S120: RANDOMIZED CONTROLLED TRIAL OF THE EFFICACY AND SAFETY OF DEFERIPRONE: SUBGROUP ANALYSIS OF PEDIATRIC PATIENTS IN IRON-OVERLOADED PATIENTS WITH SICKLE CELL DISEASE AND OTHER ANEMIAS
Notice bibliographique
Résumé
Background: Children with sickle cell disease (SCD) managed with blood transfusions often require iron chelation therapy to prevent iron overload.1 Deferoxamine (DFO) is an iron chelator approved for pediatrics that is often infused; however, adherence is a key challenge due to the burdensome route of administration.2 Deferiprone (DFP), an oral iron chelator, is a first-line treatment for transfusional iron overload in children and adults with SCD and other anemias.3 DFP is noninferior to DFO in SCD with iron overload (evaluated by liver iron concentration [LIC]) and has an acceptable safety profile.4 This subgroup analysis of FIRST (NCT02041299) assessed whether efficacy and safety of DFP were comparable to DFO in children with SCD. Methods: In this phase 4 open-label study, patients were randomized 2:1 to DFP or DFO for 12 months. The subgroup analysis included children (2–16 years of age) with SCD or another rare anemia treated for transfusional iron overload. Children received either oral DFP three times a day or subcutaneous DFO infusion 5–7 days a week. Iron load was monitored and dosage adjustments were allowed. The primary endpoint was change in LIC from baseline to month 12. Data were analyzed for all patients with a baseline and a follow-up LIC assessment (efficacy population). Safety assessments were done for all patients who received at least 1 dose of study drug (safety population). All patients provided informed consent or assent. Results: Of 228 patients in the safety population, 128 (DFP, n=86; DFO, n=42) were children. Most children (DFP, 75.6%; DFO, 80.9%) had a primary diagnosis of SCD (HbS). Mean ages (SD) in the DFP and DFO groups were 9.9 (3.7) and 10.9 (3.0) years (P=0.09), respectively. There were no significant differences between the DFP and DFO groups in sex (males, 59.3% vs 57.1%; P=0.85), ethnicity (P=0.68), or race (P=0.34). 5 children withdrew due to AEs (all DFP) and 19 withdrew for other reasons (DFP, n=14; DFO, n=5). There was not a significant difference in number of withdraws between groups (P=0.23). Children treated with DFP or DFO showed no significant differences in overall incidence of AEs (P=0.77; including neutropenias [P=0.30]), severe AEs (P=0.10), serious AEs (P=0.16), or withdrawals due to AEs (P=0.17). A difference in overall incidence of nonserious AEs considered at least possibly related to DFP (59.3% vs 33.3%; P=0.01) was found. For AEs ≥5%: see Table 1. The only AE with a significantly higher rate with DFP vs DFO was elevated liver enzymes (P=0.03)—a known transient reaction to DFP typically resolving with continued DFP. There were no AEs observed with DFP that had not been previously reported. One child developed agranulocytosis during parvovirus infection, which resolved the following day; and children <6 years of age receiving DFP had a comparable safety profile to older children (6–16 years of age) receiving DFP. In the efficacy population, after 12 months, there was no significant difference in mean (SD) LIC change from baseline with DFP vs DFO (-3.39±4.24 mg/g vs -2.99±3.16 mg/g, respectively; P=0.57). Conclusions: This subgroup analysis of children receiving chronic transfusions for SCD or other anemias corroborates previous findings that DFP is comparable to DFO in reducing LIC. No new safety concerns were observed. These findings may benefit children and healthcare providers when considering effective iron chelation therapy that may also address treatment-adherence concerns.References 1. Stanley et al, Pediatr Blood Cancer 2016; 63:1414 2. Elalfy et al, Hematol Oncol Stem Cell Ther 2010; 3:174 3. Chiesi USA Inc, Ferriprox® (deferiprone) tablets, Prescribing Information. 2021 4. Kwiatkowski et al, Blood 2019; 134 (Supplement 1): 618.
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction distillée sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
Scores Codex et Gemma par catégorie
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,001 | 0,000 |
| Bibliométrie | 0,000 | 0,001 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,000 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule tête enseignante, pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».