and conducted a pharmacokinetic study. A dose of 100 IU/kg (10,879 units) was administered. Factor IX levels were drawn at 1 hour (h), 24 (h), 72 (h), 168 (h), 216 (h), and 336 (h), with factor IX activity levels of 91%, 59%, 34%, 18%, 16%, and 11% respectively. Dialysis occurred 2 (h), 4 days, 1 week, and 11 days during the 2 week PK study. Samples were analyzed with a one stage assay using a silica activator (PTT A Diagnostica Stago) on a Stago Evolution
Conclusion: rIX-FP's demonstrated improved pharmacokinetic parameters in half-life, clearance and AUC in a recent study. To our knowledge, no data exist in patients with end-stage renal disease. We have presented data in a dialysis patient and show comparable PK parameters to that shown in the aforementioned study. Our patient's half-life (t1/2) was 165.2 (h) and AUC was 7663.5. It appears that dialysis and end-stage renal disease does not alter PK of rIX-FP. Further studies are needed in more hemophilia B patients with end-stage renal disease to confirm our findings.
Disclosures
Jain: Biogen: Speakers Bureau; Bayer: Membership on an entity's Board of Directors or advisory committees; Novo Nordisk: Honoraria.
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