Use of Chronic Blood Transfusion Therapies and Pharmaceutical Disease Modifying Treatments in Sickle Cell Disease: A Retrospective Cohort Analysis (2014-2021)
Authors: Newman Terri Victoria , Yang Jingye , Haubner Aaron , Anderson Melissa , Triulzi Darrell J , Novelli Enrico M 
Published: December 2024

Introduction
Numerous studies have shown that hydroxyurea and other newer pharmaceutical disease modifying treatments (pDMTs) are underutilized in sickle cell disease (SCD); however, the adoption of chronic blood transfusion therapy (CBT) as a preventive disease modifying therapy has been underexplored. Previous real-world analyses of CBT have focused on pediatric populations with limited follow-up or observation in adult populations. Given that the treatment paradigm in SCD continues to change, it is important to understand the application of CBT in the management of individuals with SCD. In this study, we aimed to explore factors and temporal patterns of disease modifying therapy approaches (CBT and pDMT) in a national cohort of SCD patients.
Methods
We conducted a retrospective cohort analysis of prescription and medical claims data from Optum's de-identified Clinformatics® Data Mart Database (CDM) from January 2014 to September 2021 in patients with SCD. Clinformatics® includes data on Commercial and Medicare insurance beneficiaries. CBT use was defined as 6 or more outpatient claims for blood transfusions (including simple and exchange) within a 1-year period, using qualifying transfusion codes. pDMT use was defined as at least 1 prescription fill for hydroxyurea, crizanlizumab, l-glutamine, or voxelotor. We defined 4 mutually exclusive treatment groups: pDMT use alone; combined pDMT and CBT use; CBT use alone; and no CBT or pDMT use. We conducted multinomial logistic regression analyses to identify clinical and sociodemographic factors associated with each treatment group. Then, we identified the yearly proportion of individuals receiving CBT or pDMT from 2014-2021.
Results
We identified 4,100 individuals with SCD. Of these, 1069 (26%) were in the pDMT user group, 119 (3%) in the CBT user group, 42 (1%) in the pDMT and CBT user group, and 2870 (70%) in the no CBT or pDMT user group. Multinomial analyses showed that compared to individuals under 18, those aged 31-54 and 55+ had a 38% (OR 0.62, 95% CI 0.50-0.78, p &lt; 0.01) and 64% (OR 0.36, 95% CI 0.27-0.47, p &lt; 0.01) lower odds of using pDMT only, respectively. These same age groups had 56% (OR 0.44, 95% CI 0.25-0.76, p &lt;0.01) and 80% (OR 0.20, 95% CI 0.10-0.40, p&lt;0.01) lower odds of using CBT. Men had 30% higher odds (OR 1.30, 95% CI 1.11-1.51, p &lt;0.01) of using pDMT and 115% higher odds (OR 2.15, 95% CI 1.13-4.10, p=0.02) of receiving combined pDMT and CBT compared to women. Individuals with a history of vaso-occlusive events had higher odds of using pDMT (OR 2.81, 95% CI 2.36-3.36, p&lt;0.01), CBT (OR 2.67, 95% CI 1.73-4.13, p &lt;0.01) or both pDMT and CBT (OR 3.14, 95% CI 1.48-6.67, p &lt;0.01). Those with severe organ complications (i.e., avascular necrosis, stroke, renal disease) had higher odds of using CBT (OR 2.10, 95% CI 1.26-3.50, p &lt;0.01) and both pDMT and CBT (OR 3.12, 95% CI 1.46-6.66, p&lt;0.01). Similar patterns were observed in individuals with thrombosis or pulmonary complications: higher odds of using CBT (OR 1.79, 95% CI 1.16-2.77, p=0.01) and combined pDMT and CBT (OR 2.17, 95% CI 1.09-4.31, p=0.03). Lastly, pDMT use modestly increased from 20.4% (321/1577) in 2014 to 28.5% (684/2398) in 2021* whereas CBT use sharply declined from 3.4% (54/1577) in 2014 to 0.6% (14/2398) in 2021*.
Conclusion
A higher proportion of SCD beneficiaries used pDMTs as preventive therapies compared to CBT, however, preventive therapeutic utilization remained low across all modalities. Over a 7-year period, pDMT use modestly increased by 8% while CBT use sharply declined after 2020, possibly owing to the impact of the COVID-19 pandemic on blood supply and healthcare resource utilization. Age, gender, and health disparities exist in the utilization of these treatments as older adults were less likely to use pDMTs or receive CBTs and women were less likely to receive pDMTs and combined pDMT + CBT. CBT with or without pDMTs were utilized more often by those with documented, severe organ complications possibly reflecting the need for more aggressive therapy in these subpopulations. Our study points to the importance of continuing to address disease modifying treatment use in SCD as substantial concerns remain about their utilization, particularly in relation to ongoing health disparities.
*Please note that the claims data for 2021 only include information up to September.