PB0678 - Changing Recombinant Factor VIII for Plasma-derived FVIII during Immune Tolerance Induction: Results from the Brazilian Immune Tolerance (BrazIT) Study

Monday, July 11, 2022

6:30 PM – 7:30 PM

Location: Exhibition

Presentation Format: In-Person

Co-Author(s)

SR

Suely M. Rezende

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

Presenting Author(s)

Maíse M. Dias

Researcher
Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, São Paulo, Brazil
Ribeirão Preto, Sao Paulo, Brazil

Co-Author(s)

Ld

Laura Peixoto de Magalhães

Physician
Department of Clinics, Faculty of Medicine, Universidade Federal de Minas Gerais
Belo Horizonte, Minas Gerais, Brazil
Letícia Lemos Jardim, PhD

Researcher
Instituto René Rachou (Fiocruz Minas), Belo Horizonte, Minas Gerais, Brazil
Belo Horizonte, Minas Gerais, 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
RR

Rosângela A. Ribeiro

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

Fábia M R A Callado

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

Leina Y. Etto

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

Maria Aline F. Cerqueira

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

Claudia Santos Lorenzato

Haematologist
Centro de Hematologia e Hemoterapia do Paraná (HEMEPAR),
Curitiba, Parana, Brazil
IP

Ieda S. Pinto

Researcher
Fundação Centro de Hematologia e Hemoterapia do Pará (Hemopa), Pará, Brazil
Belém, Para, Brazil
�S

Édvis Santos Soares Serafim

Physician
Centro de Hematologia e Hemoterapia do Rio Grande do Norte (HEMONORTE)
Natal, Rio Grande do Norte, Brazil
AA

Andrea Aparecida Garcia

Researcher
Faculdade Regional de Medicina de São José do Rio Preto, Brazil
São José do Rio Preto,, Sao Paulo, Brazil
TA

Tânia H. Anegawa

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

Daniele Campos Fontes Neves

Researcher
Fundação Hemocentro de Rondônia (FHEMERON)
Porto Velho, Rondonia, Brazil
DT

Doralice Marvulle Tan

Physician
Department of Pediatric Onco-hematology, Faculdade de Medicina de Marília
Marília, Sao Paulo, Brazil
Ricardo M. Camelo, MD, MSc, MBA

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

Background: The main complication of factor VIII (FVIII) replacement in people with haemophilia A (PwHA) is the development of neutralising alloantibodies (inhibitors) against FVIII. Immune tolerance induction (ITI) is the only treatment for eradicating inhibitors.

Aims: We evaluated ITI outcome after changing the product from recombinant FVIII (rFVIII) to plasma-derived FVIII (pdFVIII) among PwHA who were not responding to rFVIII as a first-line therapy.

Methods: PwHA on ITI were enrolled at 15 haemophilia treatment centres. For this study, we included those who completed ITI, received only pdFVIII or changed from rFVIII to pdFVIII (n = 104). PwHA started ITI on a low-dose FVIII regimen (50 international units [IU]/kg 3x/week). Upon lack of response (no decline of inhibitor of at least 20% of peak levels 6 months after ITI start), high-dose FVIII regimen (100 IU/kg/day) and/or changing to pdFVIII for those who started ITI with rFVIII. Outcome was based on inhibitor titre and FVIII pharmacokinetics.

Results: A total of 8/104 patients (8%) changed from rFVIII into pdFVIII due to unresponsiveness to the former. Median age at inhibitor detection and ITI start were 4.6 years (interquartile range [IQR],2.0-12.8) and 13.2 years (IQR,5.1-25.5), respectively. While PwHA who received only pdFVIII had 68% of success, 100% of PwHA who changed from rFVIII to pdFVIII failed. Pre-ITI inhibitor peak, inhibitor titre immediately before ITI start, and peak during ITI were higher among PwHA who changed from rFVIII to pdFVIII in comparison with the ones who received exclusively pdFVIII during ITI.

Conclusion(s): In this study, all PwHA who received rFVIII as first-line product and changed to pdFVIII due to unresponsiveness to rFVIII, failed ITI. High inhibitor titres before and/or during ITI were higher among PwHA who changed from rFVIII to pdFVIII in comparison with the ones who received exclusively pdFVIII during ITI.