Abstract
Background: Immune tolerance induction (ITI) is the treatment of choice for eradication of anti-factor VIII (FVIII) neutralizing alloantibodies (inhibitors) in people with inherited hemophilia A and high-responding inhibitor (PwHA-HRi). The association between ITI outcome and time elapsed between inhibitor detection and start of ITI (∆tinhi-ITI) is debatable. Objective: The aim of this study was to evaluate this association among a large cohort of severe PwHA-HRi. Methods: Severe (factor VIII activity level <1%) PwHA-HRi on ITI (n = 142) were enrolled in 15 hemophilia treatment centers. PwHA-HRi were treated according to the Brazilian ITI Protocol. ITI outcomes were defined as success (i.e., recovered responsiveness to exogenous FVIII) and failure (i.e., no responsiveness to exogenous FVIII and requirement of bypassing agents to control bleeding). Results: Median ages at inhibitor detection and at ITI start were 3.2 years (interquartile range [IQR], 1.6–8.1) and 6.9 years [IQR, 2.6–20.1), respectively. PwHA-HRi were stratified according to ∆tinhi-ITI quartiles: first (0.0–0.6 year), second (>0.6–1.7 year), third (>1.7–9.2 years), and fourth quartile (>9.2–24.5 years). The overall success rate was 65.5% (93/142), with no difference among first, second, third, and fourth quartiles (62.9%, 69.4%, 58.3%, and 71.4%, respectively) even after adjusting the analyses for potential confounders. Conclusion: In conclusion, delayed ITI start is not associated with failure of ITI in PwHA-HRi. Therefore, ITI should be offered for these patients, regardless of the time elapsed between the detection of inhibitor and the ITI start.
Original language | English |
---|---|
Pages (from-to) | 2526-2537 |
Number of pages | 12 |
Journal | Journal of thrombosis and haemostasis |
Volume | 20 |
Issue number | 11 |
Early online date | 2022 |
DOIs | |
Publication status | Published - 1 Nov 2022 |
Keywords
- hemophilia A
- immune tolerance induction
- inhibitor
- outcome
- risk factor
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In: Journal of thrombosis and haemostasis, Vol. 20, No. 11, 01.11.2022, p. 2526-2537.
Research output: Contribution to journal › Article › Academic › peer-review
TY - JOUR
T1 - Time between inhibitor detection and start of immune tolerance induction
T2 - Association with outcome in the BrazIT study
AU - Camelo, Ricardo Mesquita
AU - Dias, Maíse Moreira
AU - Caram-Deelder, Camila
AU - Gouw, Samantha
AU - de Magalhães, Laura Peixoto
AU - Zuccherato, Luciana Werneck
AU - Jardim, Letícia Lemos
AU - de Oliveira, Andrea Gonçalves
AU - de Albuquerque Ribeiro, Rosângela
AU - Franco, Vivian Karla Brognoli
AU - do Rosário Ferraz Roberti, Maria
AU - de Araújo Callado, F. bia Michelle Rodrigues
AU - Etto, Leina Yukari
AU - de Cerqueira, Maria Aline Ferreira
AU - Cerqueira, M. nica Hermida
AU - Lorenzato, Cláudia Santos
AU - de Souza, Ieda Solange
AU - Serafim, Édvis Santos Soares
AU - Garcia, Andrea Aparecida
AU - Anegawa, T. nia Hissa
AU - Neves, Daniele Campos Fontes
AU - the Brazilian Immune Tolerance (BrazIT) Study group
AU - Tan, Doralice Marvulle
AU - van der Bom, Johanna
AU - Rezende, Suely Meireles
N1 - Funding Information: The BrazIT Study group would like to thank the multiprofessional team from the participating HTCs for providing support to identify and refer patients to the study. The BrazIT Study is fully funded by governmental grants from the National Health Fund (grant number 17217.9850001-15-006) and CNPq (grant number 420008/2018-7). RMC received a scholarship (PDSE-88881.362041/2019-1) from the CAPES Foundation, an agency under the Ministry of Education of Brazil, to conduct part of his doctoral research as a visiting student at Leiden Universitair Medisch Centrum in the Netherlands. MMD received a scholarship (PIBIC-155139/2019-3) from CNPq. LPM received a scholarship (PROBIC-14020) from FAPEMIG. LWZ received a scholarship (PNPD Program) from CAPES Foundation. Funding Information: The BrazIT Study is fully funded by governmental grants from the National Health Fund (grant number 17217.9850001–15‐006) and CNPq (grant number 420008/2018–7). RMC received a scholarship (PDSE‐88881.362041/2019–1) from the CAPES Foundation, an agency under the Ministry of Education of Brazil, to conduct part of his doctoral research as a visiting student at Leiden Universitair Medisch Centrum in the Netherlands. MMD received a scholarship (PIBIC‐155139/2019–3) from CNPq. LPM received a scholarship (PROBIC‐14020) from FAPEMIG. LWZ received a scholarship (PNPD Program) from CAPES Foundation. Funding Information: RMC received speaker fees from Bayer, NovoNordisk, Hoffman‐La Roche, and Takeda; consultancy fees from Hoffman‐La Roche and Takeda, and scientific event grants from Bayer, NovoNordisk, Hoffman‐La Roche, and Takeda. SG received an unrestricted research grant from Sobi. AGO received speaker fees from Hoffman‐La Roche, Takeda and NovoNordisk, and scientific event grants from NovoNordisk. VKBF received scientific event grants from Takeda. MRFR received speaker fees from NovoNordisk, scientific event grants from Hoffman‐La Roche, Takeda and NovoNordisk, and consultancy fees from the Brazilian Ministry of Health. FMRAC received scientific event grants from Hoffman‐La Roche and NovoNordisk. LYE received scientific event grants from Hoffman‐La Roche. MAFC received scientific event grants from NovoNordisk. ISSP received speaker fees from Hoffman‐La Roche and Takeda, scientific event grants from Hoffman‐La Roche, Takeda and NovoNordisk, consultancy fees from the Hoffman‐La Roche, NovoNordisk, Bayer and Biomarin, and grants for scientifical publication from Takeda. ESSS received scientific event grants from NovoNordisk. AAG received speaker fees from Takeda and NovoNordisk, scientific event grants from Takeda and NovoNordisk, and consultancy fees from NovoNordisk. THA received scientific event grants from Hoffman‐La Roche and Takeda. DCFN received scientific event grants from Takeda. JvdB received reimbursement for educational activities from Bayer and unrestricted grants from NovoNordisk. MMD, CCD, LPM, LWZ, LLJ, RAR, MHC, CSL, DMT, and SMR declare they have no competing interests which might be perceived as posing a conflict of bias. Funding Information: The BrazIT Study group would like to thank the multiprofessional team from the participating HTCs for providing support to identify and refer patients to the study. The BrazIT Study is fully funded by governmental grants from the National Health Fund (grant number 17217.9850001‐15‐006) and CNPq (grant number 420008/2018‐7). RMC received a scholarship (PDSE‐88881.362041/2019‐1) from the CAPES Foundation, an agency under the Ministry of Education of Brazil, to conduct part of his doctoral research as a visiting student at Leiden Universitair Medisch Centrum in the Netherlands. MMD received a scholarship (PIBIC‐155139/2019‐3) from CNPq. LPM received a scholarship (PROBIC‐14020) from FAPEMIG. LWZ received a scholarship (PNPD Program) from CAPES Foundation. Publisher Copyright: © 2022 International Society on Thrombosis and Haemostasis.
PY - 2022/11/1
Y1 - 2022/11/1
N2 - Background: Immune tolerance induction (ITI) is the treatment of choice for eradication of anti-factor VIII (FVIII) neutralizing alloantibodies (inhibitors) in people with inherited hemophilia A and high-responding inhibitor (PwHA-HRi). The association between ITI outcome and time elapsed between inhibitor detection and start of ITI (∆tinhi-ITI) is debatable. Objective: The aim of this study was to evaluate this association among a large cohort of severe PwHA-HRi. Methods: Severe (factor VIII activity level <1%) PwHA-HRi on ITI (n = 142) were enrolled in 15 hemophilia treatment centers. PwHA-HRi were treated according to the Brazilian ITI Protocol. ITI outcomes were defined as success (i.e., recovered responsiveness to exogenous FVIII) and failure (i.e., no responsiveness to exogenous FVIII and requirement of bypassing agents to control bleeding). Results: Median ages at inhibitor detection and at ITI start were 3.2 years (interquartile range [IQR], 1.6–8.1) and 6.9 years [IQR, 2.6–20.1), respectively. PwHA-HRi were stratified according to ∆tinhi-ITI quartiles: first (0.0–0.6 year), second (>0.6–1.7 year), third (>1.7–9.2 years), and fourth quartile (>9.2–24.5 years). The overall success rate was 65.5% (93/142), with no difference among first, second, third, and fourth quartiles (62.9%, 69.4%, 58.3%, and 71.4%, respectively) even after adjusting the analyses for potential confounders. Conclusion: In conclusion, delayed ITI start is not associated with failure of ITI in PwHA-HRi. Therefore, ITI should be offered for these patients, regardless of the time elapsed between the detection of inhibitor and the ITI start.
AB - Background: Immune tolerance induction (ITI) is the treatment of choice for eradication of anti-factor VIII (FVIII) neutralizing alloantibodies (inhibitors) in people with inherited hemophilia A and high-responding inhibitor (PwHA-HRi). The association between ITI outcome and time elapsed between inhibitor detection and start of ITI (∆tinhi-ITI) is debatable. Objective: The aim of this study was to evaluate this association among a large cohort of severe PwHA-HRi. Methods: Severe (factor VIII activity level <1%) PwHA-HRi on ITI (n = 142) were enrolled in 15 hemophilia treatment centers. PwHA-HRi were treated according to the Brazilian ITI Protocol. ITI outcomes were defined as success (i.e., recovered responsiveness to exogenous FVIII) and failure (i.e., no responsiveness to exogenous FVIII and requirement of bypassing agents to control bleeding). Results: Median ages at inhibitor detection and at ITI start were 3.2 years (interquartile range [IQR], 1.6–8.1) and 6.9 years [IQR, 2.6–20.1), respectively. PwHA-HRi were stratified according to ∆tinhi-ITI quartiles: first (0.0–0.6 year), second (>0.6–1.7 year), third (>1.7–9.2 years), and fourth quartile (>9.2–24.5 years). The overall success rate was 65.5% (93/142), with no difference among first, second, third, and fourth quartiles (62.9%, 69.4%, 58.3%, and 71.4%, respectively) even after adjusting the analyses for potential confounders. Conclusion: In conclusion, delayed ITI start is not associated with failure of ITI in PwHA-HRi. Therefore, ITI should be offered for these patients, regardless of the time elapsed between the detection of inhibitor and the ITI start.
KW - hemophilia A
KW - immune tolerance induction
KW - inhibitor
KW - outcome
KW - risk factor
UR - http://www.scopus.com/inward/record.url?scp=85138920222&partnerID=8YFLogxK
U2 - https://doi.org/10.1111/jth.15878
DO - https://doi.org/10.1111/jth.15878
M3 - Article
C2 - 36102352
SN - 1538-7933
VL - 20
SP - 2526
EP - 2537
JO - Journal of thrombosis and haemostasis
JF - Journal of thrombosis and haemostasis
IS - 11
ER -