Real-World Study Identifies Gaps in Polycythemia Vera Management and Substantial Thromboembolic Costs

Key Clinical Summary:  

• A real-world study of 11 311 patients with polycythemia vera (PV) found that 50.9% experienced burdensome treatment requirements and/or thromboembolic events despite receiving standard-of-care treatment.
• Among patients with available hematocrit measurements, 85.3% had at least 1 reading of 45% or higher, suggesting persistent challenges with hematocrit control.
• Patients experiencing thromboembolic events incurred mean all-cause health care costs of $71 195 during the following 12 months, highlighting the economic burden of PV-related complications.

A large real-world study of patients with PV identified substantial gaps in disease management, including frequent therapeutic phlebotomy, inadequate hematocrit control, persistent symptoms, and thromboembolic complications associated with considerable health care expenditures.

The findings suggest that many patients continue to experience significant clinical and treatment burden despite receiving standard-of-care therapies, highlighting opportunities to improve disease monitoring, treatment optimization, and complication prevention.

Treatment Patterns Reveal Persistent Disease Burden

Researchers evaluated 11 311 patients with PV, including 5859 (51.8%) classified as high risk and 5452 (48.2%) classified as low risk.

High-risk patients were older than low-risk patients, with mean ages of 68.3 and 48.9 years, respectively. They also had a greater prevalence of cardiovascular risk factors (68.1% vs 53.0%) and a history of thromboembolic events before the index date (23.9%).

Treatment patterns varied across the population. Most patients (75.0%) received therapeutic phlebotomy alone, while 12.2% received hydroxyurea alone, 10.9% received both phlebotomy and hydroxyurea, and 1.9% received ruxolitinib or interferon.

Among patients receiving phlebotomy, 46.2% required frequent procedures. Additionally, 41.7% of patients receiving hydroxyurea were treated with high-dose regimens.

Overall, 50.9% of patients experienced burdensome treatment and/or thromboembolic events, defined by frequent phlebotomy, high-dose hydroxyurea, or an incident thromboembolic event.

This burden was observed across risk categories, affecting 52.6% of high-risk patients and 49.1% of low-risk patients.

Hematocrit Control Remains a Challenge

Hematocrit control is a central component of PV management, with maintaining levels below 45% an established treatment objective.

Among 1268 patients with at least 2 hematocrit measurements during follow-up, 85.3% had at least 1 measurement of 45% or higher. More than half (55.4%) had at least 1 hematocrit measurement of 50% or higher.

The proportion of patients with an average hematocrit level of at least 45% was 62.8% overall, including 55.2% of high-risk patients and 74.4% of low-risk patients. Hematocrit control also differed by treatment group.

Patients receiving phlebotomy alone had the highest proportion of uncontrolled hematocrit measurements, with 90.6% recording at least 1 value of 45% or higher and 72.1% having an average hematocrit level of at least 45%.

In comparison, the proportions with an average hematocrit level of at least 45% were 42.5% among patients receiving phlebotomy plus hydroxyurea, 25.0% among those receiving ruxolitinib or interferon, and 24.1% among those receiving hydroxyurea alone.

However, the researchers cautioned that treatment groups differed in baseline characteristics and disease severity. The findings therefore cannot establish that one treatment strategy provides superior hematocrit control.

Thromboembolic Events and Disease Progression Persist

During a mean follow-up of 3.6 years, 15.3% of patients experienced an incident thromboembolic event, 9.6% developed iron deficiency anemia, and 4.4% experienced disease progression.

High-risk patients had greater rates of thromboembolic events than low-risk patients (21.3% vs 9.0%), as well as higher rates of iron deficiency anemia (11.0% vs 8.0%) and disease progression (6.1% vs 2.6%).

Clinical outcomes also varied across treatment groups. Thromboembolic events occurred in 14.4% of patients receiving phlebotomy alone, 19.2% receiving hydroxyurea alone, 17.6% receiving phlebotomy plus hydroxyurea, and 14.2% receiving ruxolitinib or interferon.

The ruxolitinib/interferon group had the highest observed rate of disease progression at 34.9%, compared with rates ranging from 1.7% to 12.3% among the other treatment groups.

The investigators suggested that this difference may reflect more advanced or treatment-refractory disease among patients receiving these therapies rather than an effect of the treatments themselves.

Symptoms Remain Common Across Risk Groups

PV-related symptoms affected 83.2% of the overall study population, demonstrating that symptom burden remained substantial regardless of risk classification.

The most documented symptoms included:

• Difficulty sleeping (37.8%)
• Depression or anxiety (31.2%)
• Fatigue (29.9%)
• Anemia (28.1%)
• Abdominal pain (27.8%)
• Shortness of breath (23.8%)
• Bleeding (20.8%)

Although high-risk patients experienced greater rates of anemia, shortness of breath, and bleeding, low-risk patients had higher rates of difficulty sleeping and depression or anxiety.

Overall symptom prevalence was similar between high-risk and low-risk patients, at 83.8% and 82.6%, respectively.

These findings suggest that conventional risk stratification does not fully capture the symptom burden experienced by patients with PV.

Thromboembolic Events Associated With Substantial Health Care Costs

The study also evaluated the economic burden of thromboembolic complications.

Among 1159 patients who experienced an incident thromboembolic event and had at least 12 months of subsequent data, mean all-cause health care costs totaled $71 195 during the year following the event.

Approximately 29.2% of these expenditures were attributable to the initial thromboembolic event.

Nearly half of initial events (42.0%) required hospitalization, with an average hospital stay of approximately 7 days. Most initial thromboembolic events (75.0%) were arterial.

Mean all-cause costs during the 12-month post-event period were $68 332 among high-risk patients and $77 867 among low-risk patients.

These findings highlight the financial consequences of thromboembolic complications across PV risk groups, although the reported costs represent total health care spending during the follow-up period rather than costs exclusively attributable to PV or the thromboembolic event.

Implications for Managed Care

The findings identify several opportunities for managed care organizations to evaluate the effectiveness of existing PV management strategies.

First, the high prevalence of hematocrit measurements exceeding 45% suggests a need for continued monitoring and timely reassessment of treatment effectiveness. This may be particularly important among patients receiving phlebotomy alone, who demonstrated the highest rates of inadequate hematocrit control in the laboratory subset.

Second, the substantial symptom burden across both high-risk and low-risk populations suggests that disease management should extend beyond thromboembolic risk reduction to incorporate symptoms, quality of life, and treatment burden.

Third, the considerable expenditures observed following thromboembolic events highlight the potential economic importance of complication prevention.

that improve disease control and reduce thromboembolic risk could potentially reduce downstream health care utilization, although the study did not directly evaluate the cost-effectiveness of specific interventions.

The findings also underscore the importance of interpreting treatment comparisons cautiously. Differences in patient characteristics, disease severity, and treatment history may influence observed outcomes, and additional adjusted longitudinal analyses are needed to determine whether particular treatment strategies improve hematocrit control or reduce complications.

Conclusion

This real-world analysis identified persistent unmet needs in PV management, including inadequate hematocrit control, frequent treatment requirements, substantial symptom burden, and thromboembolic events associated with high health care costs.

With more than half of patients experiencing burdensome treatment and/or thromboembolic complications, the findings support continued efforts to optimize treatment strategies, improve monitoring, and address clinical and economic burdens across both high-risk and low-risk PV populations.

Reference

Gerds AT, Fan Q, Jerry M, et al. Disease burden, inadequate hematocrit control, and thromboembolic events in patients with polycythemia vera despite current standard of care treatment: a retrospective claims study. J Blood Med. 2026;22(17):626464. doi: 10.2147/JBM.S626464.