Hydroxyurea Reduces Pain Events in Very Young Children with Sickle-Cell Disease

Level 1: Likely reliable evidence

Painful symptoms of sickle-cell disease begin within the first year of life. Hydroxyurea (hydroxycarbamide) has been shown to reduce pain in adults (N Engl J Med. 1995;332:1317-1322) and has been associated with reduced hospitalization in school-age children (Pediatrics. 2008;122:1332-1342), but it has not previously been investigated in toddlers.

The BABY-HUG trial evaluated the effects of hydroxyurea in 193 children aged 9-18 months (Lancet. 2011; 377:1663-1672). Children with sickle-cell disease were randomized to hydroxyurea 20 mg/kg/day vs. placebo for two years.

The hydroxyurea group had significantly lower rates of pain events (177 events in 62 patients vs. 375 events in 75 patients, P=0.002) and dactylitis (24 events in 14 patients vs. 123 events in 42 patients, P <0.0001). Hydroxyurea was also associated with reduced gastroenteritis (P=0.001) and trends toward reductions in acute chest syndrome, transfusions and hospitalizations.

The risk of mild-moderate neutropenia was increased in the hydroxyurea group, but no other treatment-related adverse events were noted. There were no significant differences in the primary surrogate outcomes of splenic and renal function.