Most patients with sickle cell disease not prescribed disease-modifying therapy
Key takeaways:
- Researchers observed what they called “alarming” underutilization of disease-modifying therapies for sickle cell disease.
- More research is needed to explore the reasons for underutilization.
The underutilization of disease-modifying therapy by people with sickle cell disease is “persistent and alarming,” according to an analysis of real-world data.
The findings, presented in December at ASH Annual Meeting and Exposition, show this trend remains a “serious deficiency in health care,” Omar Niss, MD, director of classical hematology at Cincinnati Children’s Hospital Medical Center and a faculty member of the UC Department of Pediatrics, and colleagues concluded.
Niss and colleagues evaluated data on 22,793 patients (55.8% female; mean age at baseline, 24.1 ± 19 years) with sickle cell disease included in the ASH Data Hub between 2015 and 2023.
Researchers defined disease-modifying therapy use as reported treatment with hydroxyurea, voxelotor (Oxbryta, Global Blood Therapeutics) or L-glutamine for 90 or more days within a year.
About one-quarter (24%; n = 5,547) of the cohort received prescriptions for one or more disease-modifying therapies, and 3% received prescriptions for two or more therapies to be used in combination.
Thirty-nine percent of those with verified hemoglobin SS genotype — the most severe type of sickle cell disease — were prescribed disease-modifying therapy.
Overall, patients prescribed disease-modifying therapy were younger (22.6 years vs. 24.6 years), had increased acute care utilization (2.7 vs. 1.4 ED visits or hospitalizations per year), had a greater likelihood of in-patient hospitalization (17.3 vs. 10.8 days per year) and had lower levels of hemoglobin (8.8 g/dL vs. 9.8 g/dL) than those who had not been prescribed disease-modifying therapy.
Between 2015 and 2023, use of disease-modifying therapy increased from 7.2% to 19.8%. Greater use of hydroxyurea — which rose from 5.5% to 16.5% during the period — accounted for much of the increase.
Use of newer disease-modifying therapies was “very low and stable,” researchers wrote.
Voxelotor use increased from 0.7% in 2020 to 1.6% in 2023, and L-glutamine use declined slightly from 1.3% in 2018 to 1.2% in 2023. Voxeletor subsequently was withdrawn from the U.S. market in September 2024 due to safety concerns.
“Sickle cell disease is a very serious, genetic disease that is lethal if it is untreated. It affects all the organs in the body,” Niss told Healio. “We do have evidence that disease-modifying therapies not only improve day-to-day living by reducing pain and improving hemoglobin, but also protect against organ damage. By underusing them, we’re exposing our patients to potential harm.”
Healio spoke with Niss about the findings, the potential explanations for underutilization of disease-modifying therapies, and strategies that can be employed to increase use.
Healio: Prior to this study, what had been known about use of disease-modifying therapies in sickle cell disease?
Niss: There’s a large body of evidence about their efficacy and safety. One of the oldest medications, hydroxyurea, has been in use for close to 40 years, so we know these therapies are effective. We know they are safe, and they are highly recommended for patients with sickle cell disease.
Healio: What motivated you to analyze use of disease-modifying therapy use in a real-world population?
Niss: Several studies in the past few years showed use of these medications is fairly sparse compared with what we’d like it to be. However, these studies all have limitations. They may have included homogenous populations or looked at a specific insurance claim database, so they may have been limited in their patient populations. The ASH Data Hub is a comprehensive registry for patients with sickle cell disease. It encompasses patients from multiple institutions across the country and is not limited by insurance. It provides a good snapshot of the sickle cell disease population and the use of these medications.
Healio: What did you find?
Niss: Disease-modifying therapies are indeed underused, even in this large and representative sample. If we look at the registry overall — looking at all types of sickle cell disease severities and genotypes — the overall rate of use is about 21%, which is very low. If we dig deeper and look at the most severe form of sickle cell disease, hemoglobin SS, the utilization rate increased to 35%, but that is still very low. I can’t think of a reason a person with hemoglobin SS would not be on a disease-modifying therapy.
Healio: Did the findings surprise you?
Niss: Given what we already know from smaller studies, it’s not too shocking, but we were hoping to see an increase in disease-modifying therapy use over time when we looked at this larger and current sample. It’s more disappointing than surprising. We don’t yet have a good understanding of why these are underused, and we need to study that. There may be barriers to use — either on a systemic level, institutional level or patient level — that need to be delved into and understood.
Healio: What strategies can be implemented to address this problem?
Niss: We need to find ways to mitigate this problem but, to do that, we have to understand why this is happening. A large database like the ASH Data Hub could give us clues about how to approach this problem by helping us understand the factors associated with it. I suspect there won’t be a one-size fits-all solution. There are various factors and different barriers that need to be addressed, such as access to care, insurance problems or availability of physicians trained to treat sickle cell .
In addition to trying to understand the reasons for such low utilization, we’re also trying to validate the data we are generating from the ASH Data Hub. This is one of the earliest analyses of this database, so we need to be sure the numbers and the data we’re generating are meaningful and applicable. We’re doing some validations within the registry that we hope will increase confidence in our results.
References:
- Niss O, et al. Abstract 2312. Presented at: ASH Annual Meeting and Exposition; Dec. 7-10, 2024; San Diego.
- American Society of Hematology. Disease-modifying therapies remain underused in SCD despite safety and efficacy (press release). Available at: https://www.hematology.org/newsroom/press-releases/2024/disease-modifying-therapies-remain-underused-in-scd-despite-safety-and-efficacy. Published Dec. 7, 2024. Accessed Feb. 7, 2025.
For more information:
Omar Niss, MD, can be reached at omar.niss@cchmc.org.
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