Introduction: Hemolysis in sickle cell disease (SCD) contributes to complications such as anemia, leg ulcers, and kidney dysfunction. Voxelotor, a hemoglobin S polymerization inhibitor was approved to reduce hemolysis and improve anemia in SCD. However, the manufacturer voluntarily withdrew the drug from the market on September 25, 2024, following data suggesting an imbalance in vaso-occlusive crises and fatal events. This study aims to evaluate the clinical impact of voxelotor discontinuation on adult SCD patients previously treated with the medication.

Methods: This retrospective study included 73 adults (≥18 years) with SCD who received care at the adult SCD clinic at the University of Illinois Chicago (UIC) and were prescribed voxelotor between November 25, 2019, and September 25, 2024. Data collected included voxelotor dispensing history, laboratory values, and the number of emergency department (ED) visits and hospitalizations in the 6 months before and after the drug withdrawal. Descriptive statistics, Chi-square test, and Wilcoxon signed-rank tests were used for paired comparisons. Mean ± standard error values are provided.

Results: Of the 73 patients prescribed voxelotor, 54 (74%) initiated therapy, and all were notified of the withdrawal by September 30, 2024. Among them, 32 patients (59%) were actively taking voxelotor at the time of withdrawal, with a median treatment duration of 20 months (IQR 5–36). In the 32-patient cohort, the median age of this cohort was 30 years; 21% were male, 69% had HbSS or HbSβ⁰ genotypes, and 44% were on concurrent hydroxyurea therapy. All but three patients underwent a tapering regimen, reducing the voxelotor dose from 1500 mg daily to 1000 mg for one week, then to 500 mg daily for another week before discontinuation. After discontinuation, hemoglobin levels significantly decreased from 8.2 ± 0.3 g/dL to 7.7 ± 0.3 g/dL (p=0.0041). When comparing healthcare utilization during the 6 months before and after voxelotor discontinuation, the total number of ED visits was 7 vs. 10, hospitalizations were 15 with no acute chest syndrome (ACS) vs. 15 with 2 ACS episodes, and blood transfusions were 9 vs. 13 units total among all 32 patients, respectively. None of these differences were statistically significant.

Conclusion: Despite the abrupt market withdrawal of voxelotor, patients were promptly notified. Discontinuation was associated with a noticeable decline in hemoglobin levels, though it did not lead to increased utilization of healthcare services such as blood transfusions, ED visits, or hospital admissions. These findings emphasize the necessity for careful monitoring of patients after the sudden discontinuation of disease-modifying therapies and highlight the importance of having accessible alternative treatments for managing severe anemia in SCD.

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2025
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