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664 Characteristics Associated with the Success of Immune Tolerance Induction Among People with Severe Hemophilia a in the United States

Program: Oral and Poster Abstracts
Type: Oral
Session: 901. Health Services and Quality Improvement – Non-Malignant Conditions: Raising the bar in Anemia, Bleeding, and Thrombotic Disorders
Sunday, December 10, 2023: 5:15 PM

Stacey Fedewa, PhD, MPH1*, Amanda B. Payne, PhD, MPH2, Lorraine Cafuir, MD3, Duc Quang Tran, MD, MSc3, Ana G. Antun, MD4 and Christine Kempton, MD3

1Department of Hematology and Medical Oncology and Hemophilia of Georgia Center for Bleeding & Clotting Disorders at Emory, Emory University, Atlanta, GA
2Centers For Disease Control and Prevention, Atlanta, GA
3Emory University, Atlanta, GA
4Emory University, Decatur, GA

Introduction: Immune tolerance induction (ITI) is the only treatment to eradicate inhibitors in people with severe hemophilia A with inhibitors (PwSHAi). An earlier study reported lower receipt of ITI treatment in non-Hispanic (NH) Black and Hispanic compared to NH White PwSHAi (Kempton CL, 2022). Since risk of inhibitor development is greater among Black and Hispanic persons with hemophilia, it has been hypothesized that race and ethnicity may impact the success of ITI. Limited studies have evaluated this hypothesis. This study examined the success of ITI by race and ethnicity among PwSHAi in the Community Counts (CC) Registry between 2013-2017 in the United States (US).

Methods: This cross-sectional study used data from the CC Registry, which is a collaboration of the American Thrombosis & Hemostasis Network (ATHN), Centers for Disease Control and Prevention (CDC), and the Hemophilia Center Network (HTCN) using ATHN Study Manager. The CC Registry collects data from people who received care from >135 US hemophilia treatment centers (HTCs). PwSHAi who entered the CC Registry between 2013-2017 and received ITI were selected (n=679); those who were <3 years old at Registry enrollment (n=41) and had history of an inhibitor for <3 years (n=79) were excluded, resulting in 559 people were available for the analyses. Data from 2013-2017 were chosen to represent the pre-emicizumab era where ITI was the standard of care without debate. The 3-year age and inhibitor history cut-point was chosen to ensure ample time for PwSHAi to receive and respond to ITI. The primary outcome was ITI response defined as 1) successful (PwSHAi receiving FVIII replacement therapy at standard doses); 2) partially successful (receiving FVIII replacement therapy at increased dosing); and 3) failed (receiving bypassing agents). Primary independent variables included race/ethnicity, likelihood of ITI success defined with pre-ITI peak inhibitor values alone, grouped as very good [<25 Bethesda Units (BU)], good (25-199 BU), poor (200-999 BU), and very poor (≥1000 BU) prognosis, based on the Future of Immunotolerance Treatment (FIT) group’s recent management algorithm (Carcao, 2019). Unadjusted (PR) and adjusted prevalence ratios (aPR) and corresponding 95% confidence intervals (CI) were computed with logistic models with predicted marginals.

Results: Among 559 PwSHAi included, 318 (56.9%) were NH White, 107 (19.1%) were NH Black, 101 (18.1%) were Hispanic, 24 (4.3%) were Asian, and 9 (1.7%) were coded as other or missing (Table 1). The median age at Registry enrollment and inhibitor detection was 16 years and 2 years, respectively. Approximately 64% of NH Black, Hispanic, and NH White PwSHAi had either good or very good prognosis, though less than half (41.7%) of Asian PwSHAi had very good or good prognosis.

While 59.7% of PwSHAi achieved successful ITI, 20.7% and 19.5% only achieved partially successful or experienced failed ITI, respectively (Table 1). Success of ITI linearly increased according to prognostic group where 21.7%, 36.3%, 55.6% and 69.6% of those with very poor, poor, good, and very good prognosis achieved successful ITI, respectively (χ2 p-value<.001, Cochran-Armitage Trend p-value<.001). The proportion with successful ITI was non-significantly lower in NH Black (54.2%; PR=0.87,95%CI 0.71,1.05), Hispanic (55.4%; PR=0.89,95%CI 0.73,1.08), and Asian (58.3%; PR=0.93, 95%CI 0.66,1.32) PwSHAi relative to NH White (62.6%) PwSHAi in both crude and adjusted analyses (Table 2). In analyses restricted to those PwSHAi with very good or good prognosis, successful ITI prevalence was nearly identical in NH Black (63.8%) and NH White (64.9%). ITI success was similar across age at inhibitor detection, registry enrollment, health insurance and HTC size (Table 2).

Conclusion: Using US CC Registry data, approximately 60% of PwSHAi treated with ITI had a successful response, a proportion similar to previous studies. The proportion of PwSHAi who had successful ITI linearly improved with predicted prognosis, defined by the peak inhibitor titer alone. In our study, prognosis category was generally similar in Hispanic, NH White, and NH Black PwSHAi and the proportion with successful ITI did not vary significantly according to race/ethnicity. These findings do not support the hypothesis that ITI response varies according to race/ethnicity, and it suggests that the benefits of ITI are similar across race and ethnicity.

Disclosures: Tran: Bayer, Biomarin, HEMA Biologics, Genentech, Takeda, and UniQure. He has been a consultant for Bayer and Novo Nordisk: Other: medical advisory boards. Kempton: Spark Therapuetics: Honoraria; Pfizer: Honoraria; BioMarin: Honoraria; Takeda: Honoraria; Sanofi US: Honoraria; Genetech: Honoraria.

*signifies non-member of ASH