Iron chelation monotherapy in transfusion-dependent beta-thalassemia major patients: a comparative study of deferasirox and deferoxamine

Abstract

IntroductionIron overload is the primary cause of mortality and morbidity in thalassemia major (TM) despite advances in chelation therapy. The aim of this study was to compare the effectiveness and safety of deferasirox (DFX) and deferoxamine (DFO) as iron-chelating agents in patients with transfusion-dependent β-thalassemia major.MethodsThis prospective randomized study included 60 patients with transfusion-dependent β-TM during the period from September 2014 to September 2015. Their ages were ≥ 6 years, and they had serum ferritin above 1500 μg/L and were on irregular DFO therapy. Patients had regular packed red cell transfusion in a dose of 10 mL/kg/session. They were randomized to receive DFX (single oral daily dose of 20–40 mg/kg/day) or DFO (20–50 mg/kg/day via subcutaneous infusion over 8–10 hours, 5 days a week). Iron overload was determined by serum ferritin level. The primary endpoint was decrease of serum ferritin level below 1500 μg/L. The secondary endpoint was drug safety.ResultsBoth drugs significantly reduced serum ferritin (p < 0.001). At the end of follow-up, there were no significant differences between the two groups in serum ferritin levels (p = 0.673) and in percent reduction of ferritin (p = 0.315). There were no significant differences between the two groups in the total amount of blood transfusion (p = 0.166) and average iron intake (p = 0.227). There were no mortalities or any serious adverse effects, neutropenia, arthropathy, or pulmonary toxicity. Gastrointestinal upset and skin rash occurred more frequently with DFX than with DFO (p = 0.254 and 0.095, respectively).ConclusionWith appropriate dosing and compliance with drugs, both DFX and DFO are generally well tolerated, safe, and effective in reducing serum ferritin levels in iron-overloaded, regularly-transfused thalassemia major patients. Therefore, oral DFX is recommended for more convenience and adherence to the treatment regimen.

Interventions for improving adherence to iron chelation therapy in people with sickle cell disease or thalassaemia

“…Ten were multicentre trials (Calvaruso 2015; Elalfy 2015; Galanello 2006; Maggio 2009; Olivieri 1997; Pennell 2006; Pennell 2014; Taher 2017; Tanner 2007; Vichinsky 2007) and ranged from two centres in one country (Calvaruso 2015; Elalfy 2015; Olivieri 1997) to 44 centres in multiple countries (Vichinsky 2007). Six were single-centre trials (Aydinok 2007; Bahnasawy 2017; Badawy 2010; El Beshlawy 2008; Hassan 2016, Mourad 2003).…”

Effectiveness and Safety of Deferasirox in Thalassemia with Iron Overload: A Meta-Analysis

“…Six articles reporting RCTs with a total of 1,102 included patients were eligible for inclusion in the current meta-analysis. Among them, 2 studies were from Italy [16] and Egypt [17], respectively, while the remaining 4 were multicenter trials [18-21]. The baseline characteristics of the included studies are summarized in Table 1.…”

“…Double-blinding was mentioned in 4 RCTs [16, 18-20], and the blinding methods used were described. Meanwhile, 2 RCTs used an open-label design [17, 21]. Incomplete outcome data were reported in 2 RCTs [19, 20], and 1 study [20] revealed a withdrawal rate of more than 20%.…”

“…No specific data were found in Piga et al [16]. Two trials by Cappellini et al [21] and Hassan and Tolba [17] provided detailed data. In Cappellini et al’s trial, 4 DFX treatment subgroups (5, 10, 20, and 30 mg/kg/day) were assessed, and Hassan and Tolba’s average DFX dose approximated 30 mg/kg/day, which was more effective than DFO in reducing SF levels (MD –16.13, 95% CI –103.91 to 71.65, p < 0.01), especially in the high-dose group (30 mg/kg/day) (Fig.…”

“…Hassan and Tolba [17] also reported different types of drug-related AEs, but not in a systematic way. However, none of the 6 reports discussed neutropenia or agranulocytosis.…”