Optimizing outcomes for patients with severe haemophilia A

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73864/1/j.1365-2516.2007.01552.x.pd

The history and evolution of the clinical effectiveness of haemophilia type a treatment: a systematic review.

First evidence of cases of haemophilia dates from ancient Egypt, but it was when Queen Victoria from England in the 19th century transmitted this illness to her descendants, when it became known as the "royal disease". Last decades of the 20th century account for major discoveries that improved the life expectancy and quality of life of these patients. The history and evolution of haemophilia healthcare counts ups and downs. The introduction of prophylactic schemes during the 1970s have proved to be more effective that the classic on-demand replacement of clotting factors, nevertheless many patients managed with frequent plasma transfusions or derived products became infected with the Human Immunodeficiency Virus (HIV) and Hepatitis C virus during the 1980s and 1990s. Recombinant factor VIII inception has decreased the risk of blood borne infections and restored back longer life expectancies. Main concerns for haemophilia healthcare are shifting from the pure clinical aspects to the economic considerations of long-term replacement therapy. Nowadays researchers' attention has been placed on the future costs and cost-effectiveness of costly long-term treatment. Equity considerations are relevant as well, and alternative options for less affluent countries are under the scope of further research. The aim of this review was to assess the evidence of different treatment options for haemophilia type A over the past four decades, focusing on the most important technological advances that have influenced the natural course of this "royal disease"

The relationship between target joints and direct resource use in severe haemophilia

Objectives Target joints are a common complication of severe haemophilia. While factor replacement therapy constitutes the majority of costs in haemophilia, the relationship between target joints and non drug-related direct costs (NDDCs) has not been studied. Methods Data on haemophilia patients without inhibitors was drawn from the ‘Cost of Haemophilia across Europe – a Socioeconomic Survey’ (CHESS) study, a cost assessment in severe haemophilia A and B across five European countries (France, Germany, Italy, Spain, and the United Kingdom) in which 139 haemophilia specialists provided demographic and clinical information for 1285 adult patients. NDDCs were calculated using publicly available cost data, including 12-month ambulatory and secondary care activity: haematologist and other specialist consultant consultations, medical tests and examinations, bleed-related hospital admissions, and payments to professional care providers. A generalized linear model was developed to investigate the relationship between NDDCs and target joints (areas of chronic synovitis), adjusted for patient covariates. Results Five hundred and thirteen patients (42% of the sample) had no diagnosed target joints; a total of 1376 target joints (range 1–10) were recorded in the remaining 714 patients. Mean adjusted NDDCs for persons with no target joints were EUR 3134 (standard error (SE) EUR 158); for persons with one or more target joints, mean adjusted NDDCs were EUR 3913 (SE EUR 157; average mean effect EUR 779; p < 0.001). Conclusions Our analysis suggests that the presence of one or more target joints has a significant impact on NDDCs for patients with severe haemophilia, ceteris paribus. Prevention and management of target joints should be an important consideration of managing haemophilia patients

Inhibitor clinical burden of disease: a comparative analysis of the CHESS data.

From Europe PMC via Jisc Publications Router.Publication status: PublishedBACKGROUND:Patients with hemophilia and inhibitors generally face greater disease burden compared to patients without inhibitors. While raising awareness of relative burden may improve the standard of care for patients with inhibitors, comparative data are sparse. Analyzing data drawn from the Cost of Haemophilia across Europe - a Socioeconomic Survey (CHESS) study, the aim of this study was to compare the clinical burden of disease in patients with severe hemophilia with and without inhibitors. Hemophilia specialists (N = 139) across five European countries completed an online survey between January-April 2015, providing demographic, clinical and 12-month ambulatory/secondary care activity data for 1285 patients. Patients with hemophilia who currently presented with inhibitors and those who never had inhibitors were matched on baseline characteristics via propensity score matching. Outcomes were compared between the two cohorts using a paired t-test or Wilcoxon signed-rank or McNemar's test. RESULTS:The proportion of patients who currently presented with inhibitors was 4.5% (58/1285). Compared to PS-matched patients without inhibitors, patients with inhibitors experienced more than twice the mean annual number of bleeds (mean ± standard deviation, 8.29 ± 9.18 vs 3.72 ± 3.95; p < .0001) and joint bleeds (2.17 ± 1.90 vs 0.98 ± 1.15; p < .0001), and required more hemophilia-related (mean ± standard deviation, 1.79 ± 1.83 vs 0.64 ± 1.13) and bleed-related hospitalizations (1.86 ± 1.88 vs 0.81 ± 1.26), hemophilia-related consultations (9.30 ± 4.99 vs 6.77 ± 4.47), and outpatient visits (22.09 ± 17.77 vs 11.48 ± 16.00) (all, p < .001). More than one-half (53.5%) experienced moderate/severe pain necessitating medication compared to one-third (32.8%) of patients without inhibitors (p = .01). CONCLUSIONS:Patients with hemophilia and inhibitors exhibited greater clinical burden and higher resource utilization compared to their peers without inhibitors. Strategies for improving the standard of care may alleviate burden in this population

Optimizing factor prophylaxis for the haemophilia population: where do we stand?

The hallmark of severe haemophilia, defined as a circulating level of factor (F) VIII (haemophilia A cases) or FIX (haemophilia B cases) of < 1%, is recurrent bleeding into muscles and joints (haemarthroses) from an early age of life. The inevitable result of such bleeding is progressive joint damage, leading to disabling arthritis that is typically evident within the first 2 decades of life in people with haemophilia who have limited or no access to regular factor replacement therapy, or those in whom factor replacement therapy is ineffective because of the presence of high-titre inhibitors. For children with severe haemophilia and no evidence of inhibitors, the unwanted musculoskeletal complications of severe haemophilia can be effectively prevented by the early initiation of a programme of long-term factor prophylaxis. In order to achieve the best outcome (a perfect musculoskeletal status for age) the programme of prophylaxis should be started before the onset of joint damage (primary prophylaxis). The gold standard primary prophylaxis regimen (the Malmo protocol) was pioneered and tested in Sweden and involves the infusion of 20-40 IU of FVIII per kg body weight on alternate days (minimum three times per week) for haemophilia A cases, and 20-40 IU kg(-1) of FIX twice weekly for haemophilia B cases. This protocol is, however, demanding on peripheral veins and very expensive. Modifications of the parent protocol such as starting primary prophylaxis with once-weekly infusions via peripheral veins with rapid escalation to full-dose prophylaxis or dose escalation based on frequency of bleeding are increasingly implemented in haemophilia treatment centres in countries that can afford the high cost of such programmes. These modified programmes can be achieved in the majority of young children with severe haemophilia without the need for central venous access devices (e.g. Port-a-Caths) and with avoidance of device-associated complications such as infection and thrombosis. In at least one centre, experience with arteriovenous fistulae as a strategy to ensure reliable venous access is being accumulated. The issues of compliance (adherence) to recommended prophylaxis protocols and when, if ever, to stop a programme of primary prophylaxis once started are real and require ongoing prospective studies. Such studies should incorporate outcome measures such as health-related quality-of-life and economic analyses