Emicizumab Prophylaxis in Hemophilia A with Inhibitors

Oldenburg, Johannes; Mahlangu, Johnny; Kim, Benjamin; Schmitt, Christophe; Callaghan, Michael U.; Young, Guy; Santagostino, Elena; Kruse‐Jarres, Rebecca; Négrier, Claude; Kessler, Craig M.; Valente, Nancy; Asikanius, Elina; Lévy, Gallia; Windyga, Jerzy; Shima, Midori

doi:10.1056/nejmoa1703068

Cited by 845 publications

(1,447 citation statements)

References 16 publications

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“…In an ongoing phase 3 study in patients with inhibitors, thrombotic microangiopathy and thromboembolic events occurred after aPCC treatment, with doses averaging .100 U/kg per day for .1 day, during emicizumab prophylaxis. 28 However, no such events were observed in the current study. This may be because 22 of 23 aPCC administrations were at a lower dose than .100 U/kg per day for .1 day.…”

Section: Discussioncontrasting

confidence: 69%

Long-term safety and efficacy of emicizumab in a phase 1/2 study in patients with hemophilia A with or without inhibitors

et al. 2017

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Section: Discussioncontrasting

confidence: 69%

Long-term safety and efficacy of emicizumab in a phase 1/2 study in patients with hemophilia A with or without inhibitors

et al. 2017

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“…Given that the bispecific monoclonal antibody emicizumab has demonstrated significant reductions in bleeding in inhibitor patients [25], a question that has now been raised is: should ITI still be offered to patients who develop inhibitors? The current opinion amongst hemophilia treaters is that the majority would still opt for at least one round of ITI therapy.…”

mentioning

confidence: 99%

Inhibitors: A Need for Eradication?

Santagostino¹,

Ettingshausen²,

Jiménez‐Yuste³

et al. 2019

Acta Haematol

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The development of inhibitors against factor VIII (FVIII) concentrates represents a significant treatment complication for hemophilia. Immune tolerance induction (ITI) therapy eradicates inhibitors in 60–80% of patients, resulting in a normal FVIII response. This article, based on presentations at the 6th International Coagulation Meeting, held in Barcelona, Spain, in September 2017, provides an overview of management approaches for patients with inhibitors and briefly tabulates four cases of ITI therapy (first-line or rescue ITI therapy in pediatric and adult patients) with successful outcomes. Switching FVIII product from recombinant FVIII to plasma-derived FVIII/VWF concentrate may be helpful in eradicating inhibitors. The rate of decline of inhibitor titer in the initial stages of ITI therapy is a good indicator of the success or failure of therapy, although prognostic biomarkers are needed. The development of the bispecific monoclonal antibody emicizumab, which was recently shown to reduce bleeding in inhibitor patients, offers a potential alternative therapeutic option. However, the benefits of inhibitor eradication, including a wider choice of cheaper therapeutic products for preventing and treating bleeds, suggest that at least one attempt of ITI therapy should be offered to patients who develop inhibitors.

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“…The novel therapeutic compound emicizumab, a newly developed humanized bispecific monoclonal antibody to factors IXa and X for the treatment of inherited haemophilia with inhibitors, recently proved to be highly effective and received FDA approval in the USA [7, 8]. Due to the similarity of the disease mechanisms with alloantibodies to factor VIII in congenital haemophilia with inhibitors, and autoantibodies in AHA, similar effects of the compound in both disease entities must be expected [9, 10].…”

Section: Discussionmentioning

confidence: 99%

Emicizumab in the Treatment of Acquired Haemophilia: A Case Report

Möhnle

Pekrul

Spannagl

et al. 2019

Transfus Med Hemother

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The prognosis of acquired haemophilia A (AHA) is severe and treatment options are limited. Emicizumab is a novel bispecific humanized monoclonal antibody in the treatment of inherited AHA with inhibitors. An 83-year-old AHA patient with congestive heart failure and a high risk for thromboembolic and cardiac events who had initially been treated successfully with steroids and substitution of recombinant B-domain-deleted porcine FVIII developed severe bleeding complications and a secondary increase in inhibitor titres after 4 weeks of treatment. Conventional therapeutic strategies failed, and the patient was subsequently treated with emicizumab on off-label and named patient use premises. After the application of emicizumab, the clinical conditions stabilized and no further substitution of coagulation factors was needed. The patient could be discharged and survived 36 days in a cardiac rehabilitation centre without indications for spontaneous bleeding or thromboembolic events. We suggest that the effects of emicizumab in acquired haemophilia should be evaluated in clinical trials.

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Emicizumab Prophylaxis in Hemophilia A with Inhibitors

Abstract: Emicizumab prophylaxis was associated with a significantly lower rate of bleeding events than no prophylaxis among participants with hemophilia A with inhibitors. (Funded by F. Hoffmann-La Roche and Chugai Pharmaceutical; HAVEN 1 ClinicalTrials.gov number, NCT02622321 .).

Cited by 845 publications

References 16 publications

Long-term safety and efficacy of emicizumab in a phase 1/2 study in patients with hemophilia A with or without inhibitors

Long-term safety and efficacy of emicizumab in a phase 1/2 study in patients with hemophilia A with or without inhibitors

Inhibitors: A Need for Eradication?

Emicizumab in the Treatment of Acquired Haemophilia: A Case Report

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