Systematic literature review on hydroxyurea treatment of sickle cell disease in low- to Middle-income countries

Abstract Sickle cell disease (SCD) constitutes a substantial health concern with a global impact, affecting millions of individuals worldwide. Low- and middle-income countries (LMICs), especially those in sub-Saharan Africa and the Caribbean have the highest incidence and mortality rates. Currently, curative treatments for SCD are limited, while hydroxyurea (HU) has been the cornerstone for SCD therapy. This systematic literature review focused on the clinical efficacy, safety, and real-world effectiveness of HU treatment for SCD in LMICs. The literature search yielded 69 unique studies from LMICs. Among these 51 were observational studies and 18 had clinical trial design. The most common fixed dose of HU was 20 mg/kg/day across the studies. The maximum tolerated dose in clinical trials was 25 to 35 mg/kg/day in children aged <18 years and 30 mg/kg/day in real-world settings in both children (aged <18 years) and adults (aged >18 years). The treatment duration ranged from 0.25 to 15 years in the included studies. Published evidence highlights that HU was well tolerated and effective in improving hematological outcomes and reducing vaso-occlusive crisis–related pain, malaria events, and stroke risk in patients with SCD in sub-Saharan Africa. Hospitalization and mortality rates were reduced after HU treatment. These findings are consistent with current consensus guidelines to initiate HU treatment for patients with SCD, starting as early as 9 months of age. Implementation of effective strategies of HU into the existing health-care system will ensure proper utilization of HU to yield maximal therapeutic benefits in SCD management, thereby reducing SCD mortality in low-to-middle-income settings.