Low Uptake of FDA-Approved Medications for Sickle Cell Disease Amongst the Adult Medicaid Population in North Carolina

Introduction

After decades in which hydroxyurea (HU) was the only FDA-approved medication for sickle cell disease (SCD), there has been a remarkable expansion of therapies, with FDA approval of L-glutamine (2017), crizanlizumab (2019) and voxelotor (2019). However, little is known about uptake of these medications on a population level, as most existing data come from cohort studies of patients at academic centers. One study analyzed national private insurance claims and observed an HU uptake of approximately 30% among all adults with SCD, compared with 2-3% for the recently approved therapies. However, it is unclear if those rates are representative of the SCD population at large, given that most people with SCD are insured by Medicaid, nor is it known how access to hematology care relates to medication uptake.

Methods

We conducted a retrospective, annual cross-sectional analysis of North Carolina Medicaid claims data from 2018 to 2022. Adults with SCD were identified as individuals age ≥18 years each year and with ≥3 encounters with an ICD-10 diagnostic code for SCD over the 5-year period. Individuals not continuously enrolled in Medicaid each year were excluded from analysis that year. Annual medication uptake was measured as ≥1 claim for a given medication (HU, L-glutamine, voxelotor, crizanlizumab, any opioid analgesic) within a calendar year. Encounters with a hematologist were identified using NPI taxonomy codes. Annual uptake was examined for the whole cohort and subgroups of interest, including those who did vs. did not see a hematologist each year, and those identified as homozygous sickle cell anemia (SCA) genotype by ICD-10 code. A binomial mixed effects model examined associations between medication uptake and hematology encounters, SCA genotype, and sociodemographic characteristics.

Results

There were 2,280 adults with SCD across the 5-year period; 2,170 had at least one year of continuous Medicaid enrollment and were included in analyses. They accumulated 8,424 person-years, ranging from n = 1,523 in 2018 to n = 1,833 in 2022. Average age was 33.3 years, and the cohort was 61.0% female, 96.3% Black race, and 94.1% non-Hispanic ethnicity. In the full cohort, 3,076 person-years (36.5%) included at least one encounter with a hematologist. The SCA subgroup included 1,206 individuals and 4,665 person-years, of which 2,193 (47.0%) included a hematologist encounter.

Annual rates of uptake were low among all 4 therapies for sickle cell disease. HU annual uptake declined from 21.9% in 2018 to 19.2% in 2022. Annual uptake of L-glutamine, voxeletor, and crizanlizumab were <5.0% each year; L-glutamine declined over the 5-year period, while voxeletor and crizanlizumab increased. Annual uptake of opioid medications ranged from 42.3% in 2018 to 38.5% in 2022. In the SCA subgroup, annual uptake for HU ranged from 27.1 - 31.4%, and opioid analgesics ranged from 43.4 - 48.5%.

Among individuals who saw a hematologist in a given year, annual uptake rates were higher across all medications. As an example in 2022, uptake rates were higher among those who did vs. did not see a hematologist for HU (36.2% vs. 8.7%), L-glutamine (3.4% vs. 0.5%), voxeletor (9.0% vs. 1.6%), crizanlizumab (9.1% vs. 1.0%), and opioid analgesics (56.1% vs. 27.6%). In the SCA subgroup, uptake rates for those who did vs. did not see a hematologist in 2022 were also higher, highlighting HU (40.9% vs. 14.4%) and opioid analgesics (58.0% vs 30.6%). Also in the SCA subgroup, disease activity in people taking vs. not taking HU were greater (i.e. ED visits: 7.1 vs. 3.7; seen by hematologist: 68.0% vs. 38.1%; receiving opioid: 88.7% vs. 27.3%).

Binomial mixed effects model showed significant association between uptake of hydroxyurea and seeing a hematologist within that year (OR 6.4, CI 4.8 - 8.5), as well as age (OR 0.85, CI 0.83 - 0.88), male gender (OR 2.0, CI 1.1 - 3.7), and SCA genotype (OR 9.1, CI 5.0 - 16.5).

Discussion

Uptake of FDA-approved medications for SCD is very low. Hydroxyurea - which has the strongest evidence and forms the backbone of care for SCA in adults - had uptake of only 20%, and even in a population likely to be SCA, uptake was only ~30%. This contrasts with the two-fold higher uptake of opioid analgesics, which treat symptoms of SCD but do not alter comorbidity trajectory.

Among the subset of people with SCD who saw a hematologist, uptake rates were markedly higher, and this increase was more pronounced for FDA-approved therapies than for opioids.

Little:NASCC: Membership on an entity's Board of Directors or advisory committees; Novo-Nordisk: Other: Adjusications Committee; Beam: Other: Research support directly and indirectly (through NASCC); Pfizer: Other: Research support directly and indirectly (through NASCC); Novartis: Other: Research support directly and indirectly (through NASCC); ASH: Research Funding; NHLBI: Honoraria, Research Funding.