Cargando…

Prevalence and Incidence of Non-neutralizing Antibodies in Congenital Hemophilia A— A Systematic Review and Meta-Analysis

Objectives: In hemophilia A the presence of non-neutralizing antibodies (NNAs) against Factor VIII (FVIII) may predict the development of neutralizing antibodies (inhibitors) and accelerate the clearance of administrated FVIII concentrates. This systematic review aimed to assess: (1) the prevalence...

Descripción completa

Detalles Bibliográficos
Autores principales: Abdi, A., Bordbar, M. R., Hassan, S., Rosendaal, F. R., van der Bom, J. G., Voorberg, J., Fijnvandraat, K., Gouw, S. C.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7221178/
https://www.ncbi.nlm.nih.gov/pubmed/32457734
http://dx.doi.org/10.3389/fimmu.2020.00563
_version_ 1783533315875143680
author Abdi, A.
Bordbar, M. R.
Hassan, S.
Rosendaal, F. R.
van der Bom, J. G.
Voorberg, J.
Fijnvandraat, K.
Gouw, S. C.
author_facet Abdi, A.
Bordbar, M. R.
Hassan, S.
Rosendaal, F. R.
van der Bom, J. G.
Voorberg, J.
Fijnvandraat, K.
Gouw, S. C.
author_sort Abdi, A.
collection PubMed
description Objectives: In hemophilia A the presence of non-neutralizing antibodies (NNAs) against Factor VIII (FVIII) may predict the development of neutralizing antibodies (inhibitors) and accelerate the clearance of administrated FVIII concentrates. This systematic review aimed to assess: (1) the prevalence and incidence of NNAs in patients with congenital hemophilia without inhibitors and (2) the association between NNAs and patient and treatment characteristics. Methods: We conducted a search in MEDLINE, Embase, Web of Science and the Cochrane database. We included cross-sectional and longitudinal studies reporting on NNAs in patients with hemophilia A and B, who were inhibitor-negative at the start of the observation period. Data were extracted on: hemophilia type and severity, patient and treatment characteristics, NNA prevalence and incidence, NNA assays and inhibitor development. Two independent reviewers performed study selection, data extraction and risk of bias assessment, using adapted criteria of the Joanna Briggs Institute. Studies were classified as high-quality when ≥5/9 criteria were met. NNA assays were classified as high-quality when both quality criteria were met: (1) use of positive controls and (2) competition with FVIII to establish FVIII-specificity. We reported NNA prevalence and incidence for each study. The pooled NNA prevalence was assessed for well-designed studies in previously treated patients, employing high-quality NNA assays. Results: We included data from 2,723 inhibitor-negative patients with hemophilia A, derived from 28 studies. Most studies were cross-sectional (19/28) and none reported on NNAs in hemophilia B. Study design was of high quality in 16/28 studies and the NNA assay quality was high in 9/28 studies. Various NNA assays were used, predominantly ELISA (18/28) with different cut-off values. We found a large variety in NNA prevalence (Range, 0–100%). The pooled NNA prevalence in high-quality studies was 25% (95% CI, 16–38%). The incidence of new NNA development was reported in one study (0.01 NNA per person-exposure day). Conclusion: This systematic review identified studies that were heterogeneous in study design, patient population and NNA assay type, with NNA prevalence ranging from 0 to 100% in inhibitor-negative patients with hemophilia A. The pooled NNA prevalence was 25% in high-quality studies including only previously treated patients and performing high-quality NNA assays.
format Online
Article
Text
id pubmed-7221178
institution National Center for Biotechnology Information
language English
publishDate 2020
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-72211782020-05-25 Prevalence and Incidence of Non-neutralizing Antibodies in Congenital Hemophilia A— A Systematic Review and Meta-Analysis Abdi, A. Bordbar, M. R. Hassan, S. Rosendaal, F. R. van der Bom, J. G. Voorberg, J. Fijnvandraat, K. Gouw, S. C. Front Immunol Immunology Objectives: In hemophilia A the presence of non-neutralizing antibodies (NNAs) against Factor VIII (FVIII) may predict the development of neutralizing antibodies (inhibitors) and accelerate the clearance of administrated FVIII concentrates. This systematic review aimed to assess: (1) the prevalence and incidence of NNAs in patients with congenital hemophilia without inhibitors and (2) the association between NNAs and patient and treatment characteristics. Methods: We conducted a search in MEDLINE, Embase, Web of Science and the Cochrane database. We included cross-sectional and longitudinal studies reporting on NNAs in patients with hemophilia A and B, who were inhibitor-negative at the start of the observation period. Data were extracted on: hemophilia type and severity, patient and treatment characteristics, NNA prevalence and incidence, NNA assays and inhibitor development. Two independent reviewers performed study selection, data extraction and risk of bias assessment, using adapted criteria of the Joanna Briggs Institute. Studies were classified as high-quality when ≥5/9 criteria were met. NNA assays were classified as high-quality when both quality criteria were met: (1) use of positive controls and (2) competition with FVIII to establish FVIII-specificity. We reported NNA prevalence and incidence for each study. The pooled NNA prevalence was assessed for well-designed studies in previously treated patients, employing high-quality NNA assays. Results: We included data from 2,723 inhibitor-negative patients with hemophilia A, derived from 28 studies. Most studies were cross-sectional (19/28) and none reported on NNAs in hemophilia B. Study design was of high quality in 16/28 studies and the NNA assay quality was high in 9/28 studies. Various NNA assays were used, predominantly ELISA (18/28) with different cut-off values. We found a large variety in NNA prevalence (Range, 0–100%). The pooled NNA prevalence in high-quality studies was 25% (95% CI, 16–38%). The incidence of new NNA development was reported in one study (0.01 NNA per person-exposure day). Conclusion: This systematic review identified studies that were heterogeneous in study design, patient population and NNA assay type, with NNA prevalence ranging from 0 to 100% in inhibitor-negative patients with hemophilia A. The pooled NNA prevalence was 25% in high-quality studies including only previously treated patients and performing high-quality NNA assays. Frontiers Media S.A. 2020-05-07 /pmc/articles/PMC7221178/ /pubmed/32457734 http://dx.doi.org/10.3389/fimmu.2020.00563 Text en Copyright © 2020 Abdi, Bordbar, Hassan, Rosendaal, van der Bom, Voorberg, Fijnvandraat and Gouw. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Abdi, A.
Bordbar, M. R.
Hassan, S.
Rosendaal, F. R.
van der Bom, J. G.
Voorberg, J.
Fijnvandraat, K.
Gouw, S. C.
Prevalence and Incidence of Non-neutralizing Antibodies in Congenital Hemophilia A— A Systematic Review and Meta-Analysis
title Prevalence and Incidence of Non-neutralizing Antibodies in Congenital Hemophilia A— A Systematic Review and Meta-Analysis
title_full Prevalence and Incidence of Non-neutralizing Antibodies in Congenital Hemophilia A— A Systematic Review and Meta-Analysis
title_fullStr Prevalence and Incidence of Non-neutralizing Antibodies in Congenital Hemophilia A— A Systematic Review and Meta-Analysis
title_full_unstemmed Prevalence and Incidence of Non-neutralizing Antibodies in Congenital Hemophilia A— A Systematic Review and Meta-Analysis
title_short Prevalence and Incidence of Non-neutralizing Antibodies in Congenital Hemophilia A— A Systematic Review and Meta-Analysis
title_sort prevalence and incidence of non-neutralizing antibodies in congenital hemophilia a— a systematic review and meta-analysis
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7221178/
https://www.ncbi.nlm.nih.gov/pubmed/32457734
http://dx.doi.org/10.3389/fimmu.2020.00563
work_keys_str_mv AT abdia prevalenceandincidenceofnonneutralizingantibodiesincongenitalhemophiliaaasystematicreviewandmetaanalysis
AT bordbarmr prevalenceandincidenceofnonneutralizingantibodiesincongenitalhemophiliaaasystematicreviewandmetaanalysis
AT hassans prevalenceandincidenceofnonneutralizingantibodiesincongenitalhemophiliaaasystematicreviewandmetaanalysis
AT rosendaalfr prevalenceandincidenceofnonneutralizingantibodiesincongenitalhemophiliaaasystematicreviewandmetaanalysis
AT vanderbomjg prevalenceandincidenceofnonneutralizingantibodiesincongenitalhemophiliaaasystematicreviewandmetaanalysis
AT voorbergj prevalenceandincidenceofnonneutralizingantibodiesincongenitalhemophiliaaasystematicreviewandmetaanalysis
AT fijnvandraatk prevalenceandincidenceofnonneutralizingantibodiesincongenitalhemophiliaaasystematicreviewandmetaanalysis
AT gouwsc prevalenceandincidenceofnonneutralizingantibodiesincongenitalhemophiliaaasystematicreviewandmetaanalysis