1.
Outcomes for studies assessing the efficacy of hemostatic therapies in persons with congenital bleeding disorders
Aquino CC, Borg Debono V, Germini F, Pete D, Kempton CL, Young G, Sidonio R, Croteau SE, Dunn AL, Key NS, et al
Haemophilia : the official journal of the World Federation of Hemophilia. 2021
Abstract
INTRODUCTION Management strategies and hemostatic treatments to achieve control of bleeding are relevant across many disease areas. Identification of primary outcomes for studies assessing hemostatic intervention was the objective of a National Heart, Lung and Blood Institute (NHLBI) sponsored multidisciplinary initiative. The aim of this report is to summarize the evidence reviewed, and the outcomes identified by the subgroup tasked to assess outcomes for inherited bleeding disorders. METHODS The subgroup decided to focus on haemophilia, the prototypal congenital bleeding disorder and the one with the largest available body of evidence. MEDLINE, EMBASE and PsycINFO, The Cochrane Review, CINAHL, and Web of Science were searched for systematic and narrative reviews on outcomes used in haemophilia clinical trials. Three different clinical goals were identified as typical objectives of future research. RESULTS Out of 1322 unique citations, 24 reviews published in the period 2002-2019 were included. We identified 113 outcome measures, categorized in 6 domains: health-related quality of life (HRQoL), comorbidities and mortality, overall physical functioning and participation, bleeding and hemostasis, joint health, and costs and resource use. Three different clinical goals were identified as typical objectives of future research: Episodic 'on demand' replacement therapy, prevention of bleeding (Prophylaxis), and long-term and overall impact of bleeding. For each of these scenarios, specific outcomes were recommended. CONCLUSIONS Primary outcomes for clinical trials assessing the efficacy of hemostatic treatment in achieving control, prevention and limiting long-term consequences of bleeding in inherited bleeding disorders are suggested, and their strength and limitations discussed.
2.
Pharmacokinetic characteristics of factor VIII and IX concentrates – a systematic review
Xi M, Blanchette V, Blatny J, Collins P, Dunn A, Fischer K, Hermans C, Navarro-Ruan T, Kavakli K, Jackson S, et al
Journal of Thrombosis and Haemostasis. 2015;13((Suppl. 2)):357.. Abstract No. PO262-MON.
3.
Systematic review of the published evidence on the pharmacokinetic characteristics of factor VIII and IX concentrates
Xi M, Navarro-Ruan T, Mammen S, Blanchette VS, Hermans CR, Morfini M, Collins PW, Fischer K, Neufeld EJ, Young G, et al
Blood. 2014;124((21)): Abstract No. 2818
4.
Rate of inhibitor development in previously untreated hemophilia A patients treated with plasma-derived or recombinant factor VIII concentrates: a systematic review
Iorio A, Halimeh S, Holzhauer S, Goldenberg N, Marchesini E, Marcucci M, Young G, Bidlingmaier C, Brandao LR, Ettingshausen CE, et al
Journal of Thrombosis and Haemostasis. 2010;8((6):):1256-65.
Abstract
Background: Different rates of inhibitor development after either plasma-derived (pdFVIII) or recombinant (rFVIII) FVIII have been suggested. However, conflicting results are reported in the literature. Objectives: To systematically review the incidence rates of inhibitor development in previously untreated patients (PUPs) with hemophilia A treated with either pdFVIII or rFVIII and to explore the influence of both study and patient characteristics. Methods: Summary incidence rates (95% confidence interval) from all included studies for both pdFVIII and rFVIII results were recalculated and pooled. Sensitivity analysis was used to investigate the effect of study design, severity of disease and inhibitor characteristics. Meta-regression and analysis-of-variance were used to investigate the effect of covariates (testing frequency, follow-up duration and intensity of treatment). Results: Two thousand and ninety-four patients (1167 treated with pdFVIII, 927 with rFVIII; median age, 9.6 months) from 24 studies were investigated and 420 patients were observed to develop inhibitors. Pooled incidence rate was 14.3% (10.4-19.4) for pdFVIII and 27.4% (23.6-31.5) for rFVIII; high responding inhibitor incidence rate was 9.3% (6.2-13.7) for pdFVIII and 17.4% (14.2-21.2) for rFVIII. In the multi-way anova study design, study period, testing frequency and median follow-up explained most of the variability, while the source of concentrate lost statistical significance. It was not possible to analyse the effect of intensity of treatment or trigger events such as surgery, and to completely exclude multiple reports of the same patient or changes of concentrate. Conclusions: These findings underscore the need for randomized controlled trials to address whether or not the risk of inhibitor in PUPs with hemophilia A differs between rFVIII and pdFVIII. 2010 International Society on Thrombosis and Haemostasis.
5.
Rate of inhibitor development in hemophilia A patients treated with plasma derived or recombinant factor VIII concentrates. A systematic review of the literature
Iorio A, Halimeh S, Bidlingmaier C, Brandao LR, Escuriola-Ettingshausen C, Goldenberg NA, Gringeri A, Holzhauer S, Kenet G, Knoefler R, et al
Blood. 2009;114((22):): Abstract No. 3154.