Race and ethnicity and the success of immune tolerance induction among people with severe haemophilia A in the United States.

INTRODUCTION: Immune tolerance induction (ITI) is the only treatment to eradicate inhibitors in people with severe haemophilia A with inhibitors. Since the risk of inhibitor development is greater among Black and Hispanic persons, it has been hypothesized that race and ethnicity may influence ITI success. Limited studies have evaluated this hypothesis. AIM: To examine the success of ITI according to race and ethnicity. METHODS: Participants who entered the Community Counts (CC) Registry between 2013 and 2017, were aged ≥3 years at study entry, and received ITI were included (n = 559). The proportion of participants with successful ITI was examined with adjusted prevalence ratios (aPRs) and corresponding 95% confidence intervals (95% CIs). RESULTS: Among 559 participants, 56.9%, 19.1%, 18.1% and 4.3% were Non-Hispanic (NH) White, NH Black, Hispanic and Asian, respectively, and 1.7% were coded as other or missing. Approximately 80% of Hispanic, NH Black and NH White participants had good/very good prognosis, defined as having a pre-ITI peak inhibitor of < 200 Bethesda Units per millilitre. Nearly 60% of participants (59.7%) achieved successful ITI, 20.7% and 19.5% experienced partially successful or failed ITI, respectively. Successful ITI was non-significantly lower in NH Black (54.2%; aPR = 0.95, 95% CI 0.62-1.44) and Hispanic (55.4%; aPR = 0.89, 95% CI 0.71-1.13) relative to NH White participants (62.6%). CONCLUSION: In this study, 60% of participants in the CC Registry had successful ITI, consistent with previous studies. The proportion with successful ITI was generally comparable across racial and ethnic groups with similar prognosis. These findings do not support the hypothesis that ITI response varies according to race or ethnicity.

Race and ethnicity reporting and representation in hemophilia clinical trials.

ABSTRACT: Racial and ethnic representativeness in clinical trials is crucial to mitigate disparities in outcomes; however, diversity among hemophilia trials is unknown. The aim of this study is to examine the reporting and representation of race and ethnicity in trials of people with hemophilia (PwH). In this cross-sectional study, the ClinicalTrials.gov database was queried in April 2023 for interventional clinical trials involving PwH between 2007 and 2022. The distribution of participants (observed) was compared with expected proportions based on US Hemophilia Treatment Center (HTC) and country-specific census data with observed-to-expected ratios (OERs). Of 129 trials included, 94.6% were industry sponsored, with a mean of 62 participants and mean age of 26.8 years. Overall, 52.0% (n = 66) of trials reported data on race and ethnicity, increasing from 13.9% in 2007-2012 to 22.5% in 2013-2016 to 100% in 2017-2022 (P = .001). Among these 66 trials, 65.8%, 22.8%, 5.1%, 3.9% of participants were White, Asian, Hispanic, and Black, respectively. OERs were 10% to 20% lower for White participants vs US HTC, and US, UK, and Canadian census populations and ∼75% lower for Black or Hispanic participants when compared with US HTC and US census population. OERs for Asian participants were 1.6 to 3 times higher than Canada, US, and UK census populations. The reporting of race and ethnicity in hemophilia trials has drastically improved; however, Black and Hispanic PwH remain especially underrepresented. To address these disparities, stakeholders across the clinical trial enterprise need to implement strategies to ensure equitable participation.

Defining the impact of immune tolerance induction on clinically relevant outcomes in a US cohort of severe hemophilia A.

ABSTRACT: Although the near-term benefit of immune tolerance induction (ITI) for the treatment of people with severe hemophilia A with inhibitor is apparent, the magnitude of the longer-term impact of ITI on clinical outcomes remains undefined. We examined the association between receiving ITI and the success of ITI on clinical outcomes including (1) clinical events, (2) health care use, (3) quality of life/function, (4) socioeconomic status, and (5) death, using the Community Counts (CC) registry of US Hemophilia Treatment Centers between 2013 and 2017. Multivariate logistic regression, negative binomial, and Poisson models were used. Included in this study were 3659 people with severe hemophilia A with median age of 21 years when entering the CC registry. Among 576 participants with inhibitors, 485 had received ITI (84%). ITI was successful in 299 (61.7%) and partially successful or failed in 95 (19.5%) or 91 (18.7%), respectively. Those that received ITI had fewer treated bleeds, less chronic pain, better function, and higher educational attainment than those not receiving ITI. Successful vs partially successful and failed ITI was associated with fewer treated bleeds, less health care use, less chronic pain, better function, and fewer missed days of school or work. Mortality was not associated with ITI, regardless of its success. Those with successful ITI had similar rates of treated bleeds, chronic pain, and health care use as those with no inhibitors. Undergoing ITI, particularly if successful, improved clinical outcomes but not mortality. These findings support decision making regarding initiation of ITI and inform future clinical trials.

Race, ethnicity, and immune tolerance induction in hemophilia A in the United States.

Background: In racially diverse communities, treatment of chronic diseases can vary across racial and ethnic groups. Objectives: To examine healthcare disparities in hemophilia care in the United States by evaluating receipt of immune tolerance induction (ITI) among different racial and ethnic groups. Methods: In this cross-sectional study, people with severe hemophilia A with an inhibitor who entered the Center for Disease Control and Prevention Community Counts registry between 2013 and 2017, were aged ≥5 years at study entry, and had a history of an inhibitor (n = 614) were included. The proportion of participants receiving ITI was examined according to race and ethnicity in bivariable analysis and multivariable analysis adjusting for demographic and clinical covariates. Unadjusted and adjusted prevalence ratios and corresponding 95% CIs were computed. Results: Among 614 participants included in the study, 56.4% were non-Hispanic (NH) White, 19.7% were NH Black, 18.4% were Hispanic, and 4.9% were Asian. ITI was received by 85.2% of participants. On bivariable analysis, ITI treatment did not vary by race or ethnicity. On multivariable analysis, NH Black and Hispanic participants were significantly less likely to receive ITI compared to NH White participants (adjusted prevalence ratio, 0.91 [95% CI, 0.84-0.99] and 0.84 [95% CI, 0.75-0.93], respectively). Conclusion: Although the role of ITI may evolve with growing use of emicizumab and the introduction of new hemophilia treatment products, understanding characteristics that influence care, particularly race and ethnicity, where physician bias and patient mistrust can occur, will remain relevant and applicable to other complex therapies, including gene therapy.