How the withdrawal of an essential therapy impacted acute care needs and highlighted delays in prescription switches
More than 100,000 people in the U.S. live with sickle cell disease, a condition marked by unpredictable pain, frequent emergency department (ED) visits, and a lifelong need for coordinated, reliable care. For many patients, disease-modifying therapies play a central role in reducing vaso-occlusive crises (VOCs) and helping to prevent the organ damage that can occur over time.
A growing range of disease-modifying and curative options has emerged over the past decade: hydroxyurea, the gold standard; newer oral treatments; monoclonal antibodies; and, most recently, gene therapy approaches. While these treatments have expanded choice and improved outcomes for many, the ecosystem remains fragile: Even a single therapy coming off the market can reverberate among patients and providers who depend on having reliable, continuous access to care. In December 2024, for example, voxelotor, once considered a breakthrough treatment option, was withdrawn from the market, causing thousands of patients and clinicians to urgently rethink care plans.
Drug transitions can be difficult to recognize in traditional datasets, but they matter deeply for understanding both patient stability and health-system strain. Using Komodo’s Healthcare Map®, which encompasses real-world insights from over 330 million patient healthcare journeys, and the rapid analysis capabilities of our AI agent, Marmot™, we examined how patients moved through this transition: how their acute-care needs shifted; which therapies they turned to next; and where important gaps emerged along the way.
We identified a cohort of over 4,400 patients receiving voxelotor at the time of its withdrawal. Approximately 88% were Black or African American, which reflects the typical racial distribution of sickle cell disease. Patients receiving the therapy were concentrated in the 35-44 and 25-34 age groups, representing the largest proportions.
The majority of treated patients were publicly insured, and a slightly larger proportion of treated patients were female.
- Approximately 74% of our treated cohort were insured through Medicaid or Medicare; 25% had commercial coverage.
- While sickle cell disease had a near-equal sex distribution, 56% of our treatment population were women, which suggests that women often exhibit higher outpatient healthcare utilization than men.
Emergency healthcare utilization declined in the six months after withdrawal compared with the six months before.
- VOC events fell by 37%.
- ED visits (overall and disease-related) fell by 21%.
- Overall and disease-related hospitalizations fell by 29% and 21%, respectively.
Nearly half of patients experienced long treatment gaps after stopping treatment with voxelotor.
Almost 49% of patients went more than 90 days without initiating another treatment. About 41% had no observed switch to any alternative therapy, indicating substantial delays or disengagement in disease-modifying care following discontinuation.
Among those who did switch therapies, hydroxyurea overwhelmingly dominated as the next-line option.
Roughly 82% of patients who initiated another therapy started hydroxyurea, which has been in use for decades as the primary evidence-based treatment for reducing VOCs and improving clinical outcomes. In contrast, only small proportions transitioned to transfusion-only care (10%) with no reported drug therapy, glutamine (7%), crizanlizumab (<1%), or gene therapy (<1%), underscoring limited uptake of newer or higher-intensity alternatives in this transition period.
This pattern underscores how, despite meaningful innovation in recent years, hydroxyurea remains the backbone of sickle cell disease treatment. It is widely accessible, deeply familiar to clinicians, and often the most feasible option during periods of therapeutic uncertainty. The reductions in VOCs, ED visits, and hospitalizations following treatment discontinuation align with the clinical concerns that originally prompted scrutiny of the therapy’s safety profile. But the broader utilization patterns point to system-level factors shaping the transition off of treatment. With roughly three-quarters of patients insured through Medicaid or Medicare, common barriers associated with public coverage, such as limited specialist availability, authorization requirements, and fragmented care pathways, likely contributed to the prolonged gaps in care we observed. The fact that nearly half of patients experienced delays that exceeded 90 days and 41% did not start any new therapy highlights how disruptions in the treatment landscape can exacerbate longstanding access challenges in sickle cell care.
Real-world data allows us to see those disruptions the way patients live them: through changes in crisis frequency, altered patterns of emergency care, and long pauses before restarting treatment. With tools like Marmot, these shifts become visible almost immediately and make it possible to understand where patients are losing continuity, where they’re adapting well, and where the system is failing to support them.
As innovation accelerates — and as the therapeutic landscape continues to evolve — having a real-time view of the patient journey becomes foundational to anticipating disruption, supporting clinicians, and ensuring that patients don’t fall through the cracks when the system shifts beneath them. By illuminating these patterns, healthcare systems can better anticipate challenges, minimize disruptions, and continue improving outcomes for patients living with sickle cell disease.
In a condition as demanding as sickle cell disease, the ability to follow the patient journey in real time isn’t just a measurement advantage — it’s essential for ensuring that care remains responsive, stable, and centered on the people who need it most.
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About Marmot: This analysis was conducted using Komodo Health’s Marmot, the first healthcare-native AI analytics platform, built on the industry’s most comprehensive real-world data and designed to deliver transparent, verifiable insights at unprecedented speed.
