EUHASS: The European Haemophilia Safety Surveillance system

Makris, Mike; Calizzani, Gabriele; Fischer, Kathelijn; Gilman, E A; Hay, C. R. M.; Lassila, Riitta; Lambert, Thierry; Ludlam, C. A.; Mannucci, Pier Mannuccio

doi:10.1016/s0049-3848(10)70150-x

Cited by 81 publications

(82 citation statements)

References 4 publications

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“…23,67 These steps can be accomplished in a retrospective fashion with large-sized rigorous nested-case control studies embedded in prospective registries, or with large perspective controlled observations. The European Hemophilia Surveillance Scheme (EUHASS) project 72 is an example of the latter. The National Institutes of Health inhibitor study 73 is an example of the former.…”

Section: Discussionmentioning

confidence: 99%

Clotting factor concentrate switching and inhibitor development in hemophilia A

Iorio

Puccetti

Makris

2012

Blood

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The development of alloantibodies or inhibitors is the most serious complication a patient with severe hemophilia can experience from treatment with clotting factor concentrates. Although common in previously untreated patients, inhibitor development is rare in multiply exposed, welltolerized patients. There has been a nonevidence-based reluctance to change concentrate because of a perceived greater inhibitor risk after the switch, even though most patients are now likely to be using a concentrate on which they did not begin. Inhibitors in previously treated patients are observed in approximately 2 per 1000 patient/years, which makes it difficult to study and compare rates among different products. Because the baseline inhibitor risk in previously treated patients may vary over time, it is important to compare the risk in patients switching to a new product with that in a parallel control group of nonswitching patients or within a case-controlled study.

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Section: Discussionmentioning

confidence: 99%

Clotting factor concentrate switching and inhibitor development in hemophilia A

Iorio

Puccetti

Makris

2012

Blood

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“…The European Hemophilia Safety Surveillance System (EUHASS) was established concurrently. 45 Adverse events and data for exposed populations are periodically reported, but a stable number of patients treated with a particular product over at least a 2-year period is required to estimate the cumulative incidence of inhibitors (at ED50 in PUPs) with that product. 46 This could limit the precision of product comparisons in this pharmacovigilance program.…”

Section: Possible Biological Explanations and Implicationsmentioning

confidence: 99%

Recombinant factor VIII products and inhibitor development in previously untreated boys with severe hemophilia A

Calvez

Chambost

Claeyssens-Donadel

et al. 2014

Blood

137

171

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Key Points• A currently marketed rFVIII product is associated with a higher risk of inhibitor development in boys with severe hemophilia A.• This result, validated by extensive sensitivity analyses, confirms a recently published study and cannot be explained by identified biases.Six recombinant factor VIII (rFVIII) products have been marketed worldwide. In 2013, the Research of Determinants of Inhibitor Development (RODIN) study group reported an unexpectedly high risk of inhibitor development with a second-generation full-length rFVIII (Product D) in previously untreated patients (PUPs) with severe hemophilia A (HA). In 1994, French public health authorities established a prospective cohort to monitor hemophilia treatment safety. A PUP subgroup was designed to investigate inhibitor risk factors. We analyzed this subcohort in view of the RODIN findings. After excluding 50 patients who participated in the RODIN study, the primary analysis focused on 303 boys with severe HA first treated with a rFVIII product. A clinically significant inhibitor was detected in 114 boys (37.6%). The inhibitor incidence was higher with Product D vs the most widely used rFVIII product (adjusted hazard ratio [aHR], 1.55; 95% confidence interval [CI], 0.97-2.49). Similar results were found for high-titer inhibitors and in 10 sensitivity analyses. No heterogeneity was observed between RODIN and our results. Combined aHRs were 1.58 (95% CI, 1.17-2.14) for all inhibitors and 1.70 (95% CI, 1.15-2.52) for high-titer inhibitors. Our results confirm the higher immunogenicity of Product D vs other rFVIII products in PUPs with severe HA. (Blood. 2014;124(23):3398-3408)

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“…At the end of every 12-month period, centres report the number of patients with each bleeding disorder under their care, as well as the number of patients treated with each clotting factor concentrate. EUHASS issues 3-monthly reports of the occurrence of adverse events during each quarter, as well as annual reports with more detailed analysis of events and persons at risk [31][32][33].…”

Section: European Haemophilia Safety Surveillancementioning

confidence: 99%

Safety surveillance in haemophilia and allied disorders

Lassila

Makris

2016

J Intern Med

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The introduction of clotting factor concentrates has transformed the lives of persons with inherited bleeding disorders. With the use of prophylactic treatment, it is now possible to prevent bleeding in these individuals. The early concentrates were contaminated with the HIV and hepatitis C viruses (HCV) and resulted in major morbidity and mortality in the recipients. Current products are much safer, especially in terms of infectious agents, but other adverse events such as alloantibodies (inhibitors), allergic reactions and thrombotic risks remain of concern. Approximately 30% of previously untreated patients with severe haemophilia A develop inhibitors, making this the most important issue in haemophilia care today. Recently, it was suggested that one of the most commonly used concentrates was associated with a higher inhibitor risk, but this was not supported by the evidence from all studies. Good safety surveillance systems are essential for all diseases and products but are particularly so in the group of individuals with inherited bleeding disorders treated with clotting factor concentrates who have suffered disproportionately from the adverse effects of their treatment. National and multinational systems are now in place to allow reporting of adverse events in patients with inherited bleeding disorders. All clinicians treating individuals with inherited bleeding disorders should prospectively report adverse events to treatment even if they are believed to be common and well recognized.

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EUHASS: The European Haemophilia Safety Surveillance system

Cited by 81 publications

References 4 publications

Clotting factor concentrate switching and inhibitor development in hemophilia A

Clotting factor concentrate switching and inhibitor development in hemophilia A

Recombinant factor VIII products and inhibitor development in previously untreated boys with severe hemophilia A

Safety surveillance in haemophilia and allied disorders

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