Comment: The quality of evidence is downgraded by imprecise results for some outcomes.
A Cochrane review included 17 studies. Eight randomised controlled trials were included, recruiting 899 adults and children with SCD (haemoglobin SS (HbSS), haemoglobin SC (HbSC) or haemoglobin Sβºthalassaemia (HbSβºthal) genotypes). Studies lasted from six to 30 months.
Four studies (577 adults and children with HbSS or HbSβºthal) compared hydroxyurea to placebo. There were statistically significant improvements in terms of pain alteration, measures of fetal haemoglobin and neutrophil counts and fewer occurrences of acute chest syndrome and blood transfusions in the hydroxyurea groups.
Two studies (254 children with HbSS or HbSβºthal also with risk of primary or secondary stroke) compared hydroxyurea and phlebotomy to transfusion and chelation; there were statistically significant improvements in terms of measures of fetal haemoglobin and neutrophil counts, but more occurrences of acute chest syndrome and infections in the hydroxyurea and phlebotomy group.
Of the remaining two studies, one (22 children with HbSS or HbSβºthal also at risk of stoke) compared hydroxyurea to observation; there were statistically significant improvements in terms of measures of fetal haemoglobin and neutrophil counts but no statistically significant differences in terms of adverse events (including serious or life-threatening events).
The final study (44 adults and children with HbSC) compared treatment regimens with and without hydroxyurea – there was statistically significant improvement in terms of measures of fetal haemoglobin, but no statistically significant differences in terms of adverse events (including serious or life-threatening events).
with a total of 324 subjects with sickle cell disease; 1 study with 299 adults (genotype SS) and 1 study with 25 children (genotype SS). From the data provided in the published reports, only the adult study could be analyzed. The study lasted 2 years and included adults who had reported more than 3 painful crises to treating physician in the preceding 12 months and who had <15% HbA. This study showed marked differences in favour of hydroxyurea treatment as compared with placebo in terms of annual crisis rate (the average crisis rate was 5.1 in the treated group and 7.9 in the placebo group, MD -2.80, 95% CI -4.74 to -0.86), use of transfusions (RR 0.67, 95% CI 0.52 to 0.87), and life-threatening complications (in particular, acute sickle chest syndrome: RR 0.44, 95% CI 0.28 to 0.68). Both studies documented the expected rise in fetal haemoglobin. No serious adverse effects were reported from either study.