PB0177 - Detection of IgG4 anti-FVIII levels as complementary test to define the ITI outcome in patients with hemophilia A: results from the BrazIT Study

Sunday, July 10, 2022

6:30 PM – 7:30 PM

Location: Exhibition

Presentation Format: In-Person

Presenting Author(s)

Daniel G. Chaves, Msc, PhD

Researcher
Fundação Centro de Hematologia e Hemoterapia de Minas Gerais (Hemominas), Minas Gerais, Brazil
Belo Horizonte, Minas Gerais, Brazil

Co-Author(s)

BA

Brendon Ayala

Researcher
Faculdade de Medicina, Universidade Federal de Minas Gerais, Minas Gerais, Brazil
Belo Horizonte, Minas Gerais, Brazil
Ricardo M. Camelo, MD, MSc, MBA

Physician
Faculty of Pharmacy, Universidade Federal de Minas Gerais
Belo Horizonte, Minas Gerais, Brazil
LE

Leina Y. Etto

Researcher
Centro de Hematologia e Hemoterapia da Paraíba (Hemoíba), Paraíba, Brazil
João Pessoa, Paraiba, Brazil
Ad

Andrea G. de Oliveira

Researcher
Fundação Centro de Hematologia e Hemoterapia de Minas Gerais (Hemominas), Minas Gerais, Brazil
Belo Horizonte, Minas Gerais, Brazil
VF

Vivian K B Franco

Researcher
Centro de Hematologia e Hemoterapia de Santa Catarina (Hemosc), Santa Catarina, Brazil
Florianópolis, Santa Catarina, Brazil
MR

Maria do Rosário F. Roberti

Researcher
Centro de Hematologia e Hemoterapia de Goiás (Hemogo), Goiás, Brazil
Goiânia, Goias, Brazil
RR

Rosângela A. Ribeiro

Researcher
Centro de Hematologia e Hemoterapia do Ceará (Hemoce), Ceará, Brazil
Fortaleza, Ceara, Brazil
MC

Maria Aline F. Cerqueira

Researcher
Centro de Hematologia e Hemoterapia do Piauí (Hemopi), Piauí, Brazil
Teresina, Piaui, Brazil
FC

Fábia M R A Callado

Researcher
Fundação de Hematologia e Hemoterapia de Pernambuco (Hemope), Pernambuco, Brazil
Recife, Pernambuco, Brazil
TA

Tânia H. Anegawa

Researcher
Centro Regional de Hematologia e Hemoterapia de Londrina, Paraná, Brazil
Londrina, Parana, Brazil
MC

Mônica H. Cerqueira

Researcher
Instituto de Hematologia do Estado do Rio de Janeiro (Hemorio), Rio de Janeiro, Brazil
Rio de Janeiro, Rio de Janeiro, Brazil
SR

Suely M. Rezende

Researcher
Faculdade de Medicina, Universidade Federal de Minas Gerais, Minas Gerais, Brazil
Belo Horizonte, Minas Gerais, Brazil

Background: Immune tolerance induction (ITI) is the treatment of choice to eradicate inhibitors in patients with inherited hemophilia A (PwHA). In addition to the Bethesda test, ELISA is an important assay to detect anti-factor VIII (FVIII) antibodies.

Aims: This study aimed to detect plasma levels of anti-FVIII IgG4 and to evaluate the agreement of the ELISA by using two different classes of FVIII to coat the plates - plasma-derived (pd) and recombinant (r) FVIII in PwHA after ITI.

Methods: We included PwHA who completed ITI from nine hemophilia centers. ITI outcome was defined as total/partial success and failure, based on inhibitor levels and FVIII pharmacokinetics. Comparison of IgG4 anti-FVIII levels was performed using paired and unpaired t-test. ROC curve analysis was performed to calculate sensitivity/specificity of the assays. Kappa coefficient of agreement was used to compare the assays. The study was approved by Ethical Committees and all participants/guardians signed a consent form.

Results: A total of 79 PwHA who completed ITI were included. A total of 56 (70.9%) and 23 (29.1%) patients had complete/partial success and failure, respectively. The majority of PwHA (73.4%) used pdFVIII during ITI. Median OD of anti-FVIII ELISA for PwHA who failed ITI was 2.37 (IQR 2.17-2.54) with rFVIII and 2.32 (IQR 2.04-2.45) with pdFVIII (p=0.002). Median OD for PwHA who had complete/partial response to ITI was 0.11 (IQR 0.06-0.43) with rFVIII and 0.12 (IQR 0.04-0.40) with pdFVIII (p=0.254). Samples were considered positive for IgG4 anti-FVIII in assays with rFVIII and pdFVIII when the OD value was above 0.17 (sensitivity=76.9%/specificity=81.5%) and 0.25 (sensitivity=71.2%/specificity=77.8%), respectively. The Kappa coefficient of agreement of anti-FVIII IgG4 between the two reagents was 0.85 (95% CI 0.73-0.96).

Conclusion(s): Either pdFVIII or rFVIII are useful on ELISA to detect IgG4 anti-FVIII in complementary test to define the ITI outcome in PwHA.