PB1146 - Determinants of successful immune tolerance induction in persons with hemophilia A – systematic review and meta-analysis

Tuesday, July 12, 2022

6:30 PM – 7:30 PM

Location: Exhibition

Presentation Format: In-Person

Presenting Author(s)

Ilja Oomen, MD

PhD student, MD
Amsterdam UMC location University of Amsterdam, Department of Pediatric Hematology, Meibergdreef 9, Amsterdam, The Netherlands
Amsterdam, Noord-Holland, Netherlands

Co-Author(s)

Ricardo M. Camelo, MD, MSc, MBA

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

Suely M. Rezende

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

Jan Voorberg

Professor, Principal investigator
Department of Molecular Hematology, Sanquin Research and Landsteiner Laboratory
Amsterdam, Noord-Holland, Netherlands
Maria Elisa Mancuso, MD, PhD

Senior Consultant in Haematology
IRCCS Humanitas Research Hospital
Milan, Lombardia, Italy
Johannes Oldenburg

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

Director, Haemophilia Clinic and Haemostasis Program
Hospital for Sick Children, Toronto, Canada
Toronto, Ontario, Canada
Davide Matino, MD

Assistant Professor
Department of Medicine, Division of Hematology, McMaster University, Hamilton, ON
Hamilton, Ontario, Canada
David Lillicrap, MD

Professor
Department of Pathology and Molecular Medicine, Queen's University
Kingston, Ontario, Canada
KF

Kathelijn Fischer, MD, PhD

Pediatric Hematologist
Center for Benign Haematology, Thrombosis and Haemostasis, Van Creveldkliniek, University Medical Center Utrecht, Utrecht University, The Netherlands
Utrecht, Utrecht, Netherlands
KF

Karin Fijnvandraat

Professor of Pediatric Hematology
Department of Pediatric Hematology, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands
Amsterdam, Noord-Holland, Netherlands
SG

Samantha C. Gouw, MD, PhD

Pediatric Hematologist
Amsterdam UMC, University of Amsterdam, Emma Children’s Hospital, Pediatric Hematology, Meibergdreef 9, Amsterdam, Netherlands; Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, The Netherlands.
Amsterdam, Noord-Holland, Netherlands

Background: Immune tolerance induction (ITI) is the only therapy to eradicate anti-factor VIII (FVIII) antibodies (inhibitors) in persons with hemophilia A (PwHA). However, this burdensome treatment fails in 10-40% of patients. In order to predict the ITI outcome is it important to identify predictors of ITI success.

Aims: To summarize the current evidence on factors associated with ITI outcome in PwHA.

Methods: On February 15 2021, a comprehensive literature search was conducted, which was updated on December 29 2021. Randomized controlled trials (RCT), cohort -, or case-control studies reporting on predictors for ITI outcome in PwHA were eligible for inclusion. ITI success was defined according to the methods of the investigators of the original studies. Data were extracted on study characteristics, outcome definitions, and predictors of ITI outcome, using a data collection form. Methodological quality was assessed by using an adapted Joanna Briggs Institute checklist for cohort studies. Studies were rated as high quality if ≥11/13 criteria were met.

Results: The literature searches yielded 1,079 unique papers of which 27 studies were included. We included 1 (4%) RCT and 26 (96%) cohort studies, involving a total of 1,734 PwHA. Six studies were rated as high quality (22%). ITI success was predominantly defined as negative inhibitor titer ( < 0.6 BU/mL), FVIII recovery ≥66% of expected, and FVIII half-life ≥6 hours (16/27; (59.3%)). Historical peak titer < 100 BU/mL, pre-ITI titer < 10 BU/mL, and peak titer during ITI < 100 BU/mL were associated with ITI success with pooled odds ratios of 1.50 (95% CI, 1.19-1.89), 1.68 (95% CI, 1.33-2.13), and 2.43 (95% CI, 1.58-3.74), respectively.

Conclusion(s): This systematic review and meta-analysis summarized and analyzed all available evidence of single variables that influence ITI outcome. However, the effects of multiple variables on ITI outcome were not investigated in this review.