Turoctocog Alfa in Tertiary Prophylaxis of Hemophilia A or Is It Always About Bleeding? Case Studies
This case report from our own practice concerns our experience with the treatment of hemophilia A with turoctocog alfa. The intention is, among other things, to compare different outcomes in our two patients regarding their self-assessment of bleeding without objective validation.
Introduction
The treatment of hemophilia A has seen significant advancements in recent years, and we are pleased that this progress has reached our country as well. The life expectancy of patients with hemophilia A (HA) is now fortunately comparable to the general population, and the lives of these patients are becoming increasingly active, thanks to the improved condition of their joint apparatus. In our center, all patients with severe HA are on regular tertiary prophylaxis with factor VIII (FVIII) concentrate. Instead of standard half-life (SHL) factors, we have improved the quality of life for patients by less frequent administration of products with an extended half-life (EHL), among which turoctocog alfa is included. It is a human FVIII manufactured using recombinant DNA technology in a cell line derived from Chinese hamster ovary cells.
Case Study 1
The first patient is a 44-year-old man with severe HA without inhibitors. He was on on-demand therapy from 1994 and on regular prophylaxis since 2017. Due to hemophilic arthropathy with a target joint (left knee), he has a sedentary job.
Prophylaxis was initiated with SHL at a dose of 2000 IU/3 times a week (at a body weight of 83 kg). Under this regimen, the trough level of FVIII after the longest interval of 72 hours was repeatedly in the range of 1.5–2%. The annual bleeding rate (ABR) was reported as 4 times a year: 3 times into the left knee joint, and once into the elbow.
Given the availability of EHL, he switched to turoctocog alfa at a dose of 3000 IU/2 times a week. A comparable dose to SHL was chosen. Under this therapy, the trough level of FVIII after the longest interval of 96 hours was 4.2%. During the next 12 months, there was no spontaneous bleeding. The patient is fully satisfied with the therapy and is preparing for the implantation of a total knee replacement in the left knee joint.
Case Study 2
The second patient is a 60-year-old man also with severe HA without inhibitors. He was on on-demand therapy from 1994 and on regular prophylaxis since 2017. He is on full disability pension due to hemophilic arthropathy of both knee and elbow joints and ankles. His target joint is also the left knee.
Prophylaxis was initiated with SHL products at a dose of 2000 IU/3 times a week (at a body weight of 93 kg), as he did not want a higher dose. Due to 10 bleeding episodes within 6 months, the product was replaced with another SHL, where with the same dosing, the peak concentration reached 64% and the trough level after the longest interval of 72 hours repeatedly ranged between 1.5 and 2%. However, the frequency of bleeding did not significantly decrease, so additional doses were repeatedly administered, ultimately leading to a decision to change the treatment.
Subsequently, prophylaxis with turoctocog alfa at a dose of 3000 IU/2 times a week was initiated. Under this therapy, the trough level of FVIII after the longest interval of 96 hours was 2.1%. Over the next 6 months, the patient reported 5 bleeding episodes, so the dosage was increased to 3000 and 6000 IU per week. Nevertheless, he was not satisfied with the therapeutic effect (4 bleeding episodes into the left elbow joint within 3 months, despite a trough level of 5.2%). The dose of turoctocog alfa was then increased to 6000 IU/2 times a week, with a peak concentration of FVIII reaching 73% and a trough level of 7%. Despite this, the patient reported the same frequency of bleeding, and an inhibitor was ruled out. Therefore, the dose of turoctocog alfa was reduced back to the original dosing of 3000 IU/2 times a week, and the frequency of bleeding remained the same.
Discussion
Why mention these two cases? What do they have in common and what are the significant differences?
Common factors include the form and severity of hemophilia A, absence of inhibitors, treatment with plasma and cryoprecipitate until 1990, and lastly, hemophilic arthropathy with a target left knee joint.
The differences lie in the frequency of reported bleeding episodes despite comparable laboratory values. The explanation, to me, lies in the different interpretation of clinical issues. In the second patient, the consumption of FVIII concentrate was consistently above average since the introduction of on-demand therapy. In the absence of objective evidence of bleeding, it is difficult to say whether bleeding is indeed occurring or if the symptoms are “only” pain from chronic synovitis. Indeed, the patient himself also reports an effect from NSAIDs.
Conclusion
From our experience with EHL prophylaxis in all our patients, we can conclude satisfaction, as patients particularly appreciate the lower frequency of concentrate administration.
Assoc. Prof. MUDr. Petr Dulíček, Ph.D.
IVth Department of Internal Hematology, Faculty of Medicine, Charles University and University Hospital Hradec Králové
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