PB0243 - Detection of an anti-drug antibody against emicizumab in clinical practice: experience from one center in France

Sunday, June 23, 2024

13:45 – 14:45 ICT

Room: Exhibition Hall

Presenting Author(s)

Claire Auditeau, PharmD

PharmD, PhD Student
Hémostase Inflammation Thrombose (HITh) UMR-S1176 INSERM Université Paris-Saclay Le Kremlin-Bicêtre France
Kremlin-Bicêtre, Ile-de-France, France

Co-Author(s)

CV

Carla Valsecchi

Researcher
Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
Milan, Lombardia, Italy
NB

Nûn Bentounes

Resident
Laboratoire d'Hématologie Biologique, AP-HP, Hôpital Necker Enfants Malades, Paris, France.
Paris, Ile-de-France, France
AH

Annie Harroche

Pediatric haematologist
Centre de Traitement de l'Hémophilie, AP-HP, Hôpital Necker Enfants Malades, Paris, France.
Paris, Ile-de-France, France
CB

Cécile Bally

Haematologist
Centre de Traitement de l'Hémophilie, AP-HP, Hôpital Necker Enfants Malades, Paris, France.
Paris, Ile-de-France, France
DL

Dominique Lasne

PharmD PhD
Laboratoire d'Hématologie Biologique, AP-HP, Hôpital Necker Enfants Malades, Paris, France.
Paris, Ile-de-France, France
Flora Peyvandi, MD, PhD

Full Professor
Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Università degli Studi di Milano, Department of Pathophysiology and Transplantation
Milan, Lombardia, Italy
Delphine Borgel

Professor
Hémostase Inflammation Thrombose (HITh) UMR-S1176 INSERM Université Paris-Saclay Le Kremlin-Bicêtre France
Paris, Ile-de-France, France

Background: Emicizumab is an antibody that mimics the function of factor VIII and has been approved for prophylaxis in hemophilia A patients. However, some rare patients developed a neutralizing antidrug antibody to emicizumab (ADA).

Aims: Screen patients with suspected ADA and then describe clinical and laboratory features of ADA-positive patients compared to ADA-negative patients.

Methods: We collected clinical and laboratory data on seven patients with a suspected ADA. They were bleeding and/or had prolonged APTT, prompting emicizumab concentration measurement, which was low or undetectable. An ADA screening was performed as described by Valsecchi et al. (JTH 2021). Total immunoglobulins were purified, and potential ADAs were detected by western blot using biotin-labeled emicizumab. A bridging modified ELISA was then performed, relying on ADAs' ability to bridge coated emicizumab and biotin-labeled emicizumab.

Results: The circulating concentration of emicizumab was undetectable ( < 1µg/mL) for 4 patients, at 1 µg/mL for 1 patient, and higher for 2 patients (13 and 15µg/mL). APTT was prolonged in patients with emicizumab concentration ≤1µg/mL (table). Six patients presented a bleeding event, either spontaneous (2/6) or traumatic (4/6). An ADA was detected by the Western Blot and the modified ELISA in the two patients (figure) with spontaneous bleeding. The initiation of emicizumab was more recent in ADA-positive than in ADA-negative patients (6.5 ± 0.6 and 34.5 ± 22.0 months respectively). In ADA-positive patients, emicizumab was stopped, and induced immune tolerance was begun because of an anti-factor VIII inhibitor. In ADA-negative patients, detectable concentrations of emicizumab were reached after correction for compliance or defective administration of emicizumab.

Conclusion(s): ADA-positive patients with persistent undetectable emicizumab concentration had spontaneous bleeding. We propose to check for the presence of ADA in case of patients with loss of response to emicizumab therapy and appearance of bleeding manifestations. ADA could be measured by methods described by Valsecchi et al.