Underutilization of Disease-Modifying Therapies in Sickle Cell Disease: A Real-World Analysis from the ASH Research Collaborative Data Hub

Background

The underutilization of disease-modifying therapies (DMTs) in patients with sickle cell disease (SCD) is a serious deficiency in healthcare. Existing data on DMT use are often derived from claims or insurance databases, focus primarily on hydroxyurea, or are limited by geographic region or to a single institution. The ASH Research Collaborative Data Hub offers a comprehensive, real-world perspective on DMT utilization among diverse SCD patients and is unrestricted by payer type, enabling a more accurate assessment of DMT utilization and identification of barriers to optimal therapy.

Methods

The ASH RC Sickle Cell Disease Data Hub is a real-world data resource incorporating electronic health records from 14 sites across the United States on patients with SCD. We analyzed data on all patients with an SCD diagnosis (all genotypes) within the Data Hub from 2015 to 2023. DMT use was defined as reported treatment with hydroxyurea, voxelotor, or L-glutamine for ≥90 days within a year. Transfusions were categorized as a DMT if six or more transfusions occurred in a single year. Crizanlizumab was not included due to insufficient data for reliable analysis. Additional validation is needed to understand crizanlizumab prescription pattern and documentation. DMT data, patients' demographics, geographic location, co-morbidities, hemoglobin, and healthcare utilization data were provided by ASH Data Hub. To assess the validity of our methodology, we conducted preliminary face validity assessment of our variables and results by comparing it to prior large database studies (Newman et al. JAMA 2023; Stettler et. JAMA 2015). Additional validations of the accuracy of our operational definitions are planned in a subset of the population. The views expressed in this abstract are solely of the authors and do not represent the opinion of the ASH Research Collaborative or the American Society of Hematology.

Results

A total of 22,793 patients with SCD (55.8% female, mean age at first contact 24.1 ± 19 years) were included from the ASH Data Hub (2015-2023), yielding 116,885 patient-years of follow-up. Genotype data were available for 37% of patients. Despite a modest increase in DMT use between 2015 and 2023, DMT use remains relatively low. Overall, 5,547 patients (24%) were prescribed one or more DMT. DMT utilization increased from 7.2% in 2015 to 19.8% in 2023, primarily driven by hydroxyurea (from 5.5% to 16.6%). The adoption of other DMTs was very low and stable since its approval (voxelotor 0.7% in 2020 to 1.6% in 2023 and L-glutamine 1.3% in 2018 to 1.2% in 2023). Three percent were prescribed 2 or more DMTs concomitantly. Patients prescribed DMTs were younger (22.6 vs 24.6 years), had increased acute care utilization (2.7 vs 1.4 mean ED visits/hospitalizations per year), higher total annual inpatient days (17.3 vs 10.8 mean days), and lower mean hemoglobin levels (8.8 vs 9.9 g/dL) compared to non-DMT users. Co-morbidity rates (priapism, CVA, thromboembolism, CKD) were higher in the DMT group. Geographic variation in DMT prescription rates was also notable (Southwest 15.4%, Southeast 17.4%, Midwest 18.5%, West 26.4%, Northeast 33%). Among individual DMTs, voxelotor users had the lowest hemoglobin concentrations while those on ≥2 DMTs had the highest care utilization, potentially reflecting respective drug indications.

Conclusion

A real-world analysis of the ASH Data Hub underscores the persistent and alarming underutilization of DMTs in SCD. Despite decades of established efficacy and safety, hydroxyurea remains significantly underused, and newer DMTs are rarely used. The correlation between DMT use and disease severity is more likely explained by the reactive use of DMTs in patients with increased disease severity, rather than ineffectiveness of DMTs in mitigating disease severity. Our results are in line with published results suggesting face validity. Additional validations are underway to ensure the accuracy and reliability of our findings. To further understand barriers to broad, preventive DMT use, ongoing analyses will examine the characteristic differences between patients prescribed DMTs stratified by consistency of use, age, and biomarkers of treatment responses, aiming to identify factors associated with successful treatment.

Niss:Pfizer: Consultancy. Quinn:Disc Medicine: Consultancy; Emmaus Medical: Research Funding; Aruvant: Research Funding; Hillhurst Biopharmaceuticals: Consultancy.