Trends of Disease Modifying Treatment Use in Sickle Cell Disease: Retrospective Analysis of Claims Data, 2014-2020

Introduction Over the last few years, several disease modifying treatments (DMTs) have received approval for the treatment of sickle cell disease (SCD). DMTs target key aspects of the pathophysiological processes of SCD and can reduce disease progression and morbidity. Prior to 2017, hydroxyurea was the only FDA-approved pharmacological DMT. After decades of limited pharmacologic options, three novel therapeutics have become available: L-glutamine, voxelotor, and crizanlizumab-tmca. However, data on real-world use of contemporary DMTs are limited to single centers, small sample sizes, and usually focus on single DMTs. Investigating the uptake of new DMTs in SCD is important as patients with SCD continue to experience high morbidity and mortality and, therefore, aggressive adoption of new treatments is paramount to improve patient outcomes. This study uses claims data from a large national insurer to provide information on treatment patterns for all four DMTs from 2014-2020.

Methods We conducted a retrospective cohort study using de-identified prescription and medical claims data from the Optum's Clinformatics Data Mart Database (Eden Prairie, MN) from January 2014 - September 2020. Optum contains information on commercial and Medicare insurance beneficiaries. We identified SCD individuals as those with a qualifying ICD-9/10 diagnosis code for SCD in the inpatient or outpatient setting within the study timeframe (index date).We required 6 months of continuous enrollment prior to the index date to collect patient characteristics. Outcomes evaluated were rates of DMT use per year for all DMTs and by each individual DMT. Rates of DMT use were calculated as the number of SCD individuals with at least one prescription fill for the respective DMT divided by total number of SCD individuals in the given year. We also evaluated sociodemographic and clinical characteristics .

Results A total of 5,688 individuals had a diagnosis of SCD between 2014-2020. In our cohort, 21.8% of individuals were less than 18 years of age, while 43.1% were between 18-45 years old. During the study period, we identified 1,933 individuals who had at least one prescription fill for any DMT and 3,755 individuals who had no fill for any DMT. Descriptive analyses of patient characteristics revealed that compared to non-DMT users, DMT users were more likely to be male (45.9% vs 40.5%), to be aged 18-45 (50.1% vs 39.5% ), have a higher number of pain episodes (4.1 vs 2.3), and a greater number of SCD complications such as acute chest syndrome (9.1% vs. 3.3%) and avascular necrosis (9.7% vs. 3.0%). For healthcare utilization, DMT users were more likely to have emergency department (ED) visits and inpatient hospitalizations compared to non-DMT users (7.0% vs. 3.7%; 12.1% vs. 8.1% respectively). However, non-DMT users were more likely to have outpatient visits (13.4% vs. 12.5%). When evaluating trends in treatment use, the overall use of DMTs has remained stable with a modest increase over the last 6 years. Analysis of individual DMT use patterns revealed that hydroxyurea use followed the same pattern. Newer DMTs were used in less than 5% of the population with a slight increase in rate of use over the years after approval.

Conclusion DMT users had a higher prevalence of SCD complications, pain crises, inpatient hospitalizations and ED visits, which likely reflects indication bias, and were more likely to be young adults, possibly because of concerns over poorer tolerability in older patients. Overall, in spite of the availability of newer DMTs since 2017, the overall rate of DMT use has remained largely stable with only modest increases. As expected, the most commonly used DMT was hydroxyurea, however, <30% of SCD individuals used hydroxyurea over the last 6 years, which confirms prior data showing that hydroxyurea is under prescribed and underutilized in SCD. Lack of guidelines with respect to the newer DMTs may have hampered more widespread adoption of these drugs, alongside knowledge gaps regarding their mechanism of action and place in therapy. In addition, the high cost of the new DMTs and lack of payer approval may have also been a factor in their poor uptake. These data point to the importance of educating health care providers and patients about the importance of pharmacologic DMTs in SCD, and of addressing all potential barriers to their utilization.

Kane-Gill:NIDDK: Research Funding; NCCIH: Research Funding; Society of Critical Care medicine: Membership on an entity's Board of Directors or advisory committees.