Efficacy and safety of early-start deferiprone in infants and young children with transfusion-dependent beta thalassemia: Evidence for iron shuttling to transferrin in a randomized, double-blind, placebo-controlled, clinical trial (START).

Autor: Elalfy MS; Department of Pediatric Hematology, Ain Shams University, Children's Hospital, Cairo, Egypt., Hamdy M; Research Center, Cairo University, Cairo, Egypt., Adly A; Department of Pediatric Hematology, Ain Shams University, Children's Hospital, Cairo, Egypt., Ebeid FSE; Department of Pediatric Hematology, Ain Shams University, Children's Hospital, Cairo, Egypt., Temin NT; Chiesi Canada Corporation, Toronto, Ontario, Canada., Rozova A; Chiesi Canada Corporation, Toronto, Ontario, Canada., Lee D; Chiesi Canada Corporation, Toronto, Ontario, Canada., Fradette C; Chiesi Canada Corporation, Toronto, Ontario, Canada., Tricta F; Chiesi Canada Corporation, Toronto, Ontario, Canada.
Jazyk: angličtina
Zdroj: American journal of hematology [Am J Hematol] 2023 Sep; Vol. 98 (9), pp. 1415-1424. Date of Electronic Publication: 2023 Jul 04.
DOI: 10.1002/ajh.27010
Abstrakt: Children with transfusion-dependent thalassemia (TDT) require regular blood transfusions that, without iron-chelation therapy, lead to iron-overload toxicities. Current practice delays chelation therapy (late-start) until reaching iron overload (serum ferritin ≥1000 μg/L) to minimize risks of iron-depletion. Deferiprone's distinct pharmacological properties, including iron-shuttling to transferrin, may reduce risks of iron depletion during mild-to-moderate iron loads and iron overload/toxicity in children with TDT. The early-start deferiprone (START) study evaluated the efficacy/safety of early-start deferiprone in infants/young children with TDT. Sixty-four infants/children recently diagnosed with beta-thalassemia and serum ferritin (SF) between 200 and 600 μg/L were randomly assigned 1:1 to receive deferiprone or placebo for 12 months or until reaching SF-threshold (≥1000 μg/L at two consecutive visits). Deferiprone was initiated at 25 mg/kg/day and increased to 50 mg/kg/day; some recipients' dosages increased to 75 mg/kg/day based on iron levels. The primary endpoint was the proportion of patients ≥SF-threshold by month 12. Monthly transferrin saturation (TSAT) assessment evaluated iron-shuttling. At baseline, there was no significant difference in mean age (deferiprone: 3.03 years, placebo: 2.63 years), SF (deferiprone: 513.8 μg/L, placebo: 451.7 μg/L), or TSAT (deferiprone: 47.98%, placebo: 43.43%) between groups. At month 12, there was no significant difference in growth or adverse event (AE) rates between groups. No deferiprone-treated patients were iron-depleted. At month 12, 66% of patients receiving deferiprone remained below SF threshold versus 39% of placebo (p = .045). Deferiprone-treated patients showed higher TSAT levels and reached ≥60% TSAT threshold faster. Early-start deferiprone was well-tolerated, not associated with iron depletion, and efficacious in reducing iron overload in infants/children with TDT. TSAT results provide the first clinical evidence of deferiprone shuttling iron to transferrin.
(© 2023 The Authors. American Journal of Hematology published by Wiley Periodicals LLC.)
Databáze: MEDLINE
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