Factor VIII inhibitor treatment with high doses of F VIII

Stenbjerg, S.; Ingerslev, Jørgen; Zachariae, E

doi:10.1016/0049-3848(84)90257-3

Cited by 23 publications

(8 citation statements)

References 3 publications

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“…The development of inhibitory antibodies to FVIII is one of the most serious complications of hemophilia A treatment, as high titers preclude effective therapy with infused FVIII. Early studies with plasma‐derived FVIII indicated the prevalence of such inhibitors to be between 6 and 15% of all hemophilia A patients [17–20], or 21% for severe hemophilia patients [21,22]. Initial results of studies of rFVIII in previously untreated patients (PUPs) showed an incidence of 24–29% and caused speculation that the ultrapure plasma‐derived or recombinant protein produced in non‐human mammalian cell culture resulted in an increased risk of inhibitor formation, and an earlier age of onset [8,23].…”

Section: Introductionmentioning

confidence: 99%

Human recombinant DNA-derived antihemophilic factor in the treatment of previously untreated patients with hemophilia A: final report on a hallmark clinical investigation

Lusher

Abildgaard

Arkin

et al. 2004

Journal of Thrombosis and Haemostasis

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Summary. Background: Development of recombinant factor VIII (rFVIII) replacement therapy represents a milestone in the treatment of hemophilia A. Objective: The objective of this long‐term, multicenter study was to assess the safety, efficacy and rate of inhibitor formation of rFVIII (Kogenate®) in the treatment of hemophilia A in a group of previously untreated patients (PUPs). Patients and methods: Between January 1989 and October 1997, 102 evaluable patients (mean age 3.9 years) were treated with rFVIII as sole therapy for prophylaxis against bleeding or for hemorrhage. Patients with mild hemophilia were treated for ≥2 years, while those with moderate or severe hemophilia were treated for ≥5 years or 100 exposure days. Results: All patients responded well to therapy, so that 82% of bleeding episodes required a single infusion for treatment. Only four mild drug‐related adverse events were recorded during the study for an overall rate of 0.03% (4/13 464 infusions). No viral seroconversions were observed. The inhibitor incidence in PUPs with severe hemophilia was 29% (19/65). Overall, inhibitory antibodies developed in 21 patients (20.6%). Inhibitor titers were low (<10 Bethesda Units) in nine of the 21 patients despite continued episodic treatment with rFVIII and transient in eight patients receiving episodic treatment (seven low titer, one high titer). Eight high‐titer inhibitor patients were treated with immune‐tolerance induction therapy; five had successful outcomes. Conclusions: The observed incidence of inhibitor formation is similar to studies of PUPs receiving plasma‐derived FVIII. These results demonstrate the safety and efficacy of rFVIII in long‐term treatment of hemophilia A.

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Section: Introductionmentioning

confidence: 99%

Human recombinant DNA-derived antihemophilic factor in the treatment of previously untreated patients with hemophilia A: final report on a hallmark clinical investigation

Lusher

Abildgaard

Arkin

et al. 2004

Journal of Thrombosis and Haemostasis

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“…However, this took many months or even years to occur. [19][20][21][22] Other regimens used, with the aim of inducing IT, include so-called moderate to lowdosage FVIII regimens: 50 U FVIII/kg body weight/day, 25 U FVIII/kg body weight given every other day, or even low-dose FVIII administration on demand. [23][24][25][26][27] However, the success rate seems to be lower with these regi-mens, and median duration of treatment seems to be longer than with intensive programs.…”

Section: Therapeutic Regimens To Induce Immune Tolerancementioning

confidence: 99%

Factor VIII Inhibitors in Patients with Hemophilia A: Epidemiology of Inhibitor Development and Induction of Immune Tolerance for Factor VIII

Kreuz¹,

Becker²,

Lenz³

et al. 1995

Semin Thromb Hemost

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Factor (F) VIII inhibitor development remains one of the most serious complications in the treatment of hemophilia A. Former and recent studies on inhibitor development revealed that patients with severe hemophilia A and positive inhibitor family history are at highest risk of developing an inhibitor. Comparison of recent inhibitor incidence studies on previously untreated patients indicate that the risk of inhibitor development under treatment with recombinant FVIII concentrates is comparable to the inhibitor incidence under FVIII substitution by plasma-derived concentrates. However, longer observation periods are necessary to draw final conclusions. Since inhibitor development may result in inefficacy of FVIII concentrates in the treatment of severe bleedings, the induction of immune tolerance (IT) is still of main concern. Various regimens to induce IT by application of FVIII concentrates have been conducted up to now. Success rate appears to be influenced by low to high responder status, number of exposure days before onset of treatment, and dosage of therapeutic regimen. Especially, discontinuation of IT therapy seems to be associated with failure of therapy. Taking into account available data on IT therapy, we recommend early onset of a high dosage regimen in high responder patients as soon as possible after inhibitor detection, as this is associated with higher success rate and shorter elimination time.

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“…Immunosuppressive drugs 4,16,50,[121][122][123][124] and induction of immune tolerance to FVIII 21,61,[125][126][127][128][129][130][131][132][133][134] have both been used to suppress FVIII inhibitors. Frequently, therapy is a combination of treatment options designed to modulate the inhibitory effect by removing existing antibody, nonselectively suppressing production of additional antibody and selectively inducing immune tolerance to FVIII.…”

Section: Suppression Of Factor VIII Inhibitorsmentioning

confidence: 99%