Low-dose immune tolerance induction therapy in severe hemophilia a children in China: Starting earlier resulted in better inhibitor eradication outcomes

Thromb Res. 2023 May:225:33-38. doi: 10.1016/j.thromres.2023.02.016. Epub 2023 Mar 5.

Abstract

Background: Shorter interval-time from inhibitor detection to starting immune tolerance induction (ITI) might predict better ITI outcomes for severe Hemophilia A (SHA) patients with high-risk-inhibitors. However, the prediction-impact of interval-time for these patients on low-dose ITI strategy remained unclear.

Objectives: To explore the relationship between interval-time and low-dose ITI outcomes in Chinese SHA children with high-risk-inhibitors.

Methods: This was a single-center, retrospective study on SHA children with high-risk-inhibitors (each with immediate pre-ITI inhibitor titer>10 Bethesda Units/mL) undergoing low-dose ITI strategy for ≥24 months. ITI outcomes and their predictive factors were evaluated at the 24th month treatment for each patient. The predictive ability of interval-time on ITI success was determined using receiver operating characteristic (ROC) curve.

Results: Among 47 patients investigated, 34 (72.3 %) achieved success. Independent predictor for ITI-outcome on multivariate analysis included the interval-time (p = 0.007) and peak inhibitor-titer (p = 0.011). Shorter interval-time predicted ITI success [cut-off value = 22.3 months, area under ROC-curve (AUC) = 0.701] and early-ITI success within 12 month (cut-off value = 9.4 months AUC = 0.704). Linear regression analysis suggested each month interval-time delay delayed success by 0.1552 month. Unlike the interval-time, peak inhibitor-titer had no success-predictive value in high-peak inhibitor-titer patients on ITI with immunosuppressants.

Conclusions: Interval-time represented a strong predictive value for outcomes in our low-dose ITI strategy for SHA patients with high-risk-inhibitors. Shorter interval-time was associated with higher success rate and earlier success achievement. The respective interval-time cut-off values were 22.3 months for ITI success and 9.4 months for early-success.

Keywords: Children; Immune tolerance induction; Inhibitors; Low-dose; Severe hemophilia a; Time from inhibitor detection to starting ITI.

MeSH terms

  • Child
  • China
  • Factor VIII / therapeutic use
  • Hemophilia A* / complications
  • Hemophilia A* / drug therapy
  • Humans
  • Immune Tolerance
  • Retrospective Studies

Substances

  • Factor VIII