Abstract
Introduction: Immune tolerance induction (ITI) was the primary therapeutic approach to eradicate inhibitors in haemophilia patients. Several large ITI registries had been reported, but successful predictors of ITI outcome are still debated. No reports are available on large ITI studies in non-caucasian countries. Aim: We designed a retrospective cohort study of ITI in Japanese haemophilia patients with inhibitor. Methods: Retrospective data were collected from 155 haemophilia (H)A (140 severe-type) and 7 HB (7 severe-type) patients treated at 45 institutions. ITI outcome was centrally reviewed. We defined “success” as undetectable inhibitor after 2 consecutive measurements. Results: The ITI success rate was 71.2% for HA and 83.3% for HB. Cumulated success rates for HA achieving 50% and 75% were 0.7 and 2 years after treatment, respectively. Significant successful predictors in HA were low-responding inhibitors compared to high-responding inhibitors, shorter time to the start of ITI, and lower historical and treatment peak titres of inhibitor. Dose regimen (high dose; ≥90 IU/kg every day, low dose; ≤75 IU/kg, 3 d/wk) and the type of therapeutic product did not affect outcomes. The success rate of salvage ITI using von Willebrand factor-containing factor VIII was 50% (n = 6/12), and patient age at the start of salvage ITI was a significant predictor. The inhibitor recurred in 6 HA cases (3.9%). Conclusion: The results provided potentially important information for improving future success rates for ITI in inhibitor patients.
| Original language | English |
|---|---|
| Pages (from-to) | e328-e337 |
| Journal | Haemophilia |
| Volume | 24 |
| Issue number | 5 |
| DOIs | |
| Publication status | Published - Sep 1 2018 |
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All Science Journal Classification (ASJC) codes
- Hematology
- Genetics(clinical)
Cite this
The Japanese Immune Tolerance Induction (J-ITI) study in haemophilia patients with inhibitor : Outcomes and successful predictors of ITI treatment. / Nogami, K.; Taki, M.; Matsushita, T.; Ohga, Shoichi; Oka, T.; Horikoshi, Y.; Amano, K.; Shima, M.
In: Haemophilia, Vol. 24, No. 5, 01.09.2018, p. e328-e337.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - The Japanese Immune Tolerance Induction (J-ITI) study in haemophilia patients with inhibitor
T2 - Outcomes and successful predictors of ITI treatment
AU - Nogami, K.
AU - Taki, M.
AU - Matsushita, T.
AU - Ohga, Shoichi
AU - Oka, T.
AU - Horikoshi, Y.
AU - Amano, K.
AU - Shima, M.
PY - 2018/9/1
Y1 - 2018/9/1
N2 - Introduction: Immune tolerance induction (ITI) was the primary therapeutic approach to eradicate inhibitors in haemophilia patients. Several large ITI registries had been reported, but successful predictors of ITI outcome are still debated. No reports are available on large ITI studies in non-caucasian countries. Aim: We designed a retrospective cohort study of ITI in Japanese haemophilia patients with inhibitor. Methods: Retrospective data were collected from 155 haemophilia (H)A (140 severe-type) and 7 HB (7 severe-type) patients treated at 45 institutions. ITI outcome was centrally reviewed. We defined “success” as undetectable inhibitor after 2 consecutive measurements. Results: The ITI success rate was 71.2% for HA and 83.3% for HB. Cumulated success rates for HA achieving 50% and 75% were 0.7 and 2 years after treatment, respectively. Significant successful predictors in HA were low-responding inhibitors compared to high-responding inhibitors, shorter time to the start of ITI, and lower historical and treatment peak titres of inhibitor. Dose regimen (high dose; ≥90 IU/kg every day, low dose; ≤75 IU/kg, 3 d/wk) and the type of therapeutic product did not affect outcomes. The success rate of salvage ITI using von Willebrand factor-containing factor VIII was 50% (n = 6/12), and patient age at the start of salvage ITI was a significant predictor. The inhibitor recurred in 6 HA cases (3.9%). Conclusion: The results provided potentially important information for improving future success rates for ITI in inhibitor patients.
AB - Introduction: Immune tolerance induction (ITI) was the primary therapeutic approach to eradicate inhibitors in haemophilia patients. Several large ITI registries had been reported, but successful predictors of ITI outcome are still debated. No reports are available on large ITI studies in non-caucasian countries. Aim: We designed a retrospective cohort study of ITI in Japanese haemophilia patients with inhibitor. Methods: Retrospective data were collected from 155 haemophilia (H)A (140 severe-type) and 7 HB (7 severe-type) patients treated at 45 institutions. ITI outcome was centrally reviewed. We defined “success” as undetectable inhibitor after 2 consecutive measurements. Results: The ITI success rate was 71.2% for HA and 83.3% for HB. Cumulated success rates for HA achieving 50% and 75% were 0.7 and 2 years after treatment, respectively. Significant successful predictors in HA were low-responding inhibitors compared to high-responding inhibitors, shorter time to the start of ITI, and lower historical and treatment peak titres of inhibitor. Dose regimen (high dose; ≥90 IU/kg every day, low dose; ≤75 IU/kg, 3 d/wk) and the type of therapeutic product did not affect outcomes. The success rate of salvage ITI using von Willebrand factor-containing factor VIII was 50% (n = 6/12), and patient age at the start of salvage ITI was a significant predictor. The inhibitor recurred in 6 HA cases (3.9%). Conclusion: The results provided potentially important information for improving future success rates for ITI in inhibitor patients.
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U2 - 10.1111/hae.13531
DO - 10.1111/hae.13531
M3 - Article
C2 - 29902361
AN - SCOPUS:85053838042
VL - 24
SP - e328-e337
JO - Haemophilia
JF - Haemophilia
SN - 1351-8216
IS - 5
ER -