The European Sickle Cell Disease Cohort - Hydroxyurea (ESCORT-HU) study was initiated when HU got an approval in SCD in Europe. This non-interventional prospective cohort study conducted in patients treated with HU according to current clinical practice with SCD was terminated in 2019 after enrolment of 1906 patients in 4 European countries. The main objective was to refine the safety profile of hydroxycarbamide, as well as to identify unexpected toxicities, especially after long-term treatment.
However clinical effectiveness evaluated by recording painful crises lasting more than 48 hours, episodes of ACS, number of hospitalisations related to SCD, and biological parameters were also regularly recorded according to the frequency of the hospital visits.
At inclusion, 926 (48.7%) patients had been previously treated off the label with HU (as HU was only approved for myeloproliferative disorders at the time), with mean duration of HU treatment of 5.74 ± 4.98 years. The mean age of this subgroup was 27.60 ± 14.81 years compared to 19.75 ± 15.79 years of the patients never been treated with HU before enrolment Of the 926 patients, 299 (32%) were younger than 18 years.
As showed in the table 1, hemoglobin level remains unchanged during the first two years but the HbF% increased in the HU-pretreated subgroup. In the "HU-naïve group", despite lower baseline Hb level et HbF% at baseline , similar outcome were obtained after 12 or 24 months. In terms of clinical outcomes, after 1 year of treatment the number of vaso-occlusive crises (VOC), acute chest syndrome (ACS) or hospitalizations decreased dramatically (table 2) in both group.
The median duration of follow-up in the cohort was 45 months (0-128). 123.7 ± 62.7 months was the mean total exposure to HU in the HU-pretreated subgroup. In term of safety, neutropenia, thrombocytopenia and dry skin were the most frequent HU- related adverse events reported but with comparable cumulated incidence between the HU-pretreated subgroup and HU-naïve subgroup (Table 3).
Conclusion: In real life setting, a significant improvement of the vasoocclusive symptoms was observed. Improvement of the compliance thanks to a treatment dedicated to the disease is probably one reason for better effectiveness; as suggested bythe lower red blood cell MCV was lower than expected at baseline in patients previously treated with HU. It is also possible that the increase in HbF% observed during the treatment could be another reason for clinical benefit. Paule and al (2011) demonstrated that daily regimen of HU were superior to weekly regimen. The fine tuning of the daily dose possible with HU tablets might be another reason of clinical optimization.
Galactéros:Addmedica:Membership on an entity's Board of Directors or advisory committees.Voskaridou:BMS:Consultancy, Research Funding;ADDMEDICA Company:Consultancy, Research Funding;NOVARTIS Company:Research Funding;GENESIS Company:Consultancy, Research Funding;PROTAGONIST Company:Research Funding;ACCELERON Company:Consultancy, Research Funding.Habibi:Pfizer:Consultancy;Bluebird:Consultancy;Novartis:Consultancy;Addmedica:Consultancy.De Montalembert:bluebird bio:Honoraria, Membership on an entity's Board of Directors or advisory committees;Vertex:Honoraria, Membership on an entity's Board of Directors or advisory committees;Addmedica:Honoraria, Membership on an entity's Board of Directors or advisory committees;Novartis:Honoraria, Membership on an entity's Board of Directors or advisory committees.
