Trends of Opioid Prescribing and Vaso-Occlusive Crises in Sickle Cell Disease in the U.S. (2011-2023)
Authors: Xu Kevin Y , Newman Terri Victoria , McGill Lakeya S. , Novelli Enrico M , Hillery Cheryl , Buss Joanna L , Huang Ruizi , Salas Joanne , Dong Fanghong , Stwalley Dustin , Liu Shiyuan A , Scherrer Jeffrey , Brown Tashalee R , Park Taewoo , Larochelle Marc R , Grucza Richard A , Jonassaint Charles R. 
Published: December 2024

BACKGROUND: Opioid prescribing patterns for individuals with sickle cell disease (SCD) are poorly characterized, particularly across different insurance types and age groups. Prior studies have been limited by short time frames and a focus on privately insured populations, an important limitation given that most individuals living with SCD are publicly insured. To address this gap in research, we comprehensively evaluated patterns of opioid prescribing and related health care utilization in publicly and privately insured individuals with SCD over a 10+ year time period in the U.S.

METHODS: In this retrospective cohort study, we analyzed national data from individuals aged 1-64 years with a diagnosis of SCD in the Merative™ MarketScan® Multi-State Commercial and Medicaid Databases (2011-2023). Due to heterogeneity in the socioeconomic characteristics of Medicaid and commercial (private, employer-based) enrollees, we divided Medicaid and commercial enrollees into two separate cohorts for analyses. Outcome variables included age-adjusted monthly rates of outpatient opioid prescribing and vaso-occlusive crisis (VOC) admissions. We estimated trends in monthly opioid prescribing and VOC admission rates via joinpoint regressions, which can operate without prior specifications of where break points may occur and are therefore useful for hypothesis generation and examination of emerging evidence. The monthly percentage change (MPC) between trend-change points and the average monthly percentage change (AMPC) over the entire study period were calculated.

RESULTS: Our sample comprised of 45,726 individuals diagnosed with SCD (mean age=25.1 years, 39.7% male, 52.9% Medicaid). Approximately 60% had &gt;1 filled outpatient opioid prescription, and one-quarter filled prescriptions with &gt;28-day supply. About 50% had &gt;1 VOC admission during enrollment. Compared to commercial enrollees, Medicaid enrollees had a higher overall mean monthly rate of opioid prescribing (18.3 vs 14.0 per 100 people) and VOC admissions (16.6 vs. 8.2 per 100 people). Adults had higher overall mean monthly opioid prescribing rates than children and adolescents (1-12 years =5.06, 13-17 years=11.34, 18-27 years=21.02, 28-45 years=22.32, 46-64 years=20.53 per 100 people). Mean VOC admission rates were the highest in transition-age adults (1-12 years=6.18, 13-17 years=9.50, 18-27 years=20.22, 28-45 years=16.51, 46-64 years=6.8 per 100 people).

Both commercial and Medicaid enrollees experienced a significant decline in opioid prescribing from 2011 to 2022, evidenced by average monthly percentage changes of -0.27% (95% CI: -0.32%, -0.22%) and of -0.54% (-0.64%, 0.45%), respectively. For VOCs, the commercial cohort showed an average monthly increase of 0.14% in VOC admissions (0.10%, 0.19%), while the Medicaid cohort showed an overall decrease in VOC admissions over the study period (AMPC=-0.07% [-0.12%, -0.01%]).

Temporal trends revealed post-COVID-19 (2020-2023) increases in VOCs for both commercial (MPC=1.76% [1.48%, 2.15%]) and Medicaid (MPC=0.60% [0.11%, 1.58%]) cohorts. The post-COVID-19 increase in VOC admissions was accompanied by an increase in opioid prescribing, occurring in 2021 for the commercial cohort (MPC=0.56% [0.18%, 1.25%]) and in 2022 for the Medicaid cohort (MPC=7.17% [3.11%, 15.40%]). Post-COVID-19 increases in monthly VOC admissions particularly concentrated in the pediatric and young adult population across both the commercial (MPC=3.62% [2.72%, 4.92%] 1-12 years; MPC=2.30% [0.24%, 13.84%] 13-17 years; MPC=1.78% [0.40%, 2.67%] 18-27 years; MPC=2.77% [1.15%, 7.39%] 27-45 years; MPC=0.64% [0.53%, 0.76%] 46-64 years) and Medicaid cohorts (MPC=2.19% [1.56%, 3.13%] 1-12 years; MPC=0.95% [0.30%, 1.45%] 13-17 years; MPC=-0.17% [-0.30%, 0.07%] 18-27 years; MPC=0.04% [-0.12%, 0.28%] 28-45 years; MPC=-0.14% [-0.30%, -0.04%] 46-64 years).

DISCUSSION: Our study is one of the few analyses to comprehensively evaluate opioid prescribing patterns and healthcare utilization across both public and private payers for individuals with SCD. VOC admissions increased significantly in the last 10 years, particularly in children and adolescents after 2020. We did not see a clear association between decreasing rates of opioid prescribing and increasing VOC admissions, indicating more nuanced factors are contributing to increased VOC admissions across age groups and payer types.