Interventions Needed to Increase DMT Uptake in Sickle Cell Disease

Uptake of disease-modifying therapies (DMTs) among patients with sickle cell disease (SCD) has been low between 2014 and 2021, suggesting that interventions to improve adoption need to consider individual patient characteristics, according to a recent study published in JAMA Network Open.¹

Although hydroxyurea has been available to patients with SCD since the 1980s,² its use remains low, despite it being the only pharmaceutical DMT available for use in SCD until 2017. Since then, 3 other DMTs (L-glutamine, crizanlizumab, and voxelotor) have been approved but remain underused. A previous survey revealed that less than 50% of patients with SCD reported using any DMTs within the previous month, indicating inadequate uptake.

This is the first cross-sectional study to conduct a comprehensive evaluation of DMT use since newer DMTs targeting SCD have become available.

The analysis leveraged claims data from Optum’s deidentified Clinformatics Data Mart Database from January 1, 2014, to September 30, 2021, to identify individuals with SCD. Data analysis took place from August 1, 2022, August 28, 2023. The researchers identified 2 sets of samples and applied different continuous enrollment criteria to address 2 main objectives: understanding baseline characteristics among groups using DMTs (sample A) and examining individual and overall DMT use over time (sample B). For inclusion, patients had to maintain continuous enrollment for a minimum of 6 months before and after the index date.

Overall, 5022 patients with SCD were included in sample A and 6387 were included in sample B. In sample A, 144 (2.9%) were inconsistent users of DMTs, 274 (5.5%) were incident DMT users, 892 (17.6%) were consistent users, and 3712 (73.9%) were nonusers of DMTs. In total, 41.4% (n = 2081) of the cohort was aged 18 to 45 years, and 1027 (20.5%) patients were younger than 18 years. Female patients comprised 58.3% of the cohort and the mean (SD) 6-month preindex vaso-occlusive crises (VOCs) count was 1.3 (3.1).

Users with inconsistent adherence to treatment exhibited higher prevalence rates of VOCs (mean [SD], 3.7 [4.7]), splenic complications (n = 6 of 144 [4.2%]), pulmonary complications (n = 36 of 144; 25.0%), kidney disease (n = 21 of 144; 14.6%), acute chest syndrome (n = 18 of 144; 12.5%), and health care visits (mean [SD] inpatient visits, 7.0 [10.7]) compared to other groups of users.

Nonusers of DMTs had the lowest prevalence of VOCs (mean [SD], 0.8 [2.4]), acute chest syndrome (n = 109 of 3712; 2.9%), and inpatient (mean [SD], 2.0 [6.6]) and emergency department (mean [SD], 0.7 [3.1]) visits. They also had the highest proportion of adults aged 65 years and older (n = 593 of 3712; 16.0%).

In sample B, the use of hydroxyurea moderately increased from 428 of 2188 participants (19.6%) in 2014 to 701 of 2880 (24.3%) in 2021. L-glutamine use experienced a brief increase but gradually declined throughout the study period.

In 2021, out of 2880 participants, 102 (3.5%) had at least 1 fill for crizanlizumab, and 131 (4.6%) had at least 1 fill for voxelotor. Overall DMT use increased from 19.6% in 2014 to 28.3% in 2021, driven by new treatments. However, less than 5% used newer DMTs, and nearly 75% received no DMT.

The researchers attributed the gaps in utilization to limited national awareness and funding, emphasizing the need to optimize DMT use. Barriers to usage, impact of disease severity, and initiation strategies require further exploration.

“To gain a more comprehensive understanding of DMT use, future analyses should link examinations of use over time with an exploration of the various patient-level, health system–level, and clinician-level factors or barriers that facilitate or impede DMT use. Additionally, as more research becomes available to guide the appropriate use of DMTs, it will be important to conduct further utilization studies to identify areas where intervention strategies can be deployed to improve the use of DMTs,” wrote the authors.

The study recognizes limitations, such as relying solely on prescription fill data without insight into actual medication use, lacking individual-level factors influencing eligibility for DMTs, and not including patients receiving Medicaid benefits.

The researchers concluded, “Our results underscore the importance of conducting additional research to understand and address barriers to DMT utilization. They also highlight the necessity of advocating for clinical and policy initiatives aimed at improving the development and use of DMTs within this population. Ultimately, increasing access to and use of DMTs has the potential to improve outcomes and quality of life for individuals with SCD.

Reference

1. Newman TV, Yang J, Suh K, et al. Use of disease-modifying treatments in patients with sickle cell disease. JAMA Netw Open. 2023;6(11):e2344546. doi:10.1001/jamanetworkopen.2023.44546

2. Hydroxyurea for sickle cell disease. American Society of Hematology. Accessed December 19, 2023. https://www.hematology.org/-/media/hematology/files/education/hydroxyurea-booklet.pdf