PB0008 - Neutralizing anti-emicizumab antibodies in a patient with Acquired Hemophilia A

Sunday, July 10, 2022

6:30 PM – 7:30 PM

Location: Exhibition

Presentation Format: In-Person

Presenting Author(s)

Behnaz Pezeshkpoor

Group Leader
University Clinic Bonn AöR, Institute of Experimental Haematology and Transfusion Medicine, Bonn, Germany
Bonn, Nordrhein-Westfalen, Germany

Co-Author(s)

NS

Nadja Sereda

Master Student
Institute of Experimental Hematology and Transfusion Medicine, University Hospital Bonn, Medical Faculty, University of Bonn, Germany
Bonn, Nordrhein-Westfalen, Germany
AB

Ann-Cristin Berkemeier

MD Student
University Clinic Bonn AöR, Institute of Experimental Haematology and Transfusion Medicine, Bonn, Germany
bonn, Nordrhein-Westfalen, Germany
JM

Jens Müller

Scientific Director
Institute of Experimental Haematology and Transfusion Medicine, University Hospital Bonn
Bonn, Nordrhein-Westfalen, Germany
SS

Sneha Singh

Postdoctoral researcher
Institute of Experimental Hematology and Transfusion Medicine, University Clinic Bonn
Bonn, Nordrhein-Westfalen, Germany
Samhitha Urs Ramaraje Urs, MSc

PhD Student
Institute of Experimental Haematology and Transfusion Medicine, University Clinic Bonn
Bonn, Nordrhein-Westfalen, Germany
CK

Claudia Klein

Physician
University Hospital Bonn; Institute of Experimental Haematologie and Transfusion Medicine
Bonn, Nordrhein-Westfalen, Germany
SH

Silvia Horneff

Senior physician
Institute of Experimental Hematology and Transfusion Medicine, University Hospital Bonn, Medical Faculty, University of Bonn, Germany
Bonn, Nordrhein-Westfalen, Germany
GG

Georg Goldmann

Senior physician
Institute of Experimental Hematology and Transfusion Medicine, University Hospital Bonn, Medical Faculty, University of Bonn, Germany
Bonn, Nordrhein-Westfalen, Germany
Natascha Marquardt, MD

Senior Physician
Institute for Experimental Hematology and Transfusion Medicine, University Clinic Bonn
Bonn, Nordrhein-Westfalen, Germany
Johannes Oldenburg

Professor, Chairman and Director
University Clinic Bonn AöR, Institute of Experimental Haematology and Transfusion Medicine, Bonn, Germany
Bonn, Nordrhein-Westfalen, Germany

Background: Emicizumab is a bispecific monoclonal antibody with a therapeutic FVIII-mimetic nature for prophylactic treatment of hemophilia A patients. Thus it seems to be an effective hemostatic therapy for Acquired Hemophilia A (AHA).

Aims: In the frame of this study, we diagnosed and characterized neutralizing anti-emicizumab antibodies associated with the loss of treatment efficacy in an AHA patient.

Methods: For detection and characterization of ADAs, an in-house multiplex microsphere-based immunoassay based on Luminex was established. The established immunoassay allows simultaneous screening for anti-FVIII and anti-emicizumab antibodies. Furthuremore, emicizumab F(ab)2 Fragment was produced to allow the identification of the ADAs against the FIX-F(ab) and FX-F(ab) arms of Emicizumab. The screening for ADAs was performed (IgG1-4 and IgA anti-human antibodies). The specificity of the ADAs was confirmed by competitive immunoassays with 100µg/ml Emicizumab.

Results: A 83 year old male AHA patient was treated with pdFVIII and 1,5mg/Kg emicizumab. In the beginning of his treatment he had expected levels of Emicizumab concentration in his plasma (~45µg/ml). 45 days after the start of the treatment a progressive decrease of the plasma concentration of emicizumab was observed. Five months later the plasma concentration of emicizumab dropped to < 10 µg/ml due to the supposed ADAs. Combined prednisolone and intravenous immunoglobulin treatment restored the plasma concentration of emicizumab. We were able to detect anti-emicizumab antibodies in the course of treatment of IgG isotype. The IgG subtype analysis revealed the presence of IgG1 and IgG2 antibodies. Competitive assays confirmed the respective specificity of the ADAs against emicizumab.

Conclusion(s): Although the incidence of neutralizing anti-emicizumab antibody is expected to be rare, with the increasing use of emicizumab in the therapy of AHA this number might rise. This study highlights the importance of a close monitoring and the need of laboratory assays to detect these antibodies.