UNASSIGNED: Hemophilia A is managed with coagulation clotting factor VIII (FVIII) therapy that poses significant challenges, such as a high treatment burden, immunogenicity, inconsistent hemostatic cover, poor treatment outcomes, and musculoskeletal progression despite adequate prophylactic treatment. Various non-factor therapies, such as several natural anticoagulant inhibitors and factor FVIII mimetics, have been developed to address these unmet needs. However, the role of emicizumab in addressing these unmet needs remains underexplored.
UNASSIGNED: This review delves into the evolution of hemophilia A replacement clotting therapy from plasma-derived products to recombinant products and, more recently, nonfactor therapies. It underscores the unmet needs of replacement therapy and explores the nonfactor therapies developed to address them. The review then comprehensively summarizes the clinical trial and real-world experience data, demonstrating how emicizumab tackles these unsatisfied demands.
UNASSIGNED: Replacement clotting factor therapies as the standard of care has exposed several needs that have yet to be addressed. However, data from numerous emicizumab clinical trials and real-world experience offer a promising outlook, suggesting that it may effectively address many unmet needs. As hemophilia treatment goals continue to evolve, the role of currently developed nonfactor therapies in hemophilia management is yet to be fully defined.

Acquired hemophilia A (AHA) is a rare autoimmune disorder due to autoantibodies against factor VIII, with a high mortality risk. It should be suspected in subjects with abnormal bleedings, especially subcutaneous bleed associated with prolonged activated partial thromboplastin time (aPTT). AHA is often idiopathic but is associated with autoimmune diseases, malignancies, pregnancy and postpartum period or drugs. Treatment is based on haemostatic agents as by-passants agents such as factor VIIa and activated prothrombine concentrate complex or recombinant porcine factor VIII for severe bleeding. Eradication of inhibitor should be established as soon as the diagnosis is confirmed with steroid alone often associated with cytotoxic agents or rituximab, depending on FVIII activity and inhibitor titer. The purpose of this review is to summarize the epidemiology, etiopathogenesis, diagnosis, treatment of AHA and discuss current recommendations.

Prophylactic replacement therapy for hemophilia A (hereditary factor VIII deficiency) is a success story of the production of coagulation factor concentrates from donor plasma. Recombinant factor concentrates, which are also produced with modified gene constructs for coagulation factor VIII in order to improve pharmacological properties, have since proven their worth. This successful development over many years of factor concentrates for the successful treatment of hemophilia patients has now been followed by the innovation of a factor VIII mimetic in the form of a monoclonal antibody, which was developed in Japan already some years back. Emicizumab is a humanized, bispecific monoclonal antibody for therapeutic use in hemophilia A. With this therapeutic agent, the treatment of the hereditary coagulation defect is based, for the first time, on a completely new active principle. The specific antibody simulates the properties of coagulation factor VIII as a cofactor for the formation of the tenase complex with the coagulation factors IX and X. As a result under steady state conditions almost normal thrombin and thus fibrin formation can be achieved.
UNASSIGNED: Die prophylaktische Substitutionsbehandlung bei Hämophilie A (hereditärer Faktor-VIII-Mangel) ist eine Erfolgsgeschichte der Herstellung von Gerinnungsfaktorenkonzentraten aus Spenderplasma. Inzwischen haben sich rekombinante Faktorenkonzentrate bewährt, die auch mit modifizierten Genkonstrukten für Gerinnungsfaktor VIII hergestellt werden, um die pharmakologischen Eigenschaften zu verbessern. An diese über viele Jahre erfolgreiche Entwicklung von Faktorenkonzentraten zur erfolgreichen Behandlung von Patienten mit Hämophilie hat sich nun die Neuigkeit eines Faktor-VIII-Mimetikums in Form eines monoklonalen Antikörpers angeschlossen, der bereits vor Jahren in Japan entwickelt wurde. Emicizumab ist ein humanisierter, bispezifischer monoklonaler Antikörper zur therapeutischen Anwendung bei Hämophilie A. Mit diesem Therapeutikum wird die Behandlung des hereditären Gerinnungsdefekts erstmals nach einem völlig neuen Wirkprinzip durchgeführt. Der spezifische Antikörper simuliert die Eigenschaften des Gerinnungsfaktors VIII als Kofaktor für die Bildung des Tenasekomplexes mit den Gerinnungsfaktoren IX und X. Damit kann unter Alltagsbedingungen eine ausreichende Thrombin- und Fibrinbildung erreicht werden.

UNASSIGNED: Hemophilia A (HA) is an X-linked hereditary bleeding disorder caused by deficiency of coagulation factor VIII activity. Emicizumab is a bispecific monoclonal antibody that replaces the function of activated FVIII and prevents bleeds in patients with hemophilia A. Emicizumab is expected to reduce the risk of severe bleeds in those patients with their subsequent complications. However, data about its safety and efficacy in patients with hemophilia A is limited. We aimed to evaluate safety and efficacy of Emicizumab prophylaxis in Egyptian pediatric patients with HA.
UNASSIGNED: A prospective cohort study was conducted on 88 HA patient who received prophylaxis with Emicizumab. Breakthrough bleeding episodes as well as annualized bleeding rate(ABR) were reported for all patients before and after Emicizumab prophylaxis. All adverse events during prophylaxis were reported to evaluate the safety of Emicizumab.
UNASSIGNED: Joint bleeds were present in 94 % of the patients. 58% of them had one target joint, 36.4% had more than one target joint while 5.6% had no target joints. 17% of patients were positive for FVIII inhibitors. The median annualized joint bleeding rate (AJBR) was reduced remarkably after Emicizumab prophylaxis (36 before versus zero after Emicizumab. Also, the median ABR was 48 before Emicizumab versus zero after Emicizumab. Eight patients developed mild breakthrough bleeding episodes. The most common adverse events were local reaction at the injection sites, headache, arthralgia, fever and diarrhea.
UNASSIGNED: Emicizumab prophylaxis was associated with significantly lower rate of bleeding events in patients with HA with and without inhibitors. The majority of patients had zero bleeds with Emicizumab prophylaxis.

Acquired hemophilia A (AHA) is a bleeding disorder caused by autoantibody (inhibitor) production targeting blood coagulation factor VIII (FVIII). It is characterized by sudden onset, and often causes extensive and severe bleeding in soft tissue. Acquired hemophilia A is diagnosed when coagulation tests show normal PT, prolonged APTT, decreased FVIII activity, normal VWF activity, and positive FVIII inhibitor. Hemostatic therapy mainly consists of bypass therapy, which activates the extrinsic coagulation pathway, bypassing the need for FVIII or factor IX. Emicizumab, a bispecific antibody that substitutes for FVIII function, can be used to prevent bleeding. Immunosuppressive therapy is necessary to suppress or eradicate inhibitors. The majority of patients go into remission with treatment, but some die from bleeding symptoms or infections associated with immunosuppressive therapy.

Acquired hemophilia A (AHA) is a rare autoimmune disease resulting from the development of autoantibodies directed against endogenous factor (F)VIII, leading to bleeding manifestations that can be life-threatening. The current standard hemostatic treatment involves the use of bypassing agents that circumvent FVIII (recombinant activated FVII, activated prothrombin complex concentrate, and recombinant porcine FVIII) that must be administered intravenously and possess a short half-life. These limitations and the risk of potentially fatal bleeding complications justify the early initiation of immunosuppressive treatment (IST) aimed at promptly eradicating the autoantibodies. IST is not without side effects, sometimes severe and possibly fatal, especially in persons with AHA who are generally older and have multiple comorbidities. Emicizumab, a bispecific antibody that mimics the action of FVIII, has emerged as an effective hemostatic therapy among persons with congenital hemophilia, whether complicated by the presence of anti-FVIII antibodies or not. Numerous arguments from recent clinical experiences suggest positioning emicizumab as a first-line treatment for AHA. This strategy has the potential to reduce bleeding complications and, importantly, the side effects associated with IST, which can be delayed and tailored to each patient.

UNASSIGNED: Emicizumab is a bispecific monoclonal antibody that mimics the function of factor VIII by binding to factor IXa and factor X to achieve haemostasis in haemophilia A. The long half-life and subcutaneous mode of administration makes emicizumab a compelling treatment option for bleeding prophylaxis. There is still limited real-world data on its use and management considerations, especially during surgical procedures. The objective of the study is to describe the real-world experience of emicizumab in a cohort of adult and paediatric haemophilia A patients in Singapore, including its use in the periprocedural setting.
UNASSIGNED: This was an observational study conducted at the 2 main haemophilia treatment centres in Singapore. All haemophilia A patients who commenced treatment with emicizumab before 1 July 2022 were recruited.
UNASSIGNED: A total of 18 patients with haemophilia A were included in this study. Ten (55.6%) patients had active inhibitors. The median annual bleeding rate for all patients before emicizumab use was 4.5 events (interquartile range [IQR] 2.8-8.3) compared with 0 events (IQR 0-0) after emicizumab was commenced (P=0). There were no adverse events of venous or arterial thrombosis, thrombotic microangiopathy, or death. A total of 6 procedures in 5 patients were performed during the study period with no major bleeding complications.
UNASSIGNED: Emicizumab effectively protects against bleeding in haemophilia A patients with and without inhibitors, including in children less than 12 years old. More studies are required to address clinical nuances, such as periprocedural management and the role of immune tolerance in patients with inhibitors on emicizumab.

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BACKGROUND: Reduced doses of emicizumab improve the affordability among patients in developing countries. However, the relationship between variant dose selection and efficacy in the real world of China is still unclear.
OBJECTIVE: This study aimed to investigate the efficacy and safety of emicizumab especially in those on reduced dose regimens in a real-world setting.
METHODS: We carried out a multicentre study from 28 hospitals between June 2019 and June 2023 in China and retrospectively analysed the characteristics including demographics, diagnosis, treatment, bleeding episodes, and surgical procedures.
RESULTS: In total, 127 patients with haemophilia A, including 42 with inhibitors, were followed for a median duration of 16.0 (IQR: 9.0-30.0) months. Median age at emicizumab initiation was 2.0 (IQR: 1.0-4.0) years. Median (IQR) consumption for loading and maintenance was 12.0 (8.0-12.0) and 4.2 (3.0-6.0) mg/kg/4 weeks, respectively. While on emicizumab, 67 (52.8%) patients had no bleeds, whereas 60 (47.2%) patients had any bleeds, including 26 with treated bleeds. Compared to previous treatments, patients on emicizumab had significantly decreased annualized bleeding rate, annualized joint bleeding rate, target joints and intracerebral haemorrhage. Different dosages had similar efficacy except the proportion of patients with treated spontaneous bleeds and target joints. Adverse events were reported in 12 (9.4%) patients. Postoperative excessive bleeding occurred following two of nine procedures.
CONCLUSIONS: This is the largest study describing patients with HA receiving emicizumab prophylaxis on variant dose regimens in China. We confirmed that nonstandard dose is efficacious and can be considered where full-dose emicizumab is ill affordable.

UNASSIGNED: With the treatment landscape continually evolving, it is vital that the hemophilia community have an overview of all published data for approved therapies, such as emicizumab, to support shared decision making.
UNASSIGNED: To bring together the clinical and real-world data for emicizumab use in people with congenital hemophilia A, regardless of age, disease severity, or factor VIII inhibitor status. Key focus areas were safety, efficacy, and quality of life (QoL).
UNASSIGNED: This scoping review used citation databases (PubMed, Embase, and the Cochrane Library) and manual searches of abstract books. Publications reporting original data for emicizumab in people with hemophilia A, published in English after December 2014, and reporting select endpoints were included. This narrative synthesis focused on zero bleeds, treated annualized bleeding rate (ABR), adverse events, and QoL measures.
UNASSIGNED: Overall, 97 publications were included (cut-off: August 9, 2022). Treated ABR remained low (calculated mean and median treated ABRs ranged between 0.7-1.3 and 0.0-1.4, respectively), and the median percentage of people with zero treated bleeds was 66.7%. The proportion of people experiencing treatment-related adverse events ranged from 0.0% to 60.0%; most were injection-site reactions. Across 37 publications reporting on safety and enrolling >2300 individuals, 11 thrombotic events and 4 thrombotic microangiopathies were reported. Data from well-established tools show QoL benefits with emicizumab.
UNASSIGNED: This scoping review consolidates the global published experience for emicizumab in people with hemophilia A and supports the fact that emicizumab has an acceptable safety profile, is effective and efficacious in bleed prevention, and is associated with improvements in QoL.