Sophie Lanzkron, MD; John J. Strouse, MD; Renee Wilson, MSc; Mary Catherine Beach, MD, MPH; Carlton Haywood, MA; HaeSong Park, MD, MPH; Catherine Witkop, MD, MPH; Eric B. Bass, MD, MPH; Jodi B. Segal, MD, MPH
Disclaimer: The authors of this report are responsible for its content. Statements in the report should not be construed as endorsements by the Agency for Healthcare Research and Quality or the U.S. Department of Health and Human Services.
Grant Support: This project was funded under contract no. 290-02-0018 from the Agency for Healthcare Research and Quality, U.S. Department of Health and Human Services.
Potential Financial Conflicts of Interest:Grants received: C. Haywood (National Institutes of Health [grant no. 5F31HL082037-03]).
Requests for Single Reprints: Sophie Lanzkron, MD, Johns Hopkins University, 1830 East Monument Street, Suite 7300, Baltimore, MD 21205.
Current Author Addresses: Drs. Lanzkron, Beach, Park, and Segal: Johns Hopkins University, 1830 East Monument Street, Baltimore, MD 21205.
Dr. Strouse: Johns Hopkins University, 720 Rutland Avenue, 1125 Ross, Baltimore, MD 21205.
Ms. Wilson: Johns Hopkins University, 1830 East Monument Street, Room 8061, Baltimore, MD 21287.
Mr. Haywood: The Johns Hopkins Institute of Bioethics, 100 North Charles Street, Suite 740, Baltimore, MD 21201.
Dr. Witkop: Johns Hopkins Bloomberg School of Public Health, 615 North Wolfe Street, Baltimore, MD 21205-2179.
Dr. Bass: Johns Hopkins University, 1830 East Monument Street, Room 8068, Baltimore, MD 21287.
Hydroxyurea is the only approved drug for treatment of sickle cell disease.
To synthesize the published literature on the efficacy, effectiveness, and toxicity of hydroxyurea when used in adults with sickle cell disease.
MEDLINE, EMBASE, TOXLine, and CINAHL were searched through 30 June 2007.
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.
Paired reviewers abstracted data on study design, patient characteristics, and outcomes sequentially and did quality assessments independently.
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.
Only English-language articles were included, and some studies were of lower quality.
Hydroxyurea has demonstrated efficacy in adults with sickle cell disease. The paucity of long-term studies limits conclusions about toxicity.
Study flow diagram.
RCT = randomized, controlled trial; SCD = sickle cell disease. *The evidence report provides details of the search strategies (7). †The reasons for exclusion exceed the total number of studies because reviewers could enter multiple reasons for exclusion. ‡89 studies were not included in this review because they included children or infants only or examined barriers only. Toxicity and efficacy studies in SCD overlap.
Table 1. Characteristics of RCTs and Observational Studies of HU for Treatment of SCD
Table 2. Outcomes of RCTs and Observational Studies of HU for Treatment for Sickle Cell Disease
Table 3. Toxicity Results in Studies of HU for Sickle Cell Disease
Table 4. Summary of the Evidence in Sickle Cell Disease
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Lanzkron S, Strouse JJ, Wilson R, Beach MC, Haywood C, Park H, et al. Systematic Review: Hydroxyurea for the Treatment of Adults with Sickle Cell Disease. Ann Intern Med. 2008;148:939–955. doi: 10.7326/0003-4819-148-12-200806170-00221
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Published: Ann Intern Med. 2008;148(12):939-955.
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