Factors associated with hemoglobin response to hydroxyurea in patients with sickle cell disease

Chronic anemia is a hallmark of sickle cell disease (SCD) and contributes to morbidity and mortality. Pharmacological treatment options for chronic anemia in SCD are limited. Hydroxyurea (HU) remains the gold standard SCD treatment, but conflicting data exist regarding the impact of HU on hemoglobin (Hb) level. We conducted a longitudinal study of Hb response after HU initiation in a cohort of 82 patients with SCD. We found that the mean Hb level increased by 0.4 g/dL at 1 month and 0.3 g/dL at 3 months after HU initiation, compared with baseline. An Hb increase of ≥1 g/dL was observed in 26.3% of participants at 1 month and in 21.6% at 3 months. We also assessed the baseline demographic, clinical, and laboratory markers that were associated with Hb response after HU initiation using univariate linear regression and multivariate linear mixed-effects modeling. Lower baseline Hb, male sex, younger age, and less severe genotype were independently associated with greater Hb increase in response to HU. The effects of sex and genotype severity on Hb response were not evident in unadjusted analyses. Our results suggest that HU monotherapy is insufficient to address chronic anemia in many patients with SCD and highlight the need for combination therapy with HU to improve anemia-related outcomes. Our study also demonstrates the feasibility of using baseline data to guide therapy selection and create individualized treatment plans for patients with SCD.