Cumulative analysis of inhibitor formation in patients with haemophilia A treated with sucrose‐formulated recombinant factor VIII

Bajwa, N. S.; Enriquez, Monika Maas; Gorina, Eduard; Lemm, G.

doi:10.1111/j.1365-2516.2008.01938.x

Cited by 8 publications

(4 citation statements)

References 5 publications

(3 reference statements)

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“…The second inhibitor patient had mild haemophilia and has developed a transient inhibitor before enrolment that was not clinically relevant. Our findings corroborate the low inhibitor incidence with rFVIII‐FS in previous studies and show a comparable safety profile with a recent meta‐analysis of a third‐generation recombinant FVIII product . This study was a non‐interventional study, and the investigator was responsible for therapy and analyses conducted; inhibitor and other laboratory measurements were performed locally and not in a central laboratory.…”

Section: Discussionsupporting

confidence: 89%

Prospective evaluation of treatment regimens, efficacy and safety of a recombinant factor VIII concentrate in haemophilia A: the German EffeKt study

Klamroth

Miesbach

Staritz³

2016

Haemophilia

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Section: Discussionsupporting

confidence: 89%

Prospective evaluation of treatment regimens, efficacy and safety of a recombinant factor VIII concentrate in haemophilia A: the German EffeKt study

Klamroth

Miesbach

Staritz³

2016

Haemophilia

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“…1). Of those, 15 were excluded: four owing to a retrospective design [17–20]; three to aggregation of data pertaining to PUPs and PTPs [21–23]; one to both [24]; three to a lack of available data on prior ED [25–27]; two to absence of follow‐up after pharmacokinetic evaluation [28,29]; one to use of an unspecified rFVIII type [30]; and one to inclusion of only previously reported prospective follow‐up data in PTPs [31]. One of those studies was excluded on the basis of information supplied by the investigators upon request [23].…”

Section: Resultsmentioning

confidence: 99%

Can B‐domain deletion alter the immunogenicity of recombinant factor VIII? A meta‐analysis of prospective clinical studies

Aledort

Navickis²,

Wilkes³

2011

Journal of Thrombosis and Haemostasis

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Summary. Background: As a result of the infrequency of inhibitors in previously treated patients (PTPs) with hemophilia A and the small size of available clinical studies, the immunogenicity of factor (F)VIII products has been difficult to assess. Objectives: A meta-analysis of prospective clinical studies was conducted to test the hypothesis that de novo inhibitor incidence differs between PTPs receiving full-length recombinant FVIII (FL-rFVIII) and B-domain deleted recombinant FVIII (BDD-rFVIII). Methods: Prospective studies with data on inhibitors in PTPs receiving FL-rFVIII or BDD-rFVIII were sought using systematic methods including bibliographic database searches. Data were secured from published study reports and inquiries to investigators. Between-group differences in inhibitor incidence rates were evaluated using mixed effects Cox regression. Results: Twenty-nine studies with 3012 total PTPs were included. Patients were at risk of de novo inhibitor development for a median of 79 exposure days. A total of 35 de novo inhibitors were observed. The cumulative hazard for all de novo inhibitors was 1.25% with a 95% confidence interval (CI) of 0.63-1.88%. The corresponding rate for high-titer de novo inhibitors [> 5 Bethesda units (BU)] was 0.29% (CI, 0.01-0.57%). Exposure to BDD-rFVIII was associated with an increased risk of all de novo inhibitors (hazard ratio, 7.26; CI, 2.12-24.9; P = 0.0016) and of high-titer de novo inhibitors (hazard ratio, 10.8; CI, 2.17-53.7; P = 0.0037), compared with FL-rFVIII. Conclusions: This meta-analysis of prospective clinical studies suggests that recombinant FVIII products may differ in immunogenicity.

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“…8 Interestingly, a very low incidence of FVIII inhibitors has been recently reported by a cumulative analysis of phase 1-4 clinical trials, postmarketing studies, and investigator-sponsored studies with the use of the sucrose-formulated rFVIII Kogenate AF. 31 A total of 2071 patients were included in the analysis, showing a very low cumulative de novo inhibitor rate (8.2%) in both PUPs and patients with <20 exposure days.…”

Section: Clinical Studies On Rfviii Productsmentioning

confidence: 99%

Recombinant Factor VIII Concentrates

Franchini

Lippi²

2010

Semin Thromb Hemost

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The development and introduction of recombinant factor VIII (rFVIII) concentrates nearly 20 years ago represented a major advance in the treatment of hemophilia A patients. Currently, first-, second- and third-generation rFVIII products are commercially available. Whereas first-generation rFVIII concentrates are stabilized with human albumin, second-generation rFVIII products contain sucrose instead of albumin in the final formulation. Finally, third-generation rFVIII products are manufactured without additional human or animal plasma proteins. The use of rFVIII concentrates has greatly improved the safety of replacement therapy in hemophilia A and virtually abolished the risk of blood-borne pathogen transmission. The remaining and most challenging aspect of hemophilia A management has now become the development of FVIII inhibitors. In this article we review the current knowledge on the commercially available rFVIII concentrates, analyzing their main characteristics. Moreover, results of the literature on their clinical hemostatic efficacy and safety are summarized.

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Cumulative analysis of inhibitor formation in patients with haemophilia A treated with sucrose‐formulated recombinant factor VIII

Cited by 8 publications

References 5 publications

Prospective evaluation of treatment regimens, efficacy and safety of a recombinant factor VIII concentrate in haemophilia A: the German EffeKt study

Prospective evaluation of treatment regimens, efficacy and safety of a recombinant factor VIII concentrate in haemophilia A: the German EffeKt study

Can B‐domain deletion alter the immunogenicity of recombinant factor VIII? A meta‐analysis of prospective clinical studies

Recombinant Factor VIII Concentrates

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