Predictors of the outcome of immune tolerance induction in patients with haemophilia A and inhibitors: The Brazilian Immune Tolerance (BrazIT) Study protocol.
Journal
PloS one
ISSN: 1932-6203
Titre abrégé: PLoS One
Pays: United States
ID NLM: 101285081
Informations de publication
Date de publication:
2021
2021
Historique:
received:
26
04
2021
accepted:
03
08
2021
entrez:
26
8
2021
pubmed:
27
8
2021
medline:
15
12
2021
Statut:
epublish
Résumé
The development of inhibitors is the main complication of haemophilia A (HA) treatment. Immune tolerance induction (ITI) is the treatment of choice for inhibitor eradication. We describe the methodology of the Brazilian Immune Tolerance Induction (BrazIT) Study, aimed to identify clinical, genetic, and immune biomarkers associated with response to ITI and inhibitor recurrence. This cohort study includes people with HA (PwHA) and inhibitors (a) who require bypassing agents to treat and/or prevent bleeding, and (b) who are at any stage of ITI treatment. Patients are included in each haemophilia treatment centre (HTC). Factor VIII (FVIII) and inhibitor assessments are performed at local laboratories of each HTC. The ITI regimen followed the national protocol of the Brazilian Ministry of Health. All PwHA starts with low-dose ITI (50 IU/kg three times weekly); high-dose regimen (100 IU/kg daily) is used if there is lack of response to the low-dose ITI. Outcomes are classified as total or partial success, and failure. Standardized case report forms with clinical, laboratory, and treatment data are collected from medical files and interviews. Blood samples are collected for genetic and immune biomarkers at the time of inclusion in the study and at the end of ITI. The study is ongoing and, currently, 202/250 (80.8%) PwHA from 15 HTCs have been included. BrazIT Study is the largest cohort of PwHA and inhibitor under treatment with the same ITI regimen reported to date. This study is likely to contribute with novel predictors of ITI response.
Identifiants
pubmed: 34437573
doi: 10.1371/journal.pone.0256265
pii: PONE-D-21-13311
pmc: PMC8389515
doi:
Substances chimiques
Antibodies, Bispecific
0
Antibodies, Monoclonal, Humanized
0
Biomarkers
0
emicizumab
7NL2E3F6K3
Factor VIII
9001-27-8
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e0256265Commentaires et corrections
Type : CommentIn
Déclaration de conflit d'intérêts
RMC has received speaker/consultant fees and scientific event grants from Hoffman-La Roche and Takeda. DGC and LWZ have no conflicts of interest to declare. SMR works as an advisor to the Brazilian Program of Inherited Bleeding Disorders (Brazilian Ministry of Health) and received consultancy fees from the Brazilian Ministry of Health. This does not alter our adherence to all PLOS ONE policies on sharing data and materials. After the publication of the final analysis, the data can be shared upon request and guarantee of the confidentiality of each participant. Furthermore, this must adhere to the rules of the Brazilian ethical resolutions for the development of research with human beings.
Références
Int J Lab Hematol. 2015 May;37 Suppl 1:52-60
pubmed: 25976961
Br J Haematol. 2017 Sep;178(6):971-978
pubmed: 28836262
Haemophilia. 2020 Jan;26(1):41-46
pubmed: 31746522
Haemophilia. 2009 Jan;15(1):142-9
pubmed: 18976255
Eur J Haematol. 2018 Oct;101(4):435-456
pubmed: 29889317
Br J Haematol. 2021 Feb;192(3):621-625
pubmed: 33316077
Haematologica. 2019 Feb;104(2):236-244
pubmed: 30514798
Haemophilia. 2010 Jul;16 Suppl 5:17-21
pubmed: 20590851
Thromb Haemost. 2016 Aug 31;116 Suppl 1:S10-7
pubmed: 27528280
Haemophilia. 1996 Oct;2(4):224-8
pubmed: 27214361
Br J Haematol. 2020 Oct;191(2):282-290
pubmed: 32656767
J Clin Med. 2017 Apr 17;6(4):
pubmed: 28420167
Haemophilia. 2011 May;17(3):483-9
pubmed: 21118335
Haematologica. 2000 Oct;85(10 Suppl):48-50; discussion 50-1
pubmed: 11187871
Transfus Apher Sci. 2019 Oct;58(5):578-589
pubmed: 31447396
J Thromb Haemost. 2015 Nov;13(11):1980-8
pubmed: 26382916
Blood Adv. 2019 Dec 6;3(Suppl 1):48-50
pubmed: 31809542
J Thromb Haemost. 2011 Nov;9(11):2229-34
pubmed: 21883884
Thromb Haemost. 2021 Jul;121(7):891-899
pubmed: 33423244
Haemophilia. 2020 Aug;26 Suppl 6:1-158
pubmed: 32744769
Blood. 1995 Aug 1;86(3):983-8
pubmed: 7620189
Haemophilia. 2019 Jul;25(4):676-684
pubmed: 31033112
N Engl J Med. 1988 Apr 14;318(15):947-50
pubmed: 3127711
Haemophilia. 2001 Mar;7(2):154-9
pubmed: 11260274
Vox Sang. 1999;77 Suppl 1:49-54
pubmed: 10529689
Blood. 2012 Feb 9;119(6):1335-44
pubmed: 22101900
Semin Thromb Hemost. 2018 Sep;44(6):561-567
pubmed: 29220854
Vox Sang. 1996;70 Suppl 1:30-5
pubmed: 8869466
Cad Saude Publica. 2018 Oct 11;34(10):e00000218
pubmed: 30328994
J Pharm Policy Pract. 2016 Feb 08;9:3
pubmed: 26862438
Haemophilia. 2009 Jan;15(1):320-8
pubmed: 18976249
Int J Environ Res Public Health. 2020 Dec 30;18(1):
pubmed: 33396748
Haemophilia. 2000 May;6(3):150-7
pubmed: 10792472
Haemophilia. 2007 Mar;13(2):121-3
pubmed: 17286763
J Thromb Haemost. 2008 May;6(5):830-6
pubmed: 18284600
Int J Lab Hematol. 2018 Dec;40(6):621-629
pubmed: 29979821
J Thromb Haemost. 2009 Nov;7(11):1809-15
pubmed: 19740093
Blood Rev. 2018 Jul;32(4):326-338
pubmed: 29482894
Value Health. 2014 Sep;17(6):744-8
pubmed: 25236999
Blood. 2017 Dec 7;130(23):2463-2468
pubmed: 29042366
J Intern Med. 2015 Jan;277(1):1-15
pubmed: 25169114
Expert Rev Hematol. 2021 Feb;14(2):143-148
pubmed: 33499681
Thromb Haemost. 2016 May 2;115(5):872-95
pubmed: 26842562
Semin Thromb Hemost. 2009 Nov;35(8):735-51
pubmed: 20169510
Ann Intern Med. 1973 Jul;79(1):84-7
pubmed: 4124485
Haemophilia. 2019 Nov;25(6):1003-1010
pubmed: 31603594
Haematologica. 2001 Nov;86(11):1186-93
pubmed: 11694405
Vox Sang. 1999;77 Suppl 1:28-30
pubmed: 10529683
Haemophilia. 1999 Nov;5(6):431-5
pubmed: 10583531
Thromb Haemost. 2002 Jan;87(1):52-7
pubmed: 11848456
Cien Saude Colet. 2020 May;25(5):1955-1966
pubmed: 32402025
Haemophilia. 2010 May;16(102):71-9
pubmed: 20536988
Haemophilia. 2014 Jan;20(1):83-91
pubmed: 24354480
Haemophilia. 2020 Jul;26(4):631-636
pubmed: 32311809