Race, Ethnicity Do Not Impact Immune Tolerance Induction Success, Study Finds

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Findings from a cross-sectional study showed equal immune tolerance induction success rates among patients with severe hemophilia A, regardless of race or ethnicity.

Approximately 60% of participants treated with immune tolerance induction had a successful response, a proportion that improved linearly with predicted prognosis and did not vary significantly according to race/ethnicity. Results were presented at the 2023 American Society of Hematology (ASH) Annual Meeting and Exposition in San Diego, California.¹

“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,” wrote Stacey Fedewa, PhD, MPH, assistant professor in the department of hematology and medical oncology and hemophilia of Georgia Center for Bleeding and Clotting Disorders at Emory University, and colleagues.¹

An inherited bleeding disorder in which the blood does not clot properly, hemophilia affects 20,000-33,000 males in the United States. The US Centers for Disease Control and Prevention estimates about 15-20% of people with hemophilia develop an inhibitor that prevents clotting factors from functioning properly, making it more difficult to stop a bleeding episode. Although race and ethnicity have been identified as potential risk factors for inhibitor development, little is known about their association with treatment outcomes.²

To examine the success of immune tolerance induction by race and ethnicity among people with severe hemophilia A with inhibitors, investigators collected data for 679 patients who entered the Community Counts Registry between 2013-2017 and received immune tolerance induction. A collaboration between the American Thrombosis and Hemostasis Network, the US Centers for Disease Control and Prevention, and the Hemophilia Center Network, the Community Counts Registry collects data from >135 US hemophilia treatment centers.¹

People with severe hemophilia A with inhibitors < 3 years of age at Registry enrollment (n = 41) and with < 3 years of history of an inhibitor (n=79) were excluded to ensure ample time to receive and respond to immune tolerance induction. The remaining 559 patients were included in the study. Among the cohort, 318 (56.9%) participants were non-Hispanic White, 107 (19.1%) were non-Hispanic Black, 101 (18.1%) were Hispanic, 24 (4.3%) were Asian, and 9 (1.7%) were coded as other or missing. The median age at Registry enrollment and inhibitor detection was 16 years and 2 years, respectively.¹

The primary outcome was immune tolerance induction response, which investigators defined as successful (receiving FVIII replacement therapy at standard doses), partially successful (receiving FVIII replacement therapy at increased dosing), and failed (receiving bypassing agents). Primary independent variables included race/ethnicity and the likelihood of immune tolerance induction success, defined using pre-immune tolerance induction peak inhibitor values alone. Values were grouped as very good (<25 Bethesda Units [BU]), good (25-199 BU), poor (200-999 BU), and very poor (≥1000 BU).¹

Investigators noted approximately 64% of non-Hispanic Black, Hispanic, and non-Hispanic White participants had either good or very good prognoses, but less than half (41.7%) of Asian participants had these prognoses. In total, 59.7% of participants achieved successful immune tolerance induction, while 20.7% and 19.5% achieved partially successful or experienced failed immune tolerance induction, respectively.¹

Upon analysis, the success of immune tolerance induction increased according to participants’ prognostic group, with 21.7%, 36.3%, 55.6%, and 69.6% of those with very poor, poor, good, and very good prognosis achieving successful immune tolerance induction, respectively (χ2 P < .001; Cochran-Armitage Trend P < .001).¹

The proportion of participants with successful immune tolerance induction was lower in non-Hispanic Black (54.2%; prevalence ratio [PR], 0.87; 95% Confidence interval [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) participants relative to non-Hispanic White (62.6%) participants in both crude and adjusted analyses, although investigators pointed out this finding was not statistically significant.¹

In analyses restricted to patients with good or very good prognoses, successful immune tolerance induction prevalence was similar between non-Hispanic Black (63.8%) and non-Hispanic White (64.9%) participants. Of note, immune tolerance induction success was similar across age at inhibitor detection, Registry enrollment, health insurance, and HTC size.¹

“In our study, prognosis category was generally similar in Hispanic, non-Hispanic White, and non-Hispanic Black people with severe hemophilia A with inhibitors and the proportion with successful immune tolerance induction did not vary significantly according to race/ethnicity. These findings do not support the hypothesis that immune tolerance induction response varies according to race/ethnicity, and it suggests that the benefits of immune tolerance induction are similar across race and ethnicity,” investigators concluded.¹

References:

1. Fedewa S, Payne AB, Cafuir L, et al. 664 Characteristics Associated with the Success of Immune Tolerance Induction Among People with Severe Hemophilia a in the United States. Presented at: ASH Annual Meeting and Exposition. San Diego, CA. December 9-12, 2023.
2. US Centers for Disease Control and Prevention. What is Hemophilia? Hemophilia. October 24, 2023. Accessed December 10, 2023. https://www.cdc.gov/ncbddd/hemophilia/facts.html