Hydroxyurea (hydroxycarbamide) use in adults with haemoglobin SC disease: A real-world study in Quebec

Haemoglobin SC (HbSC) disease is the second most prevalent form of sickle cell disease, but evidence for hydroxyurea (hydroxycarbamide; HU) to prevent pain episodes was limited until the prospective identification of variables as outcomes for treatment (PIVOT) trial. To assess HU effectiveness and safety in adults with HbSC, we conducted a retrospective, single-centre, pre-post cohort study at the Centre hospitalier de l'Université de Montréal. Patients initiated HU between January 2010 and July 2025. Effectiveness analysis required ≥12 months of pre-HU follow-up; patients with shorter follow-up were included for the safety analysis only. The primary end-point was the change in the annual frequency of a vaso-occlusive crisis (VOC) composite (VOCC: VOC, acute chest syndrome, priapism, splenic/hepatic sequestration) from 12 months pre-HU to months 4-16 post-HU. Secondary end-points included adverse events (AEs), treatment effectiveness and reasons for HU discontinuation. Of 263 patients assessed, 110 were included in the safety analysis and 75 in the effectiveness analysis. HU reduced mean VOCC by 56% (0.57-0.25; Δ = -0.32 ± 0.84; 95% confidence interval [CI] [-0.51, -0.13]; p = 0.0015). Haematological AEs were mostly mild (thrombocytopenia, 32.7%; neutropenia, 23.6%; leucopenia, 20.9%); bilirubin elevations were the most frequent non-haematological AE (10.9%), all asymptomatic and without clinical hepatotoxicity. In conclusion, HU was associated with a meaningful reduction in VOCC and was generally well tolerated.