Abstract

Importance

Despite hydroxyurea being an established treatment for sickle cell disease (SCD), it remains underused. The recent approval of the disease-modifying treatments (DMTs) l-glutamine, crizanlizumab, and voxelotor underscores the need to understand the uptake of DMTs in the current treatment landscape.

Objective

To explore characteristics that may be associated with DMT use and to describe observed patterns of yearly DMT use from 2014 to 2021.

Design, Setting, and Participants

This cross-sectional study used administrative claims data from Optum's deidentified Clinformatics Data Mart Database from January 1, 2014, to September 30, 2021, to identify adults and children with SCD. Data were analyzed from August 1, 2022, to August 28, 2023.

Exposure

Use of DMTs.

Main Outcomes and Measures

Patient characteristics across groups with varying patterns of DMT use and yearly patterns of prescription fills for hydroxyurea, crizanlizumab, voxelotor, and l-glutamine.

Results

A total of 5022 beneficiaries with SCD (2081 [41.4%] aged 18-45 years; 2929 [58.3%] female) were included in sample A (144 [2.9%] inconsistent users, 274 [5.5%] incident users, 892 [17.8%] consistent users, and 3712 [73.9%] non-DMT users). Inconsistent users had a higher prevalence of vaso-occlusive crises (mean [SD], 3.7 [4.7]), splenic complications (6 of 144 [4.2%]), pulmonary complications (36 of 144 [25.0%]), kidney disease (21 of 144 [14.6%]), acute chest syndrome (18 of 144 [12.5%]), and health care visits (eg, mean [SD] inpatient visits, 7.0 [10.7]) compared with the other use groups. Non-DMT users had the lowest prevalence of vaso-occlusive crises (mean [SD], 0.8 [2.4]), acute chest syndrome (109 of 3712 [2.9%]), and inpatient (mean [SD], 2.0 [6.6]) and emergency department (mean [SD], 0.7 [3.1]) visits and the highest proportion of adults 65 years and older (593 of 3712 [16.0%]). In sample B (6387 beneficiaries with SCD), hydroxyurea use modestly increased from 428 of 2188 participants (19.6%) in 2014 to 701 of 2880 (24.3%) in 2021. Use of l-glutamine increased briefly but gradually decreased 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, total DMT use increased from 428 of 2188 participants (19.6%) in 2014 to 815 of 2880 patients (28.3%) in 2021.

Conclusions and Relevance

In this cross-sectional analysis of adults and children with SCD, uptake of DMTs remained low from 2014 to 2021, despite the approval of newer therapies. Notable differences in patient characteristics across varied DMT exposure types necessitate further exploration into factors that facilitate DMT use and the creation of strategies to enhance DMT uptake.

MeSH

Cells, Cross-Sectional Studies, Anemia, Sickle Cell, Clinical Medicine, Prevalence, Acute Chest Syndrome, Therapeutics, Glutamine, Child, Hydroxyurea, Vaso-Occlusive Crises

Cited by

• Frequency of red blood cell allo-immunization in transfused patients with sickle cell disease in Africa: a systematic review with meta-analysis. Afr Health Sci, 2025
• Emergency Presentations of Pediatric Sickle Cell Disease in French Guiana. Diseases, 2025
• Opioid-related emergency admissions in people with opioid dependence/use disorder with and without sickle cell disease: An analysis of multi-state insurance claims. Gen Hosp Psychiatry, 2024
• Identifying and addressing underuse in hematologic care through systems-based hematology. Res Pract Thromb Haemost, 2025
• The Current Role of Hydroxyurea in the Treatment of Sickle Cell Anemia. J Clin Med, 2024
• Modulation of the allosteric and vasoregulatory arms of erythrocytic oxygen transport. Front Physiol, 2024
• Hospital Readmissions Among People With Sickle Cell Disease. JAMA Netw Open, 2025
• Economic burden of sickle cell disease in the United States: a retrospective analysis of a commercial insurance database. J Comp Eff Res, 2025