Treatment of bleeding episodes in haemophilia A complicated by a factor VIII inhibitor in patients receiving Emicizumab. Interim guidance from UKHCDO Inhibitor Working Party and Executive Committee

Collins, Peter William; Liesner, Ri; Makris, Mike; Talks, Kate; Chowdary, Pratima; Chalmers, Elizabeth; Hall, Georgina; Riddell, Anne; Percy, Charles L.; Hay, C. R. M.; Hart, Daniel P.

doi:10.1111/hae.13495

Cited by 77 publications

(116 citation statements)

References 7 publications

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“…In a recent report, Collins et al made some recommendations for the treatment of bleeding episodes in haemophilia A complicated by a factor VIII inhibitor in patients receiving emicizumab . (1) Emicizumab should only be used in Comprehensive Care Hemophilia Centers.…”

Section: Resultsmentioning

confidence: 99%

Emicizumab: Review of the literature and critical appraisal

Rodríguez-Merchán¹,

Valentino

2018

Haemophilia

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Introduction Emicizumab‐kywh (ACE910) is a recombinant, humanized, asymmetric bispecific antibody that functions to bring activated FIX (FIXa) and zymogen FX into an appropriate steric conformation to medicate the activation of FX to FXa thereby mimicking the cofactor function of FVIIIa. Aim The objective of this manuscript was to review the development and potential role for emicizumab in the treatment of patients with haemophilia A with and without inhibitors. Methods A Cochrane Library and PubMed (MEDLINE) search focusing on emicizumab in haemophilia was conducted. Results In total, 37 citations were retrieved and serve as the database for the literature reviewed herein. Once‐weekly subcutaneous injection of emicizumab at three dose levels has been shown to be effective as prophylaxis to prevent bleeding in a majority haemophilia A patients with inhibitors to FVIII. Likewise, prevention of bleeding was also observed in more than two thirds of patients without inhibitors to FVIII. One antidrug antibody to emicizumab has been reported in over 600 treated patients, two have developed thromboembolic events and three thrombotic microangiopathy. These thrombotic complications have occurred in conjunction with FVIII‐bypassing agents, and none have been observed following recommendations from the manufacturer regarding concomitant use of bypassing agents. The median annual treated bleeding rates were decreased in patients with as well as those without an inhibitor to FVIII. Conclusion The principal advantage of emicizumab is subcutaneous administration and effectiveness irrespective of the presence of inhibitors. Emicizumab could conceivably represent a new epoch in the treatment of people with haemophilia A.

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Section: Resultsmentioning

confidence: 99%

Emicizumab: Review of the literature and critical appraisal

Rodríguez-Merchán¹,

Valentino

2018

Haemophilia

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“…Emicizumab has been recently approved by the US Food and Drug Administration and European Medicines Agency for routine prophylaxis in patients with haemophilia A and FVIII inhibitors who are not currently undergoing ITI and is proving to be an effective prophylactic therapy in these patients. Safety and efficacy in patients receiving ongoing ITI have not yet been established . Emicizumab has a mechanism of action that is not based on replacement or bypass therapy; it is a bispecific monoclonal antibody to activated FIX and factor X, which mimics the cofactor function of FVIII and can be administered subcutaneously .…”

Section: Prophylaxis In Patients With Inhibitorsmentioning

confidence: 99%

“…In light of these observations, recent guidance from the UK Haemophilia Centre Doctors’ Organisation (UKHCDO) recommends rFVIIa as a first‐line treatment for breakthrough bleeds in patients on emicizumab prophylaxis, with close observation for thrombosis. While pd‐aPCC can be used if there is no response to rFVIIa, or if other options (such as FVIII) are not available or appropriate, treatment should be administered in hospital with careful monitoring . In addition to the above fatality, a further four deaths have subsequently been reported in adults treated with emicizumab, one of whom was being treated in the US expanded access programme and three under compassionate use requests .…”

Section: Prophylaxis In Patients With Inhibitorsmentioning

confidence: 99%

“…Safety and efficacy in patients receiving ongoing ITI have not yet been established. 25 Emicizumab has a mechanism of action that is not based on replacement or bypass therapy; it is a bispecific monoclonal antibody to activated FIX and factor X, which mimics the cofactor function of FVIII and can be administered subcutaneously. 26,27 Phase III trial data showed that, in patients with haemophilia A and inhibitors, emicizumab prophylaxis was associated with a significant reduction in the annualised bleeding rate compared with no prophylaxis (P < 0.001).…”

Section: Emicizumabmentioning

confidence: 99%

“…28 In light of these observations, recent guidance from the UK ing. 25 In addition to the above fatality, a further four deaths have subsequently been reported in adults treated with emicizumab, one of whom was being treated in the US expanded access programme and three under compassionate use requests. 29 As with the death during the phase III trial, in all four of these instances, the treating physician considered that the cause was unrelated to emicizumab.…”

Section: Emicizumabmentioning

confidence: 99%

See 2 more Smart Citations

Inhibitors in haemophilia A and B: Management of bleeds, inhibitor eradication and strategies for difficult‐to‐treat patients

Ljung

Auerswald

Benson

et al. 2018

European J of Haematology

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The standard therapy for patients with haemophilia is prophylactic treatment with replacement factor VIII (FVIII) or factor IX (FIX). Patients who develop inhibitors against FVIII/FIX face an increased risk of bleeding, and the likelihood of early development of progressive arthropathy, alongside higher treatment‐related costs. Bypassing agents can be used to prevent and control bleeding, as well as the recently licensed prophylaxis, emicizumab, but their efficacy is less predictable than that of factor replacement therapy. Antibody eradication, by way of immune tolerance induction (ITI), is still the preferred management strategy for treating patients with inhibitors. This approach is successful in most patients, but some are difficult to tolerise and/or are unresponsive to ITI, and they represent the most complicated patients to treat. However, there are limited clinical data and guidelines available to help guide physicians in formulating the next treatment steps in these patients. This review summarises currently available treatment options for patients with inhibitors, focussing on ITI regimens and those ITI strategies that may be used in difficult‐to‐treat patients. Some alternative, non‐ITI approaches for inhibitor management, are also proposed.

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Non‐factor therapies for bleeding disorders: A primer for the general haematologist

Swan

Mahlangu²,

Thachil

2022

eJHaem

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Management of patients with severe bleeding disorders, particularly haemophilia A and B, and to a lesser extent, von Willebrand disease, has come on leaps and bounds over the past decade. Until recently, patients relied upon the administration of factor concentrates to prevent or treat bleeding episodes. Factor administration requires intravenous access and, in up to one-third of patients, leads to the development of neutralising antibodies, or inhibitors, which are associated with more frequent bleeding episodes and higher morbidity. Novel non-factor therapies may offer a solution to these unmet needs. In this review, we discuss the factor mimetics, particularly emicizumab, and the rebalancing agents, which inhibit antithrombin, tissue factor pathway inhibitor and activated protein C, and novel treatments to enhance von Willebrand factor levels. We review the available trial data, unanswered questions and challenges associated with these new treatment modalities. Finally, we provide practical management algorithms to aid the general haematologist when faced with a patient receiving emicizumab who requires surgery or may develop bleeding.

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Treatment of bleeding episodes in haemophilia A complicated by a factor VIII inhibitor in patients receiving Emicizumab. Interim guidance from UKHCDO Inhibitor Working Party and Executive Committee

Cited by 77 publications

References 7 publications

Emicizumab: Review of the literature and critical appraisal

Emicizumab: Review of the literature and critical appraisal

Inhibitors in haemophilia A and B: Management of bleeds, inhibitor eradication and strategies for difficult‐to‐treat patients

Non‐factor therapies for bleeding disorders: A primer for the general haematologist

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