Predictors of immune tolerance induction success in 231 children with severe hemophilia A with high-titer inhibitors – lessons learned from the PedNet prospective cohort study

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F65269705%3A_____%2F25%3A00082611" target="_blank" >RIV/65269705:_____/25:00082611 - isvavai.cz</a>

Výsledek na webu

<a href="https://www.sciencedirect.com/science/article/abs/pii/S1538783625004337" target="_blank" >https://www.sciencedirect.com/science/article/abs/pii/S1538783625004337</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.jtha.2025.07.010" target="_blank" >10.1016/j.jtha.2025.07.010</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Predictors of immune tolerance induction success in 231 children with severe hemophilia A with high-titer inhibitors – lessons learned from the PedNet prospective cohort study

Popis výsledku v původním jazyce

Background: Previously untreated patients with severe hemophilia A exposed to factor (F)VIII are at risk of developing high-titer inhibitors. Traditionally, such children were tried on immune tolerance induction (ITI). With availability of nonfactor therapies, recommendations regarding whether to continue trying ITI and how are lacking. Objectives: To provide data to address these questions, we reviewed the experience of ITI in Pediatric Network (PedNet) centers. Methods: The outcomes of 231 previously untreated patients with severe hemophilia A and high-titer inhibitors to FVIII, who were followed over a 20-year period and underwent GREATER-THAN OR EQUAL TO1 course of ITI, were reviewed. Results: The success of the first course of ITI was predicted by pre-ITI peak inhibitor titers (PITs), a family history of inhibitors, high-risk F8 gene variants, and the start of ITI within 10 months of inhibitor diagnosis. Pre-ITI PITs were a strong predictor of eventual ITI success with 1 or more ITI courses: 76.4% of those with pre-ITI PITs of 5 to 39 Bethesda Units (BUs) achieved tolerance (median, 0.72 years) vs 70.9% of those with pre-ITI PITs of 40 to 200 BU (median, 2.1 years) vs 42.1% of those with pre-ITI PITs of &gt;200 BU (median, 5.1 years). A PIT of &gt;200 BU during the first course of ITI was a strong predictor of ultimately failing ITI. The ITI regimen, whether administered daily or nondaily at a high or low dose, was not a predictor of ITI success with the first course of ITI. Conclusion: These predictors of success may be used to decide whether and how to initiate ITI when nonreplacement prophylaxis is available.

Název v anglickém jazyce

Predictors of immune tolerance induction success in 231 children with severe hemophilia A with high-titer inhibitors – lessons learned from the PedNet prospective cohort study

Popis výsledku anglicky

Background: Previously untreated patients with severe hemophilia A exposed to factor (F)VIII are at risk of developing high-titer inhibitors. Traditionally, such children were tried on immune tolerance induction (ITI). With availability of nonfactor therapies, recommendations regarding whether to continue trying ITI and how are lacking. Objectives: To provide data to address these questions, we reviewed the experience of ITI in Pediatric Network (PedNet) centers. Methods: The outcomes of 231 previously untreated patients with severe hemophilia A and high-titer inhibitors to FVIII, who were followed over a 20-year period and underwent GREATER-THAN OR EQUAL TO1 course of ITI, were reviewed. Results: The success of the first course of ITI was predicted by pre-ITI peak inhibitor titers (PITs), a family history of inhibitors, high-risk F8 gene variants, and the start of ITI within 10 months of inhibitor diagnosis. Pre-ITI PITs were a strong predictor of eventual ITI success with 1 or more ITI courses: 76.4% of those with pre-ITI PITs of 5 to 39 Bethesda Units (BUs) achieved tolerance (median, 0.72 years) vs 70.9% of those with pre-ITI PITs of 40 to 200 BU (median, 2.1 years) vs 42.1% of those with pre-ITI PITs of &gt;200 BU (median, 5.1 years). A PIT of &gt;200 BU during the first course of ITI was a strong predictor of ultimately failing ITI. The ITI regimen, whether administered daily or nondaily at a high or low dose, was not a predictor of ITI success with the first course of ITI. Conclusion: These predictors of success may be used to decide whether and how to initiate ITI when nonreplacement prophylaxis is available.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30205 - Hematology

Projekt

—

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2025

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Journal of Thrombosis and Haemostasis

ISSN

1538-7933

e-ISSN

1538-7836

Svazek periodika

23

Číslo periodika v rámci svazku

10

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

4

Strana od-do

3134-3147

Kód UT WoS článku

001585803600003

EID výsledku v databázi Scopus

2-s2.0-105013147076