Abstract Number: PB0486
Meeting: ISTH 2021 Congress
Background: Emicizumab is a humanized bispecific monoclonal antibody that bridges activated factor IX and factor X to mimic the function of factor VIII (FVIII). It suppresses the bleeding tendency in hemophilia A patients with or without FVIII inhibitors. At Sapporo Tokushukai Hospital, we experienced a case of an adult FVIII inhibitor-positive hemophilia A patient in whom treatment with emicizumab was discontinued owing to increased bleeding frequency and prolonged activated partial thromboplastin time. Because of these signs, we suspected decrease in the efficacy of emicizumab.
Aims: To analyze the mechanisms underlying the decrease in the efficacy of emicizumab, we analyzed the factors affecting the pharmacological effect of emicizumab in the plasma of the patient.
Methods: Residual plasma from blood samples that had been collected from the patient for clinical testing were used to measure the following items: concentration of emicizumab in the plasma, determined by enzyme-linked immunosorbent assay; anti-drug antibody (ADA) against emicizumab, detected by electrochemiluminescence (ECL); and neutralizing activity against emicizumab, measured by a modified Bethesda method using emicizumab-spiked FVIII-deficient plasma.
Results: Before emicizumab treatment was discontinued, emicizumab concentration in the plasma was 1.75 µg/mL after the first bleeding was observed, and ADA was detected. After discontinuation of emicizumab treatment, no emicizumab was detected in the plasma. The ECL signal derived from ADA increased transiently following discontinuation of emicizumab and then attenuated. Neutralizing activity against emicizumab was observed in the plasma after the discontinuation of emicizumab treatment.
Conclusions: The appearance of ADA decreased the concentration of emicizumab in the plasma, leading to a reduction in its efficacy. This indicates that the ADA had neutralizing activity against emicizumab.
To cite this abstract in AMA style:Kawasaki R, Kaneda M, Noguchi M, Matsumoto N, Abe H, Tashiro Y, Inokuchi Y, Yasuno H, Soeda T, Yoshimura Y, Oka T. Characteristics of Anti-drug Antibody against Emicizumab Analyzed Using Hemophilia A Patient-derived Plasma Samples [abstract]. Res Pract Thromb Haemost. 2021; 5 (Suppl 2). https://abstracts.isth.org/abstract/characteristics-of-anti-drug-antibody-against-emicizumab-analyzed-using-hemophilia-a-patient-derived-plasma-samples/. Accessed November 29, 2021.
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