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. 2022 Nov;20(11):2526-2537.
doi: 10.1111/jth.15878. Epub 2022 Sep 26.

Time between inhibitor detection and start of immune tolerance induction: Association with outcome in the BrazIT study

Ricardo Mesquita Camelo  1   2 , Maíse Moreira Dias  1 , Camila Caram-Deelder  2   3 , Samantha Gouw  4 , Laura Peixoto de Magalhães  1 , Luciana Werneck Zuccherato  1 , Letícia Lemos Jardim  1   2 , Andrea Gonçalves de Oliveira  5 , Rosângela de Albuquerque Ribeiro  6   7 , Vivian Karla Brognoli Franco  8 , Maria do Rosário Ferraz Roberti  9   10 , Fábia Michelle Rodrigues de Araújo Callado  11 , Leina Yukari Etto  12   13 , Maria Aline Ferreira de Cerqueira  14 , Mônica Hermida Cerqueira  15 , Cláudia Santos Lorenzato  16 , Ieda Solange de Souza  17   18 , Édvis Santos Soares Serafim  19   20 , Andrea Aparecida Garcia  21   22 , Tânia Hissa Anegawa  23   24 , Daniele Campos Fontes Neves  25   26 , Doralice Marvulle Tan  27 , Johanna van der Bom  2 , Suely Meireles Rezende  1 ; Brazilian Immune Tolerance (BrazIT) Study group
Affiliations
Free article

Time between inhibitor detection and start of immune tolerance induction: Association with outcome in the BrazIT study

Ricardo Mesquita Camelo et al. J Thromb Haemost. 2022 Nov.
Free article

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.

Keywords: hemophilia A; immune tolerance induction; inhibitor; outcome; risk factor.

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References

REFERENCES

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