Prophylaxis versus episodic treatment to prevent joint disease in boys with severe hemophilia

Cornell University, Итак, New York, United States
New England Journal of Medicine (Impact Factor: 54.42). 08/2007; 357(6):535-44. DOI: 10.1056/NEJMoa067659
Source: PubMed

ABSTRACT Effective ways to prevent arthropathy in severe hemophilia are unknown.
We randomly assigned young boys with severe hemophilia A to regular infusions of recombinant factor VIII (prophylaxis) or to an enhanced episodic infusion schedule of at least three doses totaling a minimum of 80 IU of factor VIII per kilogram of body weight at the time of a joint hemorrhage. The primary outcome was the incidence of bone or cartilage damage as detected in index joints (ankles, knees, and elbows) by radiography or magnetic resonance imaging (MRI).
Sixty-five boys younger than 30 months of age were randomly assigned to prophylaxis (32 boys) or enhanced episodic therapy (33 boys). When the boys reached 6 years of age, 93% of those in the prophylaxis group and 55% of those in the episodic-therapy group were considered to have normal index-joint structure on MRI (P=0.006). The relative risk of MRI-detected joint damage with episodic therapy as compared with prophylaxis was 6.1 (95% confidence interval, 1.5 to 24.4). The mean annual numbers of joint and total hemorrhages were higher at study exit in the episodic-therapy group than in the prophylaxis group (P<0.001 for both comparisons). High titers of inhibitors of factor VIII developed in two boys who received prophylaxis; three boys in the episodic-therapy group had a life-threatening hemorrhage. Hospitalizations and infections associated with central-catheter placement did not differ significantly between the two groups.
Prophylaxis with recombinant factor VIII can prevent joint damage and decrease the frequency of joint and other hemorrhages in young boys with severe hemophilia A. ( number, NCT00207597 [].).

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Available from: Leonard A Valentino, Sep 02, 2014
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    • "In particular , infusions could be injected either on-demand or on regular basis (prophylaxis). According to the scientific literature , prophylaxis is the first choice therapy, especially for children with severe haemophilia A [8]. "
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    ABSTRACT: Objectives. Haemophilia A is a congenital disorder of coagulation that mainly affects males and causes a considerable use of resources, especially when hemophilic patients are treated with prophylaxis. The aim of the present review was to discuss and appraise the methodological aspects and results of published economic evaluations of haemophilia A treatments in the last decade. Methods. The literature search, performed by consulting four engines, covered studies published between 2002 and 2014. Full economic evaluations published in English language were identified and included in the review. A quality assessment of the studies was also carried out based on Drummond's checklist. Results. After careful evaluations of the identified records, 5 studies were reviewed. Primary and secondary prophylaxis resulted cost-effective compared to on-demand therapy: the ICER of primary prophylaxis ranged from €40.236 to €59.315/QALY gained, while the ICER of secondary prophylaxis was €40.229/QALY gained. Furthermore, 60% were high quality and 40% were medium quality studies. Conclusions. The review underlines the cost-effectiveness of prophylaxis versus on-demand treatment and the different methodological approaches applied. Further economic evaluations are required with models that reflect the clinical reality and consumption of resources in each country.
    01/2015; 2015:1-9. DOI:10.1155/2015/596164
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    • "Prophylactic treatment of severe haemophilia patients has Correspondence been shown to provide better overall care than on-demand treatment (Manco-Johnson et al, 2007; Collins et al, 2010). The relatively short half-life of human FVIII in the bloodstream mandates a prophylactic regimen of 3 weekly infusions . "
    British Journal of Haematology 04/2012; 158(1):149-52. DOI:10.1111/j.1365-2141.2012.09115.x · 4.96 Impact Factor
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    • "Radionuclide or isotopic synovectomy involves instillation of a radioisotope intra-articularly to sclerose the neo-vessels in the synovium (Manco-Johnson et al, 2002; Rodriguez-Merchan et al, 2007). The greatest advantage of this procedure includes outpatient setting, non-requirement for aggressive physical therapy or factor replacement and relatively lower costs (Rodriguez-Merchan et al, 2007). "
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    ABSTRACT: Haemophilia is an inherited disorder of clotting factor deficiencies resulting in musculoskeletal bleeding, including haemarthroses, leading to orthopaedic complications. The pathogenesis of haemophilic joint arthropathy continues to be explored and there is evidence to suggest that iron, cytokines, and neo angiogenesis can initiate synovial and early cartilage damage resulting in molecular changes and the perpetuation of a chronic inflammatory state. This joint arthropathy has long term consequences for bone health resulting in chronic pain and quality of life issues in the individual with haemophilia. Haemarthroses can be prevented by the administration of clotting factor concentrates (prophylaxis). However, high costs and the need for venous access devices in younger children continue to complicate recommendations for universal prophylaxis. In patients who fail or refuse prophylaxis, procedures, such as synovectomy and arthroplasty, can provide relief from repeated haemarthroses. The optimal timing of these, however, is not well defined. Prevention of joint arthropathy needs to focus on prevention of haemarthroses through prophylaxis, identifying early joint disease through the optimal use of cost effective imaging modalities and the validation of serological markers of joint arthropathy. Screening for effects on bone health and optimal management of pain to improve quality of life are, likewise, important issues.
    British Journal of Haematology 11/2011; 156(1):13-23. DOI:10.1111/j.1365-2141.2011.08919.x · 4.96 Impact Factor
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