https://orcid.org/0000-0002-1144-8076
In this issue of Blood Global Hematology, Browne et al1 have demonstrated that hydroxyurea therapy reduces acute care utilization among patients with sickle cell disease (SCD) in Brazil, yet the expected cost savings did not materialize, highlighting the complex economics of chronic SCD care.
SCD is a chronic and disabling condition marked by acute vaso-occlusive crises and progressive end-organ damage. Hydroxyurea, one of the earliest and most widely adopted disease-modifying therapies, is proven to increase fetal hemoglobin, reduce painful episodes, reduce hospitalizations,2 reduce transfusion needs, and even improve survival. Evidence from high-income countries has consistently revealed reductions in health expenditures when hydroxyurea is used broadly and with adherence.3 The study by Browne et al offers a rare, large-scale cost analysis from a middle-income country, shedding light on the persistent challenges of implementing hydroxyurea in resource-constrained settings.4
The authors analyzed >3000 patients treated at a tertiary referral center in Rio de Janeiro.1 Only 1 in 5 received hydroxyurea, and fewer than 1 in 6 of those achieved adherence >50%. Patients on hydroxyurea had fewer emergency department visits and hospitalizations but significantly more ambulatory visits and higher overall costs. Laboratory monitoring, transfusion support, iron chelation, and chronic wound care emerged as substantial cost drivers. The study elegantly demonstrates that reducing acute utilization does not automatically equate to lowering total costs, particularly when adherence is low and chronic complications persist.
This finding is highly relevant for health systems across low- and middle-income countries. Although policymakers often focus on reducing costly acute events, the financial burden of SCD increasingly lies in long-term management. As patients live longer, expenses shift toward chronic care, which includes chelation for transfusional iron overload, management of stroke and renal complications, and treatment of refractory pain or leg ulcers. Hydroxyurea is critical but insufficient when introduced late in life or used inconsistently.
Several key messages emerge. First, early initiation of hydroxyurea, ideally in childhood, is crucial to prevent complications rather than simply mitigate them. Studies have revealed improved renal outcomes, neurocognition, and survival when therapy is started early and titrated to maximum tolerated dose. Second, adherence must be addressed. In this study, adherence was strikingly low. Barriers such as limited patient education, restricted access to laboratories, transportation challenges, and fragmented follow-up all contribute. Without strategies to improve adherence, cost-effectiveness cannot be realized. Third, comprehensive care must be expanded. Hydroxyurea reduces acute crises, but chronic complications require integrated approaches, including timely transfusion protocols, access to chelation, psychosocial support, and, increasingly, curative strategies such as transplantation or gene therapy.
The study also underscores an economic paradox: hydroxyurea shifts costs from emergency admissions to outpatient management, where expenses are less visible but remain substantial. This shift is not inherently negative; indeed, it reflects proactive care and investment in quality of life. However, policymakers must anticipate these costs and balance them against long-term gains in morbidity and mortality.
Ultimately, Browne et al highlight a fundamental truth: hydroxyurea is transformative for SCD, but its cost-saving potential depends on health system readiness, early initiation, sustained adherence, and integrated chronic care strategies. For Brazil and other middle-income settings, the challenge is not whether hydroxyurea works but on how to ensure its benefits extend beyond the emergency department and into lifelong, equitable, cost-effective care.
Conflict-of-interest disclosure: The author declares no competing financial interests.
