Failure of Combined Factor VIII and Cyclophosphamide to Suppress Antibody to Factor VIII in Hemophilia

Hruby, Marilyn A.; Schulman, Irving

doi:10.1182/blood.v42.6.919.919

Cited by 33 publications

(11 citation statements)

References 5 publications

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“…Various immunosuppressants, including cyclophosphamide, 6-mercaptopurine, corticosteroids, azathioprine, methotrexate, and chlorambucil have been utilized to suppress antibody titers or prevent the anamnestic response to factor VIII [5,10,16,30]. Conflicting reports as to the success of these agents are found in the literature [11]. Green treated two episodes of hemorrhage in a female nonnemophiliac in whom immunosuppressants failed on the first occasion, but were associated with a fall in the inhibitor level on the second [10].…”

Section: Immunosuppressive Therapymentioning

confidence: 99%

Management of Patients With Factor VIII or IX Inhibitors

Penner¹,

Kelly²

2008

Semin Thromb Hemost

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Section: Immunosuppressive Therapymentioning

confidence: 99%

Management of Patients With Factor VIII or IX Inhibitors

Penner¹,

Kelly²

2008

Semin Thromb Hemost

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“…Accordingly, the Malmö protocol is recommended only in patients resistant to ITI or at very high risk to fail (grade C recommendation based on level IV evidence). Immunosuppressive agents alone and/or high doses of intravenous immunoglobulins are not indicated [52][53][54][55][56] (grade B recommendation based on level III evidence).…”

Section: Classification Schemesmentioning

confidence: 99%

Italian guidelines for the diagnosis and treatment of patients with haemophilia and inhibitors

Gringeri

Mannucci

2005

Haemophilia

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The Italian Association of Haemophilia Centres reviewed and finally approved in November 2004 the new Italian Guidelines for the diagnosis and treatment of patients with clotting factor inhibitors. The recommendations have been based on the identification of levels of clinical evidence derived from the systematic review carried out in 2003 by the School of Health and Related Research, the University of Sheffield, UK, and further integrated by clinical studies published from 2003 to 2004. The Italian guidelines consist of six major domains concerning inhibitor definition, epidemiology, risk factors, diagnosis, inhibitor eradication, management of bleeding episodes, in patients with congenital and acquired coagulation disorders, with 121 statements, 59 synthesis and 54 recommendations. We report here recommendations and open issues concerning the diagnosis and monitoring of inhibitors, inhibitor eradication and the management of bleeding in patients with haemophilia A and B.

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“…Inhibitor eradication strategies using immunomodulatory agents have been tried since the 1970s. 66,67 Nowadays, immunomodulatory agents are mostly used as second-line therapy in patients who have already failed ITI. 68 The agents are generally administered as adjunctive therapy in combination with ITI.…”

Section: Eradication Of Antidrug Antibodies: What Is Already Known Inmentioning

confidence: 99%

Preventing or Eradicating Factor VIII Antibody Formation in Patients with Hemophilia A: What Can We Learn from Other Disorders?

Hassan

Fijnvandraat

Bom

et al. 2018

Semin Thromb Hemost

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Eradication of factor VIII (FVIII) specific neutralizing antibodies (also known as inhibitors) by the traditional method of immune tolerance induction (ITI) is costly and unsuccessful in one out of three patients. Furthermore, effective inhibitor prevention strategies are presently lacking. An overview is given in this narrative review of antidrug antibody prevention or eradication strategies that have been used in disorders beyond hemophilia A, with the aim of analyzing what we can learn from these strategies for hemophilia A. Prevention of antidrug antibody formation using rituximab, methotrexate, and intravenous immunoglobulins in patients with Pompe's disease seems effective but carries a high risk of adverse events. Based on studies in patients with rheumatoid arthritis and inflammatory bowel disease, it seems likely that treatment with methotrexate alone would also be able to prevent inhibitor formation in hemophilia A patients. Besides side effects, it is unclear whether immune tolerance to FVIII would persist after cessation of immunomodulatory therapy with methotrexate. A combination of cyclophosphamide and corticosteroids, used to treat antibody-mediated pure red cell aplasia, could be further investigated to eradicate inhibitors in hemophilia A patients who are refractory to ITI. In summary, insights gained from research on antidrug antibody formation in other diseases could be helpful in devising alternative treatment strategies for inhibitor development.

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Failure of Combined Factor VIII and Cyclophosphamide to Suppress Antibody to Factor VIII in Hemophilia

Cited by 33 publications

References 5 publications

Management of Patients With Factor VIII or IX Inhibitors

Management of Patients With Factor VIII or IX Inhibitors

Italian guidelines for the diagnosis and treatment of patients with haemophilia and inhibitors

Preventing or Eradicating Factor VIII Antibody Formation in Patients with Hemophilia A: What Can We Learn from Other Disorders?

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