Background: Hydroxyurea is the only approved drug for treatment of sickle cell disease.
Objective: To synthesize the published literature on the efficacy, effectiveness, and toxicity of hydroxyurea when used in adults with sickle cell disease.
Data Sources: MEDLINE, EMBASE, TOXLine, and CINAHL were searched through 30 June 2007.
Study Selection: Randomized trials, observational studies, and case reports evaluating efficacy and toxicity of hydroxyurea in adults with sickle cell disease, and toxicity studies of hydroxyurea in other conditions that were published in English.
Data Extraction: Paired reviewers abstracted data on study design, patient characteristics, and outcomes sequentially and did quality assessments independently.
Data Synthesis: In the single randomized trial, the hemoglobin level was higher in hydroxyurea recipients than placebo recipients after 2 years (difference, 6 g/L), as was fetal hemoglobin (absolute difference, 3.2%). The median number of painful crises was 44% lower than in the placebo group. The 12 observational studies that enrolled adults reported a relative increase in fetal hemoglobin of 4% to 20% and a relative reduction in crisis rates by 68% to 84%. Hospital admissions declined by 18% to 32%. The evidence suggests that hydroxyurea may impair spermatogenesis. Limited evidence indicates that hydroxyurea treatment in adults with sickle cell disease is not associated with leukemia. Likewise, limited evidence suggests that hydroxyurea and leg ulcers are not associated in patients with sickle cell disease, and evidence is insufficient to estimate the risk for skin neoplasms, although these outcomes can be attributed to hydroxyurea in other conditions.
Limitation: Only English-language articles were included, and some studies were of lower quality.
Conclusion: Hydroxyurea has demonstrated efficacy in adults with sickle cell disease. The paucity of long-term studies limits conclusions about toxicity.